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Sample records for pyrimidine dimer formation

  1. Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

    Science.gov (United States)

    Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

    2017-09-01

    Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm(2)); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Pyrimidine dimer formation and germination of UV-irradiated spores of Dictyostelium discoideum NC-4 and. gamma. s-13

    Energy Technology Data Exchange (ETDEWEB)

    Nozu, K.; Ohnishi, T.; Okaichi, K. (Nara Medical Univ., Kashihara (Japan))

    1982-04-01

    Survival, UV-photoproducts and germination of UV-irradiated spores of Dictyostelium discoideum were studied on two strains, NC-4 and ..gamma..s-13. The spores of NC-4 are about 35 times more resistant to UV than ..gamma..s-13 spores at 10% survival. Pyrimidine dimers were formed in UV-irradiated spores in both strains. No photoproducts other than pyrimidine dimers were detected. The formation of pyrimidine dimers in spores was about 2% in both strains at 800 J/m/sup 2/. In the germination of spores, the conversion of spores into swollen spores was not affected by UV in both strains, but the emergence of amoebae from the swollen spores was suppressed, which was more distinctive in ..gamma..s-13 spores than in NC-4 spores. The emerged amoebae from the UV-irradiated NC-4 spores were viable, while those from the ..gamma..s-13 spores were inviable even when they succeeded in emergence.

  3. Biological consequences of cyclobutane pyrimidine dimers

    NARCIS (Netherlands)

    Vink, A.A.; Roza, L.

    2001-01-01

    In the skin many molecules may absorb ultraviolet (UV) radiation upon exposure. In particular, cellular DNA strongly absorbs shorter wavelength solar UV radiation, resulting in various types of DNA damage. Among the DNA photoproducts produced the cyclobutane pyrimidine dimers (CPDs) are predominant.

  4. [Retarded excision of pyrimidine dimers in human unstimulated lymphocytes].

    Science.gov (United States)

    Snopov, S A; Roza, L; de Gruijl, F R

    2006-01-01

    Using immuno-labelling of cyclobutane pyrimidine dimers (CPDs) in nuclei of peripheral lymphocytes after their UVC-irradiation and cultivation, we have found that within the first four hours of cultivation the CPD-specific fluorescent signal from cell nuclei increased. Earlier, a similar increase in binding of antibody specific for pyrimidine (6-4) pyrimidone photoproducts to undenatured DNA isolated from UV-irradiated Chinese hamster ovary cells was reported (Mitchell et al., 1986). Our experiments showed that nucleotide excision repair enzyme might induce such of DNA modification in lymphocyte nuclei that increased specific antibody binding to DNA fragments with lesions. We suggest that enzymatic formation of open structures in DNA predominated qualitatively over dual-incision and excision of these fragments, and resulted in the enhanced exposure of the pyrimidine dimers in nuclei to specific antibodies. The results evidence that nucleotid excision repair in unstimualted human lymphocytes being deficient in dual incision and removal of UV-induced DNA lesions appear to be capable of performing chromatin relaxation and pre-incision uncoiling of DNA fragments with lesions.

  5. Ultraviolet light-induced cyclobutane pyrimidine dimers in rabbit eyes.

    Science.gov (United States)

    Mallet, Justin D; Rochette, Patrick J

    2011-01-01

    Sunlight exposure of the eye leads to pathologies including photokeratitis, cortical cataracts, pterygium, actinic conjunctivitis and age-related macular degeneration. It is well established that exposure to ultraviolet (UV) radiations leads to DNA damage, mainly cyclobutane pyrimidine dimers (CPDs). CPD formation is the principal factor involved in skin cancer. However, the exact mechanism by which sunlight induces ocular pathologies is not well understood. To shed light on this issue, we quantified the CPD formation onto DNA of rabbit ocular cells following UVB exposure. We found that CPDs were induced only in the structures of the ocular anterior chamber (cornea, iris and lens) and were more concentrated in the corneal epithelium. Residual UVB that pass through the cornea are completely absorbed by the anterior layers of the iris. CPDs were also detected in the central portion of the lens that is not protected by the iris (pupil). By determining the UV-induced DNA damage formation in eyes, we showed that anterior ocular structures are a reliable physical barrier that protects the subjacent structures from the toxic effects of UV. Although the corneal epithelium is the structure where most of the CPDs were detected, no cancer is related to solar exposure.

  6. Octyl Methoxycinnamate Modulates Gene Expression and Prevents Cyclobutane Pyrimidine Dimer Formation but not Oxidative DNA Damage in UV-Exposed Human Cell Lines

    Science.gov (United States)

    Duale, Nur; Olsen, Ann-Karin; Christensen, Terje; Butt, Shamas T.; Brunborg, Gunnar

    2010-01-01

    Octyl methoxycinnamate (OMC) is one of the most widely used sunscreen ingredients. To analyze biological effects of OMC, an in vitro approach was used implying ultraviolet (UV) exposure of two human cell lines, a primary skin fibroblast (GM00498) and a breast cancer (MCF-7) cell lines. End points include cell viability assessment, assay of cyclobutane pyrimidine dimers (CPDs) and oxidated DNA lesions using alkaline elution and lesion-specific enzymes, and gene expression analysis of a panel of 17 DNA damage–responsive genes. We observed that OMC provided protection against CPDs, and the degree of protection correlated with the OMC-mediated reduction in UV dose. No such protection was found with respect to oxidative DNA lesions. Upon UV exposure in the presence of OMC, the gene expression studies showed significant differential changes in some of the genes studied and the expression of p53 protein was also changed. For some genes, the change in expression seemed to be delayed in time by OMC. The experimental approach applied in this study, using a panel of 17 genes in an in vitro cellular system together with genotoxicity assays, may be useful in the initial screening of active ingredients in sunscreens. PMID:20071424

  7. UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?

    Science.gov (United States)

    Mouret, Stéphane; Philippe, Coralie; Gracia-Chantegrel, Jocelyne; Banyasz, Akos; Karpati, Szilvia; Markovitsi, Dimitra; Douki, Thierry

    2010-04-07

    The carcinogenic action of UVA radiation is commonly attributed to DNA oxidation mediated by endogenous photosensitisers. Yet, it was recently shown that cyclobutane pyrimidine dimers (CPD), well known for their involvement in UVB genotoxicity, are produced in larger yield than oxidative lesions in UVA-irradiated cells and skin. In the present work, we gathered mechanistic information on this photoreaction by comparing formation of all possible bipyrimidine photoproducts upon UVA irradiation of cells, purified genomic DNA and dA(20):dT(20) oligonucleotide duplex. We observed that the distribution of photoproducts, characterized by the sole formation of CPD and the absence of (6-4) photoproducts was similar in the three types of samples. The CPD involving two thymines represented 90% of the amount of photoproducts. Moreover, the yields of formation of the DNA lesions were similar in cells and isolated DNA. In addition, the effect of the wavelength of the incident photons was found to be the same in isolated DNA and cells. This set of data shows that UVA-induced cyclobutane pyrimidine dimers are formed via a direct photochemical mechanism, without mediation of a cellular photosensitiser. This is possible because the double-stranded structure increases the capacity of DNA bases to absorb UVA photons, as evidenced in the case of the oligomer dA(20):dT(20). These results emphasize the need to consider UVA in the carcinogenic effects of sunlight. An efficient photoprotection is needed that can only be complete by completely blocking incident photons, rather than by systemic approaches such as antioxidant supplementation.

  8. Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer.

    Science.gov (United States)

    Horikoshi, Naoki; Tachiwana, Hiroaki; Kagawa, Wataru; Osakabe, Akihisa; Matsumoto, Syota; Iwai, Shigenori; Sugasawa, Kaoru; Kurumizaka, Hitoshi

    2016-02-26

    The cyclobutane pyrimidine dimer (CPD) is induced in genomic DNA by ultraviolet (UV) light. In mammals, this photolesion is primarily induced within nucleosomal DNA, and repaired exclusively by the nucleotide excision repair (NER) pathway. However, the mechanism by which the CPD is accommodated within the nucleosome has remained unknown. We now report the crystal structure of a nucleosome containing CPDs. In the nucleosome, the CPD induces only limited local backbone distortion, and the affected bases are accommodated within the duplex. Interestingly, one of the affected thymine bases is located within 3.0 Å from the undamaged complementary adenine base, suggesting the formation of complementary hydrogen bonds in the nucleosome. We also found that UV-DDB, which binds the CPD at the initial stage of the NER pathway, also efficiently binds to the nucleosomal CPD. These results provide important structural and biochemical information for understanding how the CPD is accommodated and recognized in chromatin.

  9. Photoreactivation of pyrimidine dimers in DNA from thyroid cells of the teleost, Poecilia formosa

    Energy Technology Data Exchange (ETDEWEB)

    Achey, P.M.; Woodhead, A.D.; Setlow, R.B.

    1979-01-01

    We have developed and used a simple technique to estimate the quantity of pyrimidine dimers in unlabeled cellular DNA. DNA is extracted from cells, treated with an endonuclease specific for dimers, and its molecular weight estimated by its electrophoretic mobility on alkaline agarose slab gels. The technique is used to show that cells from thyroid tissue of the fish Poecilia formosa have photoreactivating activity towards dimmers in the cellular DNA.

  10. Removal of pyrimidine dimers in UV-irradiated spores of Dictyostelium discoideum during germination

    Energy Technology Data Exchange (ETDEWEB)

    Okaichi, K.; Tano, K.; Ohnishi, T.; Nozu, K.

    1985-06-01

    The spores of Dictyostelium discoideum TW-8 (radC) are about twice as sensitive to UV than the parental strain NC-4 spores at a 10% survival level. Ultraviolet irradiation apparently suppressed the emergence of amoebae from swollen TW-8 spores as compared with NC-4 spores, though the conversion of spores into swollen spores was not affected by UV irradiation in either strain. About 85% removal of pyrimidine dimers was detected in UV-irradiated NC-4 spores at 200 J/m/sup 2/ during spore germination for 9 h, but no removal of pyrimidine dimers was detected in TW-8 spores under the same conditions. The removal of pyrimidine dimers from the NC-4 spores began at around 2 h germination when the spores have become swollen. The number of enzyme-sensitive sites (ESS) detected by Micrococcus luteus endonuclease in the DNA of UV-irradiated NC-4 spores also began to decrease at about 2 h into germination. The decrease in ESS, however, was hardly detectable in UV-irradiated TW-8 spores at any step during germination. Cycloheximide inhibited both decrease in the number of pyrimidine dimers, and decrease in the number of ESS of UV-irradiated NC-4 spores. It is suggested that UV-specific endonuclease is newly synthesized in swollen spores of NC-4. (author).

  11. Detection of UV-induced cyclobutane pyrimidine dimers by near-infrared spectroscopy and aquaphotomics.

    Science.gov (United States)

    Goto, Noriko; Bazar, Gyorgy; Kovacs, Zoltan; Kunisada, Makoto; Morita, Hiroyuki; Kizaki, Seiichiro; Sugiyama, Hiroshi; Tsenkova, Roumiana; Nishigori, Chikako

    2015-07-02

    Ultraviolet (UV) radiation causes cellular DNA damage, among which cyclobutane pyrimidine dimers (CPDs) are responsible for a variety of genetic mutations. Although several approaches have been developed for detection of CPDs, conventional methods require time-consuming steps. Aquaphotomics, a new approach based on near-infrared spectroscopy (NIRS) and multivariate analysis that determines interactions between water and other components of the solution, has become an effective method for qualitative and quantitative parameters measurement in the solutions. NIR spectral patterns of UVC-irradiated and nonirradiated DNA solutions were evaluated using aquaphotomics for detection of UV-induced CPDs. Groups of UV-irradiated and nonirradiated DNA samples were classified (87.5% accuracy) by soft independent modeling of class analogy (SIMCA). A precise regression model calculated from NIR water spectral patterns based on UVC doses (r Val = 0.9457) and the concentration of cis-syn cyclobutane thymine dimers (cis-syn TTs; r Val = 0.9993) was developed using partial least squares regression (PLSR), while taking advantage of water spectral patterns, particularly around 1400-1500 nm. Our results suggested that, in contrast to DNA, the formation of cis-syn TTs increased the strongly hydrogen bonded water. Additionally, NIRS could qualitatively and quantitatively detect cis-syn TTs in isolated DNA aqueous solutions upon UVC exposure.

  12. Excision of pyrimidine dimers from nuclear deoxyribonucleic acid in ultraviolet-irradiated Dictyostelium discoideum

    Energy Technology Data Exchange (ETDEWEB)

    Clark, J.M.; Deering, R.A.

    1987-02-01

    A sensitive endonuclease assay was used to study the fate of pyrimidine dimers introduced by ultraviolet irradiation into the nuclear deoxyribonucleic acid of the cellular slime mold Dictyostellium discoideum. Analysis of the frequency of T4 endonuclease V-induced single-strand breaks by alkaline sucrose gradient sedimentation showed that strain NC4 (rad/sup +/) removed >98% of the dimers induced by irradiation at 40 J/m/sup 2/ (254 nm) within 215 min after irradiation. HPS104 (radC44), a mutant sensitive to ultraviolet irradiation, removed 91% under these conditions, although at a significantly slower rate than NC4: only 8% were removed during the 10- to 15- min period immediately after irradiation, whereas NC4 excised 64% during this interval. HPS104 thus appears to be deficient in the activity(ies) responsible for rapidly incising ultraviolet-irradiated nuclear deoxyribonucleic acid at the sites of pyrimidine dimers.

  13. Wavelength-dependent ultraviolet induction of cyclobutane pyrimidine dimers in the human cornea.

    Science.gov (United States)

    Mallet, Justin D; Rochette, Patrick J

    2013-08-01

    Exposition to ultraviolet (UV) light is involved in the initiation and the progression of skin cancer. The genotoxicity of UV light is mainly attributed to the induction of cyclobutane pyrimidine dimers (CPDs), the most abundant DNA damage generated by all UV types (UVA, B and C). The human cornea is also exposed to the harmful UV radiations, but no UV-related neoplasm has been reported in this ocular structure. The probability that a specific DNA damage leads to a mutation and eventually to cellular transformation is influenced by its formation frequency. To shed light on the genotoxic effect of sunlight in the human eye, we have analyzed CPD induction in the cornea and the iris following irradiation of ex vivo human eyes with UVA, B or C. The extent of CPD induction was used to establish the penetrance of the different UV types in the human cornea. We show that UVB- and UVC-induced CPDs are concentrated in the corneal epithelium and do not penetrate deeply beyond this corneal layer. On the other hand, UVA wavelengths penetrate deeper and induce CPDs in the entire cornea and in the first layers of the iris. Taken together, our results are undoubtedly an important step towards better understanding the consequences of UV exposure to the human eye.

  14. Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yarosh, Daniel B

    2002-11-30

    The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.

  15. Formation of Cystine Slipknots in Dimeric Proteins

    OpenAIRE

    Mateusz Sikora; Marek Cieplak

    2013-01-01

    We consider mechanical stability of dimeric and monomeric proteins with the cystine knot motif. A structure based dynamical model is used to demonstrate that all dimeric and some monomeric proteins of this kind should have considerable resistance to stretching that is significantly larger than that of titin. The mechanisms of the large mechanostability are elucidated. In most cases, it originates from the induced formation of one or two cystine slipknots. Since there are four termini in a dim...

  16. Rapid deamination of cyclobutane pyrimidine dimer photoproducts at TCG sites in a translationally and rotationally positioned nucleosome in vivo.

    Science.gov (United States)

    Cannistraro, Vincent J; Pondugula, Santhi; Song, Qian; Taylor, John-Stephen

    2015-10-30

    Sunlight-induced C to T mutation hot spots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. The C and 5-methyl-C in CPDs are not stable and deaminate to U and T, respectively, which leads to the insertion of A by the DNA damage bypass polymerase η, thereby defining a probable mechanism for the origin of UV-induced C to T mutations. Deamination rates for T(m)CG CPDs have been found to vary 12-fold with rotational position in a nucleosome in vitro. To determine the influence of nucleosome structure on deamination rates in vivo, we determined the deamination rates of CPDs at TCG sites in a stably positioned nucleosome within the FOS promoter in HeLa cells. A procedure for in vivo hydroxyl radical footprinting with Fe-EDTA was developed, and, together with results from a cytosine methylation protection assay, we determined the translational and rotational positions of the TCG sites. Consistent with the in vitro observations, deamination was slower for one CPD located at an intermediate rotational position compared with two other sites located at outside positions, and all were much faster than for CPDs at non-TCG sites. Photoproduct formation was also highly suppressed at one site, possibly due to its interaction with a histone tail. Thus, it was shown that CPDs of TCG sites deaminate the fastest in vivo and that nucleosomes can modulate both their formation and deamination, which could contribute to the UV mutation hot spots and cold spots.

  17. Formation of cystine slipknots in dimeric proteins.

    Directory of Open Access Journals (Sweden)

    Mateusz Sikora

    Full Text Available We consider mechanical stability of dimeric and monomeric proteins with the cystine knot motif. A structure based dynamical model is used to demonstrate that all dimeric and some monomeric proteins of this kind should have considerable resistance to stretching that is significantly larger than that of titin. The mechanisms of the large mechanostability are elucidated. In most cases, it originates from the induced formation of one or two cystine slipknots. Since there are four termini in a dimer, there are several ways of selecting two of them to pull by. We show that in the cystine knot systems, there is strong anisotropy in mechanostability and force patterns related to the selection. We show that the thermodynamic stability of the dimers is enhanced compared to the constituting monomers whereas machanostability is either lower or higher.

  18. Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: Remarkable UVB resistance and efficient DNA damage repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chongjie [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Ma, Li [Key Laboratory of Biofuels, and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101 (China); Mou, Shanli [Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao (China); Wang, Yibin, E-mail: wangyibin@fio.org.cn [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Zheng, Zhou; Liu, Fangming; Qi, Xiaoqing; An, Meiling; Chen, Hao [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Miao, Jinlai, E-mail: miaojinlai@163.com [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); State Key Laboratory of Biological Fermentation Engineering of Beer (In Preparation), Qingdao (China)

    2015-03-15

    Highlights: • Chlamydomonas sp. ICE-L photolyase gene PHR2 is first cloned and expressed in E. coli. • PHR2 complemented E. coli could efficiently survival from UV radiation. • Expressed PHR2 photolyase has distinct photo-reactivation activity in vitro. - Abstract: Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6 h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100 μw/cm{sup 2} UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field.

  19. Light-induced activation of class II cyclobutane pyrimidine dimer photolyases.

    Science.gov (United States)

    Okafuji, Asako; Biskup, Till; Hitomi, Kenichi; Getzoff, Elizabeth D; Kaiser, Gebhard; Batschauer, Alfred; Bacher, Adelbert; Hidema, Jun; Teranishi, Mika; Yamamoto, Kazuo; Schleicher, Erik; Weber, Stefan

    2010-05-04

    Light-induced activation of class II cyclobutane pyrimidine dimer (CPD) photolyases of Arabidopsis thaliana and Oryza sativa has been examined by UV/Vis and pulsed Davies-type electron-nuclear double resonance (ENDOR) spectroscopy, and the results compared with structure-known class I enzymes, CPD photolyase and (6-4) photolyase. By ENDOR spectroscopy, the local environment of the flavin adenine dinucleotide (FAD) cofactor is probed by virtue of proton hyperfine couplings that report on the electron-spin density at the positions of magnetic nuclei. Despite the amino-acid sequence dissimilarity as compared to class I enzymes, the results indicate similar binding motifs for FAD in the class II photolyases. Furthermore, the photoreduction kinetics starting from the FAD cofactor in the fully oxidized redox state, FAD(ox), have been probed by UV/Vis spectroscopy. In Escherichia coli (class I) CPD photolyase, light-induced generation of FADH from FAD(ox), and subsequently FADH(-) from FADH, proceeds in a step-wise fashion via a chain of tryptophan residues. These tryptophans are well conserved among the sequences and within all known structures of class I photolyases, but completely lacking from the equivalent positions of class II photolyase sequences. Nevertheless, class II photolyases show photoreduction kinetics similar to those of the class I enzymes. We propose that a different, but also effective, electron-transfer cascade is conserved among the class II photolyases. The existence of such electron transfer pathways is supported by the observation that the catalytically active fully reduced flavin state obtained by photoreduction is maintained even under oxidative conditions in all three classes of enzymes studied in this contribution.

  20. Kinetics and mechanism of electron-induced splitting of a cyclobutane pyrimidine dimer with or without an electron acceptor

    Institute of Scientific and Technical Information of China (English)

    YAN; Liqin(晏利琴); SONG; Qinhua(宋钦华); HEI; Xiaoming(黑晓明); WANG; Wenfeng(王文锋); GUO; Qingxiang(郭庆祥)

    2003-01-01

    Utilizing a pulse radiolysis equipment with time-resolved optical detector, kinetic processes of electron-induced splitting of cis-syn 1,3-dimethyluracil cyclobutane dimer (DMUD) in aqueous solution were investigated in the presence or absence of riboflavin (RF) or flavin adenine dinucleotide (FAD). It has been observed that the cyclobutane pyrimidine dimer reacting with hydrated electron splits spontaneously to give a monomer and a monomer radical anion, and the anion transfers one electron to RF or FAD. From the buildup kinetics of radical species, the rate constants of electron transfer from the monomer radical anion to RF and FAD have been determined. On the basis of comparison of the interactions between DMUD and hydrated electron in the presence and absence of RF or FAD, a chain reaction process in the absence of RF or FAD has been demonstrated.

  1. Fibrillar dimer formation of islet amyloid polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Chi-cheng [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); de Pablo, Juan J. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-05-08

    Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  2. Nuclear dynamics investigation of the initial electron transfer in the cyclobutane pyrimidine dimer lesion repair process by photolyases

    CERN Document Server

    Joubert-Doriol, Loic; Olivucci, Massimo; Izmaylov, Artur F

    2016-01-01

    Photolyases are proteins capable of harvesting the sunlight to repair DNA damages caused by UV light. In this work we focus on the first step in the repair process of the cyclobutane pyrimidine dimer photoproduct (CPD) lesion, which is an electron transfer (ET) from a flavine cofactor to CPD, and study the role of various nuclear degrees of freedom (DOF) in this step. The ET step has been experimentally studied using transient spectroscopy and the corresponding data provide excellent basis for testing the quality of quantum dynamical models. Based on previous theoretical studies of electronic structure and conformations of the protein active site, we present a procedure to build a diabatic Hamiltonian for simulating the ET reaction in a molecular complex mimicking the enzyme's active site. We generate a reduced nuclear dimensional model that provides a first non-empirical quantum dynamical description of the structural features influencing the ET rate. By varying the nuclear DOF parametrization in the model t...

  3. Potential formation of three pyrimidine bases in interstellar regions

    CERN Document Server

    Majumdar, Liton; Das, Ankan; Chakrabarti, Sandip K

    2015-01-01

    Work on the chemical evolution of pre-biotic molecules remains incomplete since the major obstacle is the lack of adequate knowledge of rate coefficients of various reactions which take place in interstellar conditions. In this work, we study the possibility of forming three pyrimidine bases, namely, cytosine, uracil and thymine in interstellar regions. Our study reveals that the synthesis of uracil from cytosine and water is quite impossible under interstellar circumstances. For the synthesis of thymine, reaction between uracil and :CH2 is investigated. Since no other relevant pathways for the formation of uracil and thymine were available in the literature, we consider a large gas-grain chemical network to study the chemical evolution of cytosine in gas and ice phases. Our modeling result shows that cytosine would be produced in cold, dense interstellar conditions. However, presence of cytosine is yet to be established. We propose that a new molecule, namely, C4N3OH5 could be observable in the interstellar ...

  4. Site-specific analysis of UV-induced cyclobutane pyrimidine dimers in nucleotide excision repair-proficient and -deficient hamster cells: Lack of correlation with mutational spectra

    Energy Technology Data Exchange (ETDEWEB)

    Vreeswijk, Maaike P.G., E-mail: vreeswijk@lumc.nl [Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, P.O. Box 9600, Postzone S4-P, 2300 RC Leiden (Netherlands); Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Building 2, Postzone S-04, P.O. Box 9600, 2300 RC Leiden (Netherlands); Meijers, Caro M.; Giphart-Gassler, Micheline; Vrieling, Harry; Zeeland, Albert A. van; Mullenders, Leon H.F.; Loenen, Wil A.M. [Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, P.O. Box 9600, Postzone S4-P, 2300 RC Leiden (Netherlands)

    2009-04-26

    Irradiation of cells with UVC light induces two types of mutagenic DNA photoproducts, i.e. cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). To investigate the relationship between the frequency of UV-induced photolesions at specific sites and their ability to induce mutations, we quantified CPD formation at the nucleotide level along exons 3 and 8 of the hprt gene using ligation-mediated PCR, and determined the mutational spectrum of 132 UV-induced hprt mutants in the AA8 hamster cell line and of 165 mutants in its nucleotide excision repair-defective derivative UV5. In AA8 cells, transversions predominated with a strong strand bias towards thymine-containing photolesions in the non-transcribed strand. As hamster AA8 cells are proficient in global genome repair of 6-4PP but selectively repair CPD from the transcribed strand of active genes, most mutations probably resulted from erroneous bypass of CPD in the non-transcribed strand. However, the relative incidence of CPD and the positions where mutations most frequently arose do not correlate. In fact some major damage sites hardly gave rise to the formation of mutations. In the repair-defective UV5 cells, mutations were almost exclusively C > T transitions caused by photoproducts at PyC sites in the transcribed strand. Even though CPD were formed at high frequencies at some TT sites in UV5, these photoproducts did not contribute to mutation induction at all. We conclude that, even in the absence of repair, large variations in the level of induction of CPD at different sites throughout the two exons do not correspond to frequencies of mutation induction.

  5. Site-specific analysis of UV-induced cyclobutane pyrimidine dimers in nucleotide excision repair-proficient and -deficient hamster cells: Lack of correlation with mutational spectra.

    Science.gov (United States)

    Vreeswijk, Maaike P G; Meijers, Caro M; Giphart-Gassler, Micheline; Vrieling, Harry; van Zeeland, Albert A; Mullenders, Leon H F; Loenen, Wil A M

    2009-04-26

    Irradiation of cells with UVC light induces two types of mutagenic DNA photoproducts, i.e. cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4 PP). To investigate the relationship between the frequency of UV-induced photolesions at specific sites and their ability to induce mutations, we quantified CPD formation at the nucleotide level along exons 3 and 8 of the hprt gene using ligation-mediated PCR, and determined the mutational spectrum of 132 UV-induced hprt mutants in the AA8 hamster cell line and of 165 mutants in its nucleotide excision repair-defective derivative UV5. In AA8 cells, transversions predominated with a strong strand bias towards thymine-containing photolesions in the non-transcribed strand. As hamster AA8 cells are proficient in global genome repair of 6-4 PP but selectively repair CPD from the transcribed strand of active genes, most mutations probably resulted from erroneous bypass of CPD in the non-transcribed strand. However, the relative incidence of CPD and the positions where mutations most frequently arose do not correlate. In fact some major damage sites hardly gave rise to the formation of mutations. In the repair-defective UV5 cells, mutations were almost exclusively C>T transitions caused by photoproducts at PyC sites in the transcribed strand. Even though CPD were formed at high frequencies at some TT sites in UV5, these photoproducts did not contribute to mutation induction at all. We conclude that, even in the absence of repair, large variations in the level of induction of CPD at different sites throughout the two exons do not correspond to frequencies of mutation induction.

  6. In Vivo Spectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers.

    Science.gov (United States)

    Ikehata, Hironobu; Mori, Toshio; Yamamoto, Masayuki

    2015-11-01

    Although ultraviolet radiation (UVR) has a genotoxicity for inducing skin cancers, the skin may tolerate UVC component because the epidermal layer prevents this short wavelength range from passing through. Here, UVC genotoxicity for mouse skin was evaluated in terms of DNA damage formation and mutagenicity. UVC induced UVR photolesions and mutations remarkably in the epidermis but poorly in the dermis, confirming the barrier ability of the epidermis against shorter UVR wavelengths. Moreover, the epidermis itself responded to UVC mutagenicity with mutation induction suppression, which suppressed the mutant frequencies to a remarkably low, constant level regardless of UVC dose. The mutation spectrum observed in UVC-exposed epidermis showed a predominance of UV-signature mutation, which occurred frequently in 5'-TCG-3', 5'-TCA-3' and 5'-CCA-3' contexts. Especially, for the former two contexts, the mutations recurred at several sites with more remarkable recurrences at the 5'-TCG-3' sites. Comparison of the UVC mutation spectrum with those observed in longer UVR wavelength ranges led us to a mechanism that explains why the sequence context preference of UV-signature mutation changes according to the wavelength, which is based on the difference in the mCpG preference of cyclobutane pyrimidine dimer (CPD) formation among UVR ranges and the sequence context-dependent cytosine deamination propensity of CPD.

  7. Photochemistry of Pyrimidine in Astrophysical Ices: Formation of Nucleobases and Other Prebiotic Species

    Science.gov (United States)

    Nuevo, Michel; Sandford, Scott A.; Materese, Christopher K.; Milam, Stefanie N.

    2012-01-01

    Nucleobases are N-heterocycles that are the informational subunits of DNA and RNA. They are divided into two molecular groups: pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in meteorites, and their extraterrestrial origin confirmed by isotopic measurements. Although no N-heterocycles have ever been observed in the ISM, the positions of the 6.2- m interstellar emission features suggest a population of such molecules is likely to be present. However, laboratory experiments have shown that the ultraviolet (UV) irradiation of pyrimidine in ices of astrophysical relevance such as H2O, NH3, CH3OH, CH4, CO, or combinations of these at low temperature (less than or equal to 20 K) leads to the formation of several pyrimidine derivatives including the nucleobases uracil and cytosine, as well as precursors such as 4(3H)-pyrimidone and 4-aminopyrimidine. Quantum calculations on the formation of 4(3H)-pyrimidone and uracil from the irradiation of pyrimidine in pure H2O ices are in agreement with their experimental formation pathways.10 In those residues, other species of prebiotic interest such as urea as well as the amino acids glycine and alanine could also be identified. However, only very small amounts of pyrimidine derivatives containing CH3 groups could be detected, suggesting that the addition of methyl groups to pyrimidine is not an efficient process. For this reason, the nucleobase thymine was not observed in any of the samples. In this work, we study the formation of nucleobases and other photo-products of prebiotic interest from the UV irradiation of pyrimidine in ices containing H2O, NH3, CH3OH, and CO, mixed in astrophysical proportions.

  8. Chemical modification of the third strand: differential effects on purine and pyrimidine triple helix formation.

    Science.gov (United States)

    Mills, Martin; Arimondo, Paola B; Lacroix, Laurent; Garestier, Thérèse; Klump, Horst; Mergny, Jean-Louis

    2002-01-08

    DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of gene expression. Oligonucleotide analogues are routinely used with modifications in either the backbone or the bases to form more stable triple-helical structures or to prevent their degradation in cells. In this article, different chemical modifications are tested in a model system, which sets up a competition between the purine and pyrimidine motifs. For most modifications, the DeltaH degrees of purine triplex formation is close to zero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex is strongly favored at lower temperatures. The stabilization induced by modifications previously known to be favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GT motif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands compete for triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on the chemical nature of the triplex-forming strands and the stability of the corresponding triplexes.

  9. Molecular Dynamics Simulation of Amyloid Beta Dimer Formation

    CERN Document Server

    Urbanc, B; Ding, F; Sammond, D; Khare, S; Buldyrev, S V; Stanley, H E; Dokholyan, N V

    2004-01-01

    Recent experiments with amyloid-beta (Abeta) peptide suggest that formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depends on their structure, which is governed by assembly dynamics. Due to limitations of current experimental techniques, a detailed knowledge of oligomer structure at the atomic level is missing. We introduce a molecular dynamics approach to study Abeta dimer formation: (1) we use discrete molecular dynamics simulations of a coarse-grained model to identify a variety of dimer conformations, and (2) we employ all-atom molecular mechanics simulations to estimate the thermodynamic stability of all dimer conformations. Our simulations of a coarse-grained Abeta peptide model predicts ten different planar beta-strand dimer conformations. We then estimate the free energies of all dimer conformations in all-atom molecular mechanics simulations with explicit water. We compare the free energies of Abeta(1-42) and Abeta(1-40...

  10. Inducible removal of UV-induced pyrimidine dimers from transcriptionally active and inactive genes of Saccharomyces cerevisiae.

    Science.gov (United States)

    Waters, R; Zhang, R; Jones, N J

    1993-05-01

    The prior UV irradiation of alpha haploid Saccharomyces cerevisiae with a UV dose of 25 J/m2 substantially increases the repairability of damage subsequently induced by a UV dose of 70 J/m2 given 1 h after the first irradiation. This enhancement of repair is seen at both the MAT alpha and HML alpha loci, which are, respectively, transcriptionally active and inactive in alpha haploid cells. The presence in the medium of the protein synthesis inhibitor, cycloheximide in the period between the two irradiations eliminated this effect. Enhanced repair still occurred if cycloheximide was present only after the final UV irradiation. This indicated that the first result is not due to cycloheximide merely blocking the synthesis of repair enzymes associated with a hypothetical rapid turnover of such molecules. The enhanced repairability is not the result of changes in chromatin accessibility without protein synthesis, merely caused by the repair of the damage induced by the prior irradiation. The data clearly show that a UV-inducible removal of pyrimidine dimers has occurred which involves the synthesis of new proteins. The genes known to possess inducible promoters, and which are involved in excision are RAD2, RAD7, RAD16 and RAD23. Studies with the rad7 and rad16 mutants which are defective in the ability to repair HML alpha and proficient in the repair of MAT alpha showed that in rad7, preirradiation enhanced the repair at MAT alpha, whereas in rad16 this increased repair of MAT alpha was absent. The preirradiation did not modify the inability to repair HML alpha in either strain. Thus RAD16 has a role in this inducible repair.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The Roles of Several Residues of Escherichia coli DNA Photolyase in the Highly Efficient Photo-Repair of Cyclobutane Pyrimidine Dimers

    Directory of Open Access Journals (Sweden)

    Lei Xu

    2010-01-01

    Full Text Available Escherichia coli DNA photolyase is an enzyme that repairs the major kind of UV-induced lesions, cyclobutane pyrimidine dimer (CPD in DNA utilizing 350–450 nm light as energy source. The enzyme has very high photo-repair efficiency (the quantum yield of the reaction is ~0.85, which is significantly greater than many model compounds that mimic photolyase. This suggests that some residues of the protein play important roles in the photo-repair of CPD. In this paper, we have focused on several residues discussed their roles in catalysis by reviewing the existing literature and some hypotheses.

  12. Formation of Nucleobases from the UV Irradiation of Pyrimidine in Astrophysical Ice Analogs

    Science.gov (United States)

    Sandford, Scott A.; Nuevo, Michel; Materese, Christopher K.

    2014-01-01

    Nucleobases are the informational subunits of DNA and RNA. They consist of Nheterocycles that belong to either the pyrimidine-base group (uracil, cytosine, and thymine) or the purinebase group (adenine and guanine). Several nucleobases, mostly purine bases, have been detected in meteorites [1-3], with isotopic signatures consistent with an extraterrestrial origin [4]. Uracil is the only pyrimidine-base compound formally reported in meteorites [2], though the presence of cytosine cannot be ruled out [5,6]. However, the actual process by which the uracil was made and the reasons for the non-detection of thymine in meteorites have yet to be fully explained. Although no N-heterocycles have ever been observed in the ISM [7,8], the positions of the 6.2-µm interstellar emission features suggest a population of such molecules is likely to be present [9]. In this work we study the formation of pyrimidine-based molecules, including the three nucleobases uracil, cytosine, and thymine from the ultraviolet (UV) irradiation of pyrimidine in ices consisting of several combinations of H(sub2)O, NH(sub3), CH(sub3)OH, and CH(sub4) at low temperature, in order to simulate the astrophysical conditions under which prebiotic species may be formed in the interstellar medium, in the protosolar nebula, and on icy bodies of the Solar System.

  13. Self-assembling of cytosine nucleoside into triply-bound dimers in acid media. A comprehensive evaluation of proton-bound pyrimidine nucleosides by electrospray tandem mass spectrometry, X-rays diffractometry, and theoretical calculations.

    Science.gov (United States)

    Armentano, Donatella; De Munno, Giovanni; Di Donna, Leonardo; Sindona, Giovanni; Giorgi, Gianluca; Salvini, Laura; Napoli, Anna

    2004-02-01

    Electrospray tandem mass spectrometry (ESI-MS/MS) is used to evaluate the assembling of cytosine and thymine nucleosides in the gas phase, through the formation of hydrogen bonded supermolecules. Mixtures of cytidine analogues and homologues deliver in the gas phase proton-bound heterodimers stabilized by multiple interactions, as proven by the kinetics of their dissociation into the corresponding protonated monomers. Theoretical calculations, performed on initial structures of methylcytosine homodimers available in the literature, converged to a minimized structure whereby the two pyrimidine rings interact through the formation of three hydrogen bonds of similar energy. The crystallographic data here reported show the equivalency of the two interacting pyrimidines which is attributable to the presence of an inversion center. Thymine and uracil pyrimidyl nucleosides form, by ESI, gaseous proton-bound dimers. The kinetic of their dissociation into the related protonated monomers shows that the nucleobases are weekly interacting through a single hydrogen bond. The minimized structure of the protonated heterodimer formed by thymine and N-1-methylthymine confirmed the existence of mainly one hydrogen bond which links the two nucleobases through the O4 oxygens. No crystallographic data exists on thymine proton-bound species, nor have we been able to obtain these aggregates in the solid phase. The gaseous phase, under high vacuum conditions, seems therefore a suitable environment where vanishing structures produced by ESI can be studied with a good degree of approximation.

  14. The Photochemistry of Pyrimidine in Pure H2O Ice Subjected to Different Radiation Environments and the Formation of Uracil

    Science.gov (United States)

    Nuevo, M.; Chen, Y.-J.; Materese. C. K..; Hu, W.-J.; Qiu, J.-M.; Wu, S.-R.; Fung, H.-S.; Sandford, S. A.; Chu, C.-C.; Yih, T.-S.; Wu, R.; Ip, W.-H.

    2013-01-01

    Nucleobases are N-heterocycles which are the informational subunits of DNA and RNA. They include pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in several meteorites, although no Nheterocycles have been observed in space to data. Laboratory experiments showed that the ultraviolet (UV) irradiation of pyrimidine in pure H2O ice at low temperature (<=20 K) leads to the formation of pyrimidine derivatives including the nucleobase uracil and its precursor 4(3H)-pyrimidone. These results were confirmed by quantum chemical calculations. When pyrimidine is mixed with combinations of H2O, NH3, CH3OH, and CH4 ices under similar conditions, uracil and cytosine are formed. In the present work we study the formation of 4(3H)-pyrimidone and uracil from the irradiation of pyrimidine in H2O ice with high-energy UV photons (Lyman , He I, and He II lines) provided by a synchrotron source. The photo-destruction of pyrimidine in these H2O ices as well as the formation yields for 4(3H)-pyrimidone and uracil are compared with our previous results in order to study the photo-stability of pyrimidine and the production efficiency of uracil as a function of the photon energy.

  15. DLTS study of the oxygen dimer formation kinetics in silicon

    Science.gov (United States)

    Yarykin, Nikolai; Weber, Jörg

    2009-12-01

    The introduction rates of radiation defects, in particular the X- and M-centers for which the oxygen dimer is a precursor, are investigated as a function of duration of the pre-irradiation heat treatment at 480∘ C in Czochralski-grown silicon both of n- and p-types. The characteristic annealing time to grow the X-center concentration in the n-type crystal is found to be about 1 h in accordance with the model which implies no significant barrier for the dimer formation. The M-center concentration in the p-type crystal is found to be nearly independent of duration of the pre-irradiation annealing after a few minutes transient period. This behavior is ascribed to the stabilization of dimer concentration due to an effective dimer trapping in these samples.

  16. DLTS study of the oxygen dimer formation kinetics in silicon

    Energy Technology Data Exchange (ETDEWEB)

    Yarykin, Nikolai, E-mail: nay@iptm.r [Institute of Microelectronics Technology RAS, 142432 Chernogolovka, Moscow Region (Russian Federation); Weber, Joerg [Technische Universitaet Dresden, 01062 Dresden (Germany)

    2009-12-15

    The introduction rates of radiation defects, in particular the X- and M-centers for which the oxygen dimer is a precursor, are investigated as a function of duration of the pre-irradiation heat treatment at 480 deg. C in Czochralski-grown silicon both of n- and p-types. The characteristic annealing time to grow the X-center concentration in the n-type crystal is found to be about 1 h in accordance with the model which implies no significant barrier for the dimer formation. The M-center concentration in the p-type crystal is found to be nearly independent of duration of the pre-irradiation annealing after a few minutes transient period. This behavior is ascribed to the stabilization of dimer concentration due to an effective dimer trapping in these samples.

  17. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.

    Science.gov (United States)

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-10-03

    The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  18. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Du, Fengxia [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Zhang, Minjie [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Xiaohua; Yang, Caiyun [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Meng, Hao; Wang, Dong; Chang, Shuang [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xu, Ye [Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States); Price, Brendan, E-mail: Brendan_Price@dfci.harvard.edu [Department of Radiation Oncology, Division of Genomic Stability, Dana Farber Cancer Institute, Harvard Medical School, MA 02134 (United States); Sun, Yingli, E-mail: sunyl@big.ac.cn [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-10-03

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  19. Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

    Energy Technology Data Exchange (ETDEWEB)

    Komura, Jun-ichiro, E-mail: junkom@med.tohoku.ac.jp [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Ikehata, Hironobu [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Mori, Toshio [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan); Ono, Tetsuya [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)

    2012-03-10

    During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: Black-Right-Pointing-Pointer Global genome repair of (6-4) photoproducts is fully active in mitotic cells. Black-Right-Pointing-Pointer DNA in condensed mitotic chromatin does not seem inaccessible or inert. Black-Right-Pointing-Pointer Mitotic transcriptional repression may impair transcription-coupled repair.

  20. Resistance of the genome of Escherichia coli and Listeria monocytogenes to irradiation evaluated by the induction of cyclobutane pyrimidine dimers and 6-4 photoproducts using gamma and UV-C radiations

    Science.gov (United States)

    Beauchamp, S.; Lacroix, M.

    2012-08-01

    The effect of gamma and UV-C irradiation on the production of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4 PPs) in DNA was investigated to compare the natural resistance of the genome of a Gram-positive bacterium and a Gram-negative bacterium against irradiation. Solution of pure DNA and bacterial strains Listeria monocytogenes and Escherichia coli were irradiated using gamma and UV-C rays. Extracted DNA from bacteria and pure DNA samples were then analysed by ELISA using anti-CPDs and anti-6-4 PPs monoclonal antibodies. The results show that gamma rays, as well as UV-C rays, induce the formation of CPDs and 6-4 PPs in DNA. During UV-C irradiation, the three samples showed a difference in their sensitivity against formation of CPDs (P≤0.05). Pure DNA was the most sensitive while the genome of L. monocytogenes was the most resistant. Also during UV-C irradiation, the genome of L. monocytogenes was the only one to show a significant resistance against formation of 6-4 PPs (P≤0.05). During gamma irradiation, for both types of lesion, pure DNA and the genome of E. coli did not show significant difference in their sensitivity (P>0.05) while the genome of L. monocytogenes showed a resistance against formation of CPDs and 6-4 PPs.

  1. GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Paul M.; Viti, Serena [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom); Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J., E-mail: p.woods@qub.ac.uk [Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom)

    2013-11-10

    Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints.

  2. Glycolaldehyde Formation via the Dimerization of the Formyl Radical

    Science.gov (United States)

    Woods, Paul M.; Slater, Ben; Raza, Zamaan; Viti, Serena; Brown, Wendy A.; Burke, Daren J.

    2013-11-01

    Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints.

  3. Excited State Pathways Leading to Formation of Adenine Dimers.

    Science.gov (United States)

    Banyasz, Akos; Martinez-Fernandez, Lara; Ketola, Tiia-Maaria; Muñoz-Losa, Aurora; Esposito, Luciana; Markovitsi, Dimitra; Improta, Roberto

    2016-06-02

    The reaction intermediate in the path leading to UV-induced formation of adenine dimers A═A and AA* is identified for the first time quantum mechanically, using PCM/TD-DFT calculations on (dA)2 (dA: 2'deoxyadenosine). In parallel, its fingerprint is detected in the absorption spectra recorded on the millisecond time-scale for the single strand (dA)20 (dA: 2'deoxyadenosine).

  4. Formation of Nucleobases from the UV Photo-Irradiation of Pyrimidine in Astrophysical Ice Analogs

    Science.gov (United States)

    Milam, S. N.; Nuevo, M.; Sandford, S. A.; Elsila, J. E.; Dworkin, J. P.

    2010-01-01

    Astrochemistry laboratory simulations have shown that complex organic molecules including compounds of astrobiological interest can be formed under interstellarl/circumstellar conditions from the vacuum UV irradiation of astrophysical ice analogs containing H2O, CO, CO2, CH3OH, NH13, etc. Of all prebiotic compounds, the formation of amino acids under such experimental conditions has been the most extensively studied. Although the presence of amino acids in the interstellar medium (ISM) has yet to be confirmed, they have been detected in meteorites, indicating that biomolecules and/or their precursors can be formed under extraterrestrial, abiotic conditions. Nucleobases, the building blocks of DNA and RNA, as well as other 1V-heterocycles, have also been detected in meteorites, but like amino acids, they have yet to be observed in the ISM. In this work, we present an experimental study of the formation of pyrimidine-based compounds from the UV photo-irradiation of pyrimidine in ice mixtures containing H2O, NH3, and/or CH3OH at low temperature and pressure.

  5. Anti-parallel dimer and tetramer formation of propylene carbonate

    Directory of Open Access Journals (Sweden)

    Ayana Tagawa

    2017-09-01

    Full Text Available Raman scattering and infrared (IR absorption spectra of enantiopure (R-propylene carbonate ((RPC and racemic propylene carbonate (PC were recorded at room temperature, 25 °C, in benzene (Bz solution and in the pure liquid state to investigate the presence of dimers and other higher order intermolecular associations. (RPC and PC both demonstrated a strong C=O stretching vibrational band. The band exhibited changes in its shape and resonance wavenumber highly dependent on the concentrations of PCs, whereas a difference between the chirality of (RPC and PC had little influence. In an extremely dilute condition, doubly split bands were observed at 1807 and 1820 cm-1 in both Raman and IR spectra, which are assigned to the characteristic bands of isolated monomeric PCs. An additional band appeared at 1795 cm-1 in a dilute to concentrated regime, and its magnitude strengthened with increasing concentrations accompanied with slight increasing in the magnitude of 1807 cm-1 band in Raman spectra, while an increase in the magnitude of 1807 cm-1 band was clearly greater than that of 1795 cm-1 band in IR spectra. The spectrum changes at 1795 and 1807 cm-1 were attributed to characteristics of anti-parallel dimer formation of PCs caused by strong dipole-dipole interactions between C=O groups. Moreover, another additional signal was clearly observed at 1780-1790 cm-1 in a concentrated regime, and became the primary signal in the pure liquid state with slight increasing in the intensity of 1795 cm-1 band in Raman spectra. On the other hand, in IR spectra the observed increasing of 1780-1790 cm-1 band was much less than that of 1795 cm-1 band. These newly found spectrum changes in the concentrated regime are attributed to the formation of anti-parallel tetramers of PCs based on the characteristics of band selection rule found in Raman and IR spectra. Equilibrium constants for the anti-parallel dimer (KD and tetramer formation (KT of PCs in Bz solution and in

  6. Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation

    Science.gov (United States)

    Liao, Chenyi; Zhang, Zhi; Kale, Justin; Andrews, David W.; Lin, Jialing; Li, Jianing

    2016-07-01

    Helix α9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the α9 dimer in a MOM model — using computer simulations supplemented with site-specific mutagenesis and crosslinking of the α9 helices. Our data not only confirmed the critical membrane environment for the α9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The corroborating evidence from simulations and experiments suggests that, helix α9 assists Bax activation via the dimer heterogeneity and interactions with specific MOM lipids, which eventually facilitate proteolipidic pore formation in apoptosis regulation.

  7. Probing mechanism of α-formylketene dithioacetal towards the facile formation of functionalized pyrimidines: A structural approach

    Science.gov (United States)

    Joy, Monu; Adeniyi, Adebayo A.; Mathews, Annie; Mathew, Bijo; Prasanth, S.; Soliman, Mohmoud E. S.; Malayan, Jalaja J.; Anabha, E. R.

    2017-01-01

    α-Formylketene dithioacetal is an active precursor for the synthesis of a variety of organic compounds including pyrimidines and its functionalized materials. The present study deals with the structural versatility of a solid representative compound from the family of α-formylketene dithioacetal to the formation of functionalized pyrimidines derivatives through experimental as well as theoretical methods. 2-(3,4-dimethoxybenzoyl)-3,3-bis(methylsulfanyl)prop-2-enal, the representative compound was synthesized with a reported protocol and characterized through spectral methods. The complete three dimensional solid state structural studies were carried out utilizing single crystal X-ray crystallographic technique along with theoretical methods like classical and accelerated molecular dynamics simulation. Various quantum chemical parameters were also discussed to reveals the complete molecular geometry and reactivity of designated compound.

  8. Dimer and String Formation during Low Temperature Silicon Deposition on Si(100)

    DEFF Research Database (Denmark)

    Smith, A. P.; Jonsson, Hannes

    1996-01-01

    We present theoretical results based on density functional theory and kinetic Monte Carlo simulations of silicon deposition and address observations made in recently reported low temperature scanning tunneling microscopy studies. A mechanism is presented which explains dimer formation on top...... of the substrate's dimer rows at 160 K and up to room temperature, while between-row dimers and longer strings of adatoms (''diluted dimer rows'') form at higher temperature. A crossover occurs at around room temperature between two different mechanisms for adatom diffusion in our model....

  9. Dimeric interactions and complex formation using direct coevolutionary couplings.

    Science.gov (United States)

    dos Santos, Ricardo N; Morcos, Faruck; Jana, Biman; Andricopulo, Adriano D; Onuchic, José N

    2015-09-04

    We develop a procedure to characterize the association of protein structures into homodimers using coevolutionary couplings extracted from Direct Coupling Analysis (DCA) in combination with Structure Based Models (SBM). Identification of dimerization contacts using DCA is more challenging than intradomain contacts since direct couplings are mixed with monomeric contacts. Therefore a systematic way to extract dimerization signals has been elusive. We provide evidence that the prediction of homodimeric complexes is possible with high accuracy for all the cases we studied which have rich sequence information. For the most accurate conformations of the structurally diverse dimeric complexes studied the mean and interfacial RMSDs are 1.95Å and 1.44Å, respectively. This methodology is also able to identify distinct dimerization conformations as for the case of the family of response regulators, which dimerize upon activation. The identification of dimeric complexes can provide interesting molecular insights in the construction of large oligomeric complexes and be useful in the study of aggregation related diseases like Alzheimer's or Parkinson's.

  10. The reaction of the acrylonitrile ion CH 2dbnd CH-C tbnd N rad + with HCN: Proton-transport catalysis vs formation of ionized pyrimidine

    Science.gov (United States)

    Ervasti, Henri K.; Jobst, Karl J.; Gerbaux, Pascal; Burgers, Peter C.; Ruttink, Paul J. A.; Terlouw, Johan K.

    2009-11-01

    The CBS-QB3 model chemistry predicts that the title ion-molecule reaction, of potential interest in astrochemistry, yields a stable head-to-tail dimer, [HC dbnd N-CH 2C(H)C tbnd N] rad + ( D1). Cyclization of D1 into ionized pyrimidine seems possible, but the initiating 1,2-H shift is close in energy to back-dissociation into CH 2dbnd C(H)CN rad + ( AN) + HCN. Less energy demanding is formation of the H-bridged isomers [CH 2dbnd C(CN)H--N tbnd CH] rad + and [HC tbnd N--HC(H) dbnd C(H)CN] rad +, whose HCN component may catalyze isomerization of AN into CH 2dbnd C dbnd C dbnd NH rad + ( AN1) and CH dbnd C(H)C dbnd NH rad + ( AN2) respectively. Tandem mass spectrometry based experiments using 15N/ 13C labelling show that cyclization of D1 does not occur and that AN1 is the predominant reaction product instead.

  11. Formation and occurrence of dimer esters of pinene oxidation products in atmospheric aerosols

    DEFF Research Database (Denmark)

    Kristensen, Kasper; Enggrob, Kirsten L.; King, S. M.

    2013-01-01

    The formation of carboxylic acids and dimer esters from alpha-pinene oxidation was investigated in a smog chamber and in ambient aerosol samples collected during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX). Chamber experiments of alpha-pinene ozonolysis in dry air...... and at low NOx concentrations demonstrated formation of two dimer esters, pinyl-diaterpenyl (MW 358) and pinonyl-pinyl dimer ester (MW 368), under both low- and high-temperature conditions. Concentration levels of the pinyl-diaterpenyl dimer ester were lower than the assumed first-generation oxidation...... products cis-pinic and terpenylic acids, but similar to the second-generation oxidation products 3-methyl-1,2,3-butane tricarboxylic acid (MBTCA) and diaterpenylic acid acetate (DTAA). Dimer esters were observed within the first 30 min, indicating rapid production simultaneous to their structural...

  12. Formation and diffusion of water dimers on rutile TiO2(110).

    Science.gov (United States)

    Matthiesen, J; Hansen, J O; Wendt, S; Lira, E; Schaub, R; Laegsgaard, E; Besenbacher, F; Hammer, B

    2009-06-05

    From an interplay of time-lapsed high resolution scanning tunneling microscopy and density functional theory calculations we reveal the formation and diffusion of water dimers on hydrated rutile TiO2(110)-(1x1) surfaces, i.e., surfaces containing OH_{br} groups. At temperatures between approximately 150 and approximately 210 K water monomers diffusing along the Ti troughs were found to form stable water dimers that diffuse faster than the water monomers. An H bond mediated rollover mechanism operating for the water dimers explains the experimental findings.

  13. Duplex and triplex formation of mixed pyrimidine oligonucleotides with stacking of phenyl-triazole moieties in the major groove

    DEFF Research Database (Denmark)

    Andersen, Nicolai Krog; Døssing, Holger Balslev; Jensen, Frank;

    2011-01-01

    5-(1-Phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine was synthesized from a modified CuAAC protocol and incorporated into mixed pyrimidine oligonucleotide sequences together with the corresponding 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine. With consecutive incorporations of the two modified...... nucleosides, improved duplex formation with a complementary RNA and improved triplex formation with a complementary DNA duplex were observed. The improvement is due to π-π stacking of the phenyl-triazole moieties in the major groove. The strongest stacking and most pronounced positive influence on thermal...... stability was found in between the uridine analogues or with the cytidine analogue placed in the 3' direction to the uridine analogue. Modeling indicated a different orientation of the phenyl-triazole moieties in the major groove to account for the difference between the two nucleotides. The modified...

  14. Dimerization interface of 3-hydroxyacyl-CoA dehydrogenase tunes the formation of its catalytic intermediate.

    Directory of Open Access Journals (Sweden)

    Yingzhi Xu

    Full Text Available 3-Hydroxyacyl-CoA dehydrogenase (HAD, EC 1.1.1.35 is a homodimeric enzyme localized in the mitochondrial matrix, which catalyzes the third step in fatty acid β-oxidation. The crystal structures of human HAD and subsequent complexes with cofactor/substrate enabled better understanding of HAD catalytic mechanism. However, numerous human diseases were found related to mutations at HAD dimerization interface that is away from the catalytic pocket. The role of HAD dimerization in its catalytic activity needs to be elucidated. Here, we solved the crystal structure of Caenorhabditis elegans HAD (cHAD that is highly conserved to human HAD. Even though the cHAD mutants (R204A, Y209A and R204A/Y209A with attenuated interactions on the dimerization interface still maintain a dimerization form, their enzymatic activities significantly decrease compared to that of the wild type. Such reduced activities are in consistency with the reduced ratios of the catalytic intermediate formation. Further molecular dynamics simulations results reveal that the alteration of the dimerization interface will increase the fluctuation of a distal region (a.a. 60-80 that plays an important role in the substrate binding. The increased fluctuation decreases the stability of the catalytic intermediate formation, and therefore the enzymatic activity is attenuated. Our study reveals the molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects.

  15. Synthesis, Dimeric Crystal Structure, and Biological Activities of N-(4-Methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl)-N-(2-trifluoromethyl-phenyl)-guanidine

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The title compound, N-(4-methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl)-N′-(2-trifluoromethyl-phenyl)-guanidine, was synthesized and its structure was confirmed by using IR, MS, 1H NMR, and elemental analysis. The single crystal structure of the title compound was determined by X-ray diffraction. The preliminary biological test showed that the synthesized compound has a weak herbicidal activity.

  16. A strategy for complex dimer formation when biomimicry fails: total synthesis of ten coccinellid alkaloids.

    Science.gov (United States)

    Sherwood, Trevor C; Trotta, Adam H; Snyder, Scott A

    2014-07-09

    Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature's presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strategy for dimer formation that obviates these difficulties, one which rapidly constructs the coccinellid dimers psylloborine A and isopsylloborine A through a terminating sequence of two reaction cascades that generate five bonds, five rings, and four stereocenters. In addition, a common synthetic intermediate is identified which allows for the rapid, asymmetric formal or complete total syntheses of eight monomeric members of the class.

  17. A balanced pyrimidine pool is required for optimal Chk1 activation to prevent ultrafine anaphase bridge formation.

    Science.gov (United States)

    Gemble, Simon; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Biard, Denis; Lambert, Sarah; Amor-Guéret, Mounira

    2016-08-15

    Cytidine deaminase (CDA) deficiency induces an excess of cellular dCTP, which reduces basal PARP-1 activity, thereby compromising complete DNA replication, leading to ultrafine anaphase bridge (UFB) formation. CDA dysfunction has pathological implications, notably in cancer and in Bloom syndrome. It remains unknown how reduced levels of PARP-1 activity and pyrimidine pool imbalance lead to the accumulation of unreplicated DNA during mitosis. We report that a decrease in PARP-1 activity in CDA-deficient cells impairs DNA-damage-induced Chk1 activation, and, thus, the downstream checkpoints. Chemical inhibition of the ATR-Chk1 pathway leads to UFB accumulation, and we found that this pathway was compromised in CDA-deficient cells. Our data demonstrate that ATR-Chk1 acts downstream from PARP-1, preventing the accumulation of unreplicated DNA in mitosis, and, thus, UFB formation. Finally, delaying entry into mitosis is sufficient to prevent UFB formation in both CDA-deficient and CDA-proficient cells, suggesting that both physiological and pathological UFBs are derived from unreplicated DNA. Our findings demonstrate an unsuspected requirement for a balanced nucleotide pool for optimal Chk1 activation both in unchallenged cells and in response to genotoxic stress.

  18. Influence of cyclic dimer formation on the phase behavior of carboxylic acids.

    Science.gov (United States)

    Janecek, Jiri; Paricaud, Patrice

    2012-07-12

    A new thermodynamic approach based on the Sear and Jackson association theory for doubly bonded dimers [Mol. Phys.1994, 82, 1033] is proposed to describe the thermodynamic properties of carboxylic acids. The new model is able to simultaneously represent the vapor pressures, saturated densities, and vaporization enthalpies of the shortest acids and is in a much better agreement with experimental data than other approaches that do no consider the formation of cyclic dimers. The new model is applied to mixtures of carboxylic acids with nonassociating compounds, and a very good description of the vapor-liquid equilibria in mixtures of alkanes + carboxylic acids is obtained.

  19. The acrylonitrile dimer ion: A study of its dissociation via self-catalysis, self-protonation and cyclization into the pyrimidine radical cation

    NARCIS (Netherlands)

    Ervasti, H.K.; Jobst, K.J.; Burgers, P.C.; Ruttink, P.J.A.; Terlouw, J.K.

    2007-01-01

    Large energy barriers prohibit the rearrangement of solitary acrylonitrile ions, CH2CHCN+, into their more stable hydrogen-shift isomers CH2CCNH+ or CHCH–CNH+. This prompted us to examine if these isomerizations occur by self-catalysis in acrylonitrile dimer ions. Such ions, generated by chemical

  20. Trion and dimer formation in three-color fermions

    Science.gov (United States)

    Pohlmann, J.; Privitera, A.; Titvinidze, I.; Hofstetter, W.

    2013-02-01

    We study the problem of three ultracold fermions in different hyperfine states loaded into a lattice with spatial dimension D=1,2. We consider SU(3)-symmetric attractive interactions and also eventually include a three-body constraint, which mimics the effect of three-body losses in the strong-loss regime. We combine exact diagonalization with the Lanczos algorithm, and evaluate both the eigenvalues and the eigenstates of the problem. In D=1, we find that the ground state is always a three-body bound state (trion) for arbitrarily small interaction, while in D=2, due to the stronger influence of finite-size effects, we are not able to provide conclusive evidence of the existence of a finite threshold for trion formation. Our data are, however, compatible with a threshold value which vanishes logarithmically with the size of the system. Moreover, we are able to identify the presence of a fine structure inside the spectrum, which is associated with off-site trionic states. The characterization of these states shows that only the long-distance behavior of the eigenstate wave functions provides clear-cut signatures about the nature of bound states and that on-site observables are not enough to discriminate between them. The inclusion of a three-body constraint due to losses promotes these off-site trions to the role of lowest-energy states, at least in the strong-coupling regime.

  1. Importance of dimer formation of myocardin family members in the regulation of their nuclear export.

    Science.gov (United States)

    Hayashi, Ken'ichiro; Morita, Tsuyoshi

    2013-01-01

    Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.

  2. Formation of covalent di-tyrosine dimers in recombinant α-synuclein

    DEFF Research Database (Denmark)

    van Maarschalkerweerd, A; Pedersen, MN; Peterson, H

    2015-01-01

    Parkinson's disease is associated with fibril deposition in the diseased brain. Misfolding events of the intrinsically disordered synaptic protein α-synuclein are suggested to lead to the formation of transient oligomeric and cytotoxic species. The etiology of Parkinson's disease is further...... associated with mitochondrial dysfunction and formation of reactive oxygen species. Oxidative stress causes chemical modification of native α-synuclein, plausibly further influencing misfolding events. Here, we present evidence for the spontaneous formation of covalent di-tyrosine α-synuclein dimers...

  3. Formation of the Ras dimer is essential for Raf-1 activation.

    Science.gov (United States)

    Inouye, K; Mizutani, S; Koide, H; Kaziro, Y

    2000-02-11

    Although it is well established that Ras requires membrane localization for activation of its target molecule, Raf-1, the reason for this requirement is not fully understood. In this study, we found that modified Ras, which is purified from Sf9 cells, could activate Raf-1 in a cell-free system, when incorporated into liposome. Using a bifunctional cross-linker and a protein-fragmentation complementation assay, we detected dimer formation of Ras in the liposome and in the intact cells, respectively. These results suggest that dimerization of Ras in the lipid membrane is essential for activation of Raf-1. To support this, we found that, when fused to glutathione S-transferase (GST), unprocessed Ras expressed in Escherichia coli could bypass the requirement for liposome. A Ras-dependent Raf-1 activator, which we previously reported (Mizutani, S., Koide, H., and Kaziro, Y. (1998) Oncogene 16, 2781-2786), was still required for Raf-1 activation by GST-Ras. Furthermore, an enforced dimerization of unmodified oncogenic Ras mutant in human embryonic kidney (HEK) 293 cells, using a portion of gyrase B or estrogen receptor, also resulted in activation of Raf-1. From these results, we conclude that membrane localization allows Ras to form a dimer, which is essential, although not sufficient, for Raf-1 activation.

  4. Formation and occurrence of dimer esters of pinene oxidation products in atmospheric aerosols

    Directory of Open Access Journals (Sweden)

    K. Kristensen

    2012-08-01

    Full Text Available Formation of carboxylic acids and dimer esters from α-pinene oxidation were investigated in a smog chamber and in ambient aerosol samples collected during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX. Chamber experiments of α-pinene ozonolysis in dry air and at low NOx concentrations demonstrated formation of two dimer esters, pinyl-diaterpenyl (MW 358 and pinonyl-pinyl dimer ester (MW 368, under both low and high temperature conditions. Concentration levels of the pinyl-diaterpenyl dimer ester were lower than the assumed first-generation oxidation products cis-pinic and terpenylic acids, but similar to the second-generation oxidation products 3-methyl-1,2,3-butane tricarboxylic acid (MBTCA and diaterpenylic acid acetate (DTAA. Dimer esters were observed within the first 30 min, indicating rapid production simultaneous to their structural precursors. However, the sampling time resolution precluded conclusive evidence regarding formation from gas- or particle-phase processes. CCN activities of the particles formed in the smog chamber displayed a modest variation during the course of experiments with κ values in the range 0.06–0.09 (derived at a supersaturation of 0.19%.

    The pinyl-diaterpenyl dimer ester was also observed in ambient aerosol samples collected above a ponderosa pine forest in the Sierra Nevada Mountains of California during two seasonally distinct field campaigns in September 2007 and July 2009. The pinonyl-pinyl ester was observed for the first time in ambient air during the 2009 campaign, and although present at much lower concentrations, it was correlated with the abundance of the pinyl-diaterpenyl ester suggesting similarities in their formation. The maximum concentration of the pinyl-diaterpenyl ester was almost 10 times higher during the warmer 2009 campaign relative to 2007, while the concentration of cis-pinic acid was approximately the same during both

  5. Oncogenic Mutations Differentially Affect Bax Monomer, Dimer, and Oligomeric Pore Formation in the Membrane

    Science.gov (United States)

    Zhang, Mingzhen; Zheng, Jie; Nussinov, Ruth; Ma, Buyong

    2016-09-01

    Dysfunction of Bax, a pro-apoptotic regulator of cellular metabolism is implicated in neurodegenerative diseases and cancer. We have constructed the first atomistic models of the Bax oligomeric pore consisting with experimental residue-residue distances. The models are stable, capturing well double electron-electron resonance (DEER) spectroscopy measurements and provide structural details in line with the DEER data. Comparison with the latest experimental results revealed that our models agree well with both Bax and Bak pores, pointed to a converged structural arrangement for Bax and Bak pore formation. Using multi-scale molecular dynamics simulations, we probed mutational effects on Bax transformation from monomer → dimer → membrane pore formation at atomic resolution. We observe that two cancer-related mutations, G40E and S118I, allosterically destabilize the monomer and stabilize an off-pathway swapped dimer, preventing productive pore formation. This observation suggests a mechanism whereby the mutations may work mainly by over-stabilizing the monomer → dimer transformation toward an unproductive off-pathway swapped-dimer state. Our observations point to misfolded Bax states, shedding light on the molecular mechanism of Bax mutation-elicited cancer. Most importantly, the structure of the Bax pore facilitates future study of releases cytochrome C in atomic detail.

  6. Molecular recognition in different environments: β-cyclodextrin dimer formation in organic solvents.

    Science.gov (United States)

    Zhang, Haiyang; Tan, Tianwei; Feng, Wei; van der Spoel, David

    2012-10-25

    Electrostatic and van der Waals interactions as well as entropy contribute to the energetics governing macromolecular complexation in biomolecules. Hydrogen bonds play a particularly important role in such interactions. Here we use molecular dynamics (MD) simulations to investigate the hydrogen bond (HB) orientations of free beta-cyclodextrin (β-CD) and head-to-head dimerization of β-CD monomers with and without guest molecules in different environments, namely, in 10 different solvents covering a wide range of polarity. Potentials of mean force for the dimer dissociation are derived from umbrella sampling simulations, allowing determination of the binding affinity between monomers. The HB orientations are in good agreement with available experimental data in water and dimethyl sulfoxide, yielding confidence in the force field used. HB exchanges at the secondary rim of β-CD are observed with a fast rate in water and with a low rate or even no exchange in other solvents. Orientational preferences of interglucopyranose HBs and their effects on the β-CD structure in these solvents are discussed in detail. Polar solvents with stronger HB accepting abilities can interrupt intermolecular HBs more easily, resulting in a less stable dimer. Guest molecules included in the channel-type cavity strengthen the binding affinity between two monomers to some extent, particularly in polar solvents. Formation of the head-to-head dimer is therefore solvent-dependent and guest-modulated. There is only limited correlation between the dimer binding energies and solvent properties like the dielectric constant. This implies that implicit solvent models will not be capable of predicting important properties like binding energy for other solvents than water without a complete reparameterization. This work provides a deeper comprehension on the properties of β-CD, and implications for the application of cyclodextrins in aqueous and nonaqueous media are discussed.

  7. Formation of cyclobutane thymine dimers from UVA photosensitization of pyridopsoralen monoadducted DNA

    Energy Technology Data Exchange (ETDEWEB)

    Guillo, L.A. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica; Beylot, B.; Spassky, A. [Paris-5 Univ., 75 (France); Vigny, P. [Centre de Biophysique Moleculaire, Orleans (France)

    1996-08-01

    The present report provides evidence that thymine dimerization can be UVA photosensitized at a tetranucleotide, 5`-TATT-3`, by a 7-methyl-pyrido(3,4-c)psoralen monoadduct in DNA. The efficiency of the photoprocess depends on the tetranucleotide flanking sequences. These results demonstrate that one DNA lesion can originate the contigious formation of a second type of lesion and emphasize the sequence-specific response to interaction of drugs with DNA. Results are related to the sensitivity of DNA to 1,10-phenanthroline-cuprous ion complex nucleolytic activity and discussed in terms of the major role of local deformability of DNA in interaction with ligands. (author).

  8. Photoinduced formation of an azobenzene-based CD-active supramolecular cyclic dimer.

    Science.gov (United States)

    Sogawa, Hiromitsu; Terada, Kayo; Miyagi, Yu; Shiotsuki, Masashi; Inai, Yoshihito; Masuda, Toshio; Sanda, Fumio

    2015-04-27

    A series of new photo-responsive amino acid-derived azobenzenedicarboxylic acid derivatives (S)-1 a-e were synthesized. Compound (S)-1 a in the trans form exhibited no circular dichroism (CD) signal in DMF under ambient conditions, whereas intense Cotton effects were observed upon UV irradiation, indicating the formation of a chiral supramolecular structure in the cis form. The CD signals disappeared when trifluoroacetic acid (TFA) was added to the solution. The ester counterpart [(S)-1 a'] showed no CD signal. Hydrogen bonding between the carboxy groups seemed necessary for constructing the supramolecular structure. The kinetic studies of cis to trans isomerization of (S)-1 a demonstrated that the formation of a chiral supramolecule enhances the stability of the cis-azobenzene structure. The ESI mass spectrum of stilbenedicarboxylic acid (S)-4, an analogue of (S)-1 b, confirmed the formation of a dimer. A theoretical CD study revealed that (S)-1 a in the cis form should be present as a cyclic chiral dimer.

  9. Purine and pyrimidine metabolism.

    Science.gov (United States)

    Zöllner, N

    1982-09-01

    The pathways of purine biosynthesis and degradation have been elucidated during the last 30 years; the regulation of the mechanisms involved is not yet fully understood, particularly with respect to quantitative aspects. Research into inborn errors of purine metabolism has provided valuable insights into purine synthesis and salvage pathways. Nutrition experiments using purine-free formula diets and supplements with defined purine sources permit precise descriptions of the influence of various dietary purines on uric acid formation. Supplements of dietary purines produce dose-proportional increases in plasma uric acid concentrations, uric acid pool size and renal uric acid excretion. The magnitude of these increases depends on the type of purine compound administered, which may limit the value of food tables for human dietetics. Purine content of food must be related not only to weight but also to energy and to protein, particularly if new foodstuffs or a vegetarian diet are ingested. Dietary purines appear to influence the biosynthesis of pyrimidines. In contrast to dietary purines, pyrimidines in the diet, if administered as nucleosides or nucleotides, are utilized in animals for the synthesis of nucleic acids. Much further work is necessary for a better understanding of the inter-relationships of purine and pyrimidine metabolism.

  10. Amyloid-beta(29-42) dimer formations studied by a multicanonical-multioverlap molecular dynamics simulation.

    Science.gov (United States)

    Itoh, Satoru G; Okamoto, Yuko

    2008-03-13

    Amyloid-beta peptides are known to form amyloid fibrils and are considered to play an important role in Alzheimer's disease. Amyloid-beta(29-42) is a fragment of the amyloid-beta peptide and also has a tendency to form amyloid fibrils. In order to study the mechanism of amyloidogenesis of this fragment, we applied one of the generalized-ensemble algorithms, the multicanonical-multioverlap algorithm, to amyloid-beta(29-42) dimer in aqueous solution. We obtained a detailed free-energy landscape of the dimer system. From the detailed free-energy landscape, we examined monomer and dimer formations of amyloid-beta(29-42) and deduced dimerization processes, which correspond to seeding processes in the amyloidogenesis of amyloid-beta(29-42).

  11. p53 mutant human glioma cells are sensitive to UV-C-induced apoptosis due to impaired cyclobutane pyrimidine dimer removal.

    Science.gov (United States)

    Batista, Luis F Z; Roos, Wynand P; Kaina, Bernd; Menck, Carlos F M

    2009-02-01

    The p53 protein is a key regulator of cell responses to DNA damage, and it has been shown that it sensitizes glioma cells to the alkylating agent temozolomide by up-regulating the extrinsic apoptotic pathway, whereas it increases the resistance to chloroethylating agents, such as ACNU and BCNU, probably by enhancing the efficiency of DNA repair. However, because these agents induce a wide variety of distinct DNA lesions, the direct importance of DNA repair is hard to access. Here, it is shown that the induction of photoproducts by UV light (UV-C) significantly induces apoptosis in a p53-mutated glioma background. This is caused by a reduced level of photoproduct repair, resulting in the persistence of DNA lesions in p53-mutated glioma cells. UV-C-induced apoptosis in p53 mutant glioma cells is preceded by strong transcription and replication inhibition due to blockage by unrepaired photolesions. Moreover, the results indicate that UV-C-induced apoptosis of p53 mutant glioma cells is executed through the intrinsic apoptotic pathway, with Bcl-2 degradation and sustained Bax and Bak up-regulation. Collectively, the data indicate that unrepaired DNA lesions induce apoptosis in p53 mutant gliomas despite the resistance of these gliomas to temozolomide, suggesting that efficiency of treatment of p53 mutant gliomas might be higher with agents that induce the formation of DNA lesions whose global genomic repair is dependent on p53.

  12. Inducible nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers in the cell cycle of the budding yeast Saccharomyces cerevisiae: evidence that inducible NER is confined to the G1 phase of the mitotic cell cycle.

    Science.gov (United States)

    Scott, A D; Waters, R

    1997-03-18

    We previously reported on an inducible component of nucleotide excision repair in Saccharomyces cerevisiae that is controlled by the RAD16 gene. Here we describe a study of this event at the MAT alpha and HML alpha mating-type loci and on the transcribed (TS) and nontranscribed (NTS) strands of the RAD16 gene. Events were examined at various stages of the mitotic cycle in cells synchronised by centrifugal elutriation. Repair of cyclobutane pyrimidine dimers (CPDs) following a single UV dose does not vary significantly in different stages of the mitotic cell cycle. CPDs are removed more rapidly from the transcriptionally active MAT alpha locus than from the silent HML alpha locus, and the TS of RAD16 is repaired faster than the NTS in all stages of the cycle following a single UV irradiation. Enhanced excision of CPDs at MAT alpha and HML alpha can be induced only in the G1 and early S stages of the cell cycle. Here prior irradiation of cells with 25 J/m2 enhances the removal of CPDs following a second UV dose of 70 J/m2. The level of enhancement of repair does not differ significantly between MAT alpha and HML alpha in G1. Enhanced removal of CPDs is absent when cells receive the inducing dose in late S or G2/M. Repair of CPDs in both strands of RAD16 is similarly enhanced only if cells receive the initial irradiation in G1 and early S. The level of enhanced removal of CPDs is not significantly different in the TS and NTS of RAD16 either in asynchronous cells or in cells preirradiated in G1 and early S. It has been shown by others that UV-induced expression of RAD16 remains at high levels if cells are held in G1 by treatment with alpha factor. Therefore the increase in RAD16 transcript levels in G1 may be responsible for the ability to enhance NER solely in this stage of the cell cycle.

  13. Formation and Evolution Mechanism of Plasmon Resonance from Single Ring-Shaped Nanotube to Dimer and Arrays

    Directory of Open Access Journals (Sweden)

    F. Q. Zhou

    2014-01-01

    Full Text Available The formation and evolution mechanisms of plasmon resonance from single Ring-shaped nanotube to dimer and arrays are studied; an attempt has been made to bridge the gap between single-tube, dimer, and array. Results show that resonant modes can be divided into three types: quadrupole, hexapole, and octupole resonance from visible to near infrared region, and each mode maintains relatively stable resonant characteristics, but the optical transmission properties including redshift and blueshift of the modes and band gap are highly tunable by adjusting the number of nanotube and intertube spacing values. The field-interference mechanism has been suggested to explain the physical origin.

  14. Sulfur dimers adsorbed on Au(111) as building blocks for sulfur octomers formation: A density functional study

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez-Tamargo, Carlos E.; Montero-Alejo, Ana Lilian [Laboratory of Computational and Theoretical Chemistry (LQCT), Faculty of Chemistry, Havana University, Havana 10400 (Cuba); Pujals, Daniel Codorniu [Higher Institute of Technologies and Applied Sciences (InSTEC), Havana 10400 (Cuba); Mikosch, Hans [Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/E164-EC, 1060 Vienna (Austria); Hernández, Mayra P., E-mail: mayrap@imre.oc.uh.cu [Instituto de Ciencias y Tecnologías de Materiales (IMRE), Havana 10400 (Cuba)

    2014-07-28

    Experimental scanning tunneling microscopy (STM) studies have shown for more than two decades rectangular formations when sulfur atoms are deposited on Au(111) surfaces. The precursors have ranged from simple molecules or ions, such as SO{sub 2} gas or sulfide anions, to more complex organosulfur compounds. We investigated, within the framework of the Density Functional Theory, the structure of these rectangular patterns assuming them entirely composed of sulfur atoms as the experimental evidence suggests. The sulfur coverage at which the simulations were carried out (0.67 ML or higher) provoked that the sulfur-sulfur association had to be taken into account for achieving a good agreement between the sets of simulated and experimental STM images. A combination of four sulfur dimers per rectangular formation properly explained the trends obtained by the experimental STM analysis which were related with the rectangles' size and shape fluctuations together with sulfur-sulfur distances within these rectangles. Finally, a projected density of states analysis showed that the dimers were capable of altering the Au(5d) electronic states at the same level as atomic sulfur adsorbed at low coverage. Besides, sulfur dimers states were perfectly distinguished, whose presence near and above the Fermi level can explain both: sulfur-sulfur bond elongation and dimers stability when they stayed adsorbed on the surface at high coverage.

  15. A study about dimers formation of formic acid in gas phase and in the valence region

    Energy Technology Data Exchange (ETDEWEB)

    Arruda, M.S. [Universidade Federal do Reconcavo da Bahia (UFRB), Amargosa, BA (Brazil); Prudente, F.V.; Marinho, R.R.T.; Nascimento, E.M. [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil)

    2012-07-01

    Full text: Study of simple pre-biotic molecules takes great importance for understanding about complex organic molecules formation like amino acids, proteins and nucleobases within the DNA and RNA. A hypothesis for the appearance of nucleobases is that they could have been synthesized from simpler organic composites contained in interstellar medium (ISM), meteorites and asteroids. Lots of experiments have demonstrated that it is possible to produce complex pre-biotic molecules from simpler molecules under environments that simulate the ISM. Thus, we have performed a theoretical and experimental study about photoionization and photofragmentation processes of simple pre-biotic molecules that are important in the synthesis of complex biomolecules. In this work particularly, we performed photoionization and photofragmentation process of formic acid-D2 (CDOOD) in order to verify if some molecular fragmentations coming from dimers that could be formed before ionization region at TOF mass spectrometer. Experimentally, we measured these molecules mass spectra in gaseous phase. These spectra were got as function of pressures in experimental chamber, temperature samples and photon energy, in the vacuum ultraviolet region, between 11 and 20 eV. These data had been obtained in the Brazilian Laboratory of Synchrotron Light, by using mass spectrometer of flight time. The mass spectra had been obtained by using the photoelectron photoion coincidence technique, PEPICO. For a better understanding of experimental results, we have made a theoretical analysis of the photofragmentation by using Density Functional Theory. (author)

  16. Hydrogen sulfide reduces RAGE toxicity through inhibition of its dimer formation.

    Science.gov (United States)

    Zhou, Hong; Ding, Lei; Wu, Zhiyuan; Cao, Xu; Zhang, Qichun; Lin, Li; Bian, Jin-Song

    2017-03-01

    RAGE is important in the development of neurodegenerative diseases. The present study was designed to investigate the effect of hydrogen sulfide (H2S, an endogenous gaseous mediator) on the cytotoxicity caused by RAGE activation during the chronic oxidative stress. Aβ1-42 decreased cell viability and induced cell senescence in SH-SY5Y cells. Treatment with advanced glycation end products (AGEs) induced cell injury in HEK293 cells stably expressing RAGE (HEK293-RAGE) and stimulated inflammatory responses in SH-SY5Y cells. Pretreatment of SH-SY5Y cells with an H2S donor, NaHS, significantly attenuated the above harmful effects caused by Aβ1-42 or AGEs. Western blotting analysis shows that oxidative stress enhanced RAGE protein expression which was attenuated by either NaHS or over-expression of cystathionine β-synthase (CBS), a critical enzyme for producing H2S in brain cells. Both Western blots and split GFP complementation analysis demonstrate that NaHS reduced H2O2-enhanced RAGE dimerization. Immunofluorescence analysis shows that H2O2 up-regulated the membrane expression of wild-type RAGE. However, H2O2-enhanced expression of the RAGE harboring C259S/C310S double mutation (DM-RAGE) was observed in the endoplasmic reticulum. Treatment with NaHS attenuated the effects of H2O2 on the protein expression of WT-RAGE, but not that of DM-RAGE. Cycloheximide chase and ubiquitination assays show that NaHS reduced the half-life of WT-RAGE to a similar level of DM-RAGE. S-sulfhydration assay with the tag-switch technique demonstrate that H2S may directly S-sulfhydrate the C259/C301 residues. Our data suggest that H2S reduces RAGE dimer formation and impairs its membrane stability. The lowered plasma membrane abundance of RAGE therefore helps to protect cells against various RAGE mediated pathological effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Base pairing enhances fluorescence and favors cyclobutane dimer formation induced upon absorption of UVA radiation by DNA.

    Science.gov (United States)

    Banyasz, Akos; Vayá, Ignacio; Changenet-Barret, Pascale; Gustavsson, Thomas; Douki, Thierry; Markovitsi, Dimitra

    2011-04-13

    The photochemical properties of the DNA duplex (dA)(20)·(dT)(20) are compared with those of the parent single strands. It is shown that base pairing increases the probability of absorbing UVA photons, probably due to the formation of charge-transfer states. UVA excitation induces fluorescence peaking at ∼420 nm and decaying on the nanosecond time scale. The fluorescence quantum yield, the fluorescence lifetime, and the quantum yield for cyclobutane dimer formation increase upon base pairing. Such behavior contrasts with that of the UVC-induced processes.

  18. Formation of H-type liquid crystal dimer at air-water interface

    Energy Technology Data Exchange (ETDEWEB)

    Karthik, C., E-mail: karthik.c@pilani.bits-pilani.ac.in; Gupta, Adbhut, E-mail: karthik.c@pilani.bits-pilani.ac.in; Joshi, Aditya, E-mail: karthik.c@pilani.bits-pilani.ac.in; Manjuladevi, V., E-mail: karthik.c@pilani.bits-pilani.ac.in; Gupta, Raj Kumar, E-mail: karthik.c@pilani.bits-pilani.ac.in [Department of Physics, Birla Institute of Technology and Science, Pilani, Rajasthan -333031 (India); Varia, Mahesh C.; Kumar, Sandeep [Raman Research Institute, Sadashivanagar, Bangalore - 560080 (India)

    2014-04-24

    We have formed the Langmuir monolayer of H-shaped Azo linked liquid crystal dimer molecule at the air-water interface. Isocycles of the molecule showed hysteresis suggesting the ir-reversible nature of the monolayer formed. The thin film deposited on the silicon wafer was characterized using Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscopy (FESEM). The images showed uniform domains of the dimer molecule. We propose that these molecules tend to take book shelf configuration in the liquid phase.

  19. Influence of cyclic dimer formation on the phase behavior of carboxylic acids. II. Cross-associating systems.

    Science.gov (United States)

    Janeček, Jiří; Paricaud, Patrice

    2013-08-15

    The doubly bonded dimer association scheme (DBD) proposed by Sear and Jackson is extended to mixtures exhibiting both self- and cross-associations. The PC-SAFT equation of state is combined with the new DBD association contribution to describe the vapor-liquid equilibria of binary mixtures of carboxylic acids + associating compounds (water, alcohols, and carboxylic acids). The effect of doubly bonded dimers on the phase behavior in such systems is less important than in mixtures of carboxylic acids with nonassociating compounds, due to the cross-associations that compete with the formation of DBDs. Nevertheless, a clear improvement in the description of vapor-liquid coexistence curves is achieved over the classical 2B association model, particularly for the dew point curves.

  20. Strongly frustrated triangular spin lattice emerging from triplet dimer formation in honeycomb Li2IrO3

    Science.gov (United States)

    Nishimoto, Satoshi; Katukuri, Vamshi M.; Yushankhai, Viktor; Stoll, Hermann; Rößler, Ulrich K.; Hozoi, Liviu; Rousochatzakis, Ioannis; van den Brink, Jeroen

    2016-01-01

    Iridium oxides with a honeycomb lattice have been identified as platforms for the much anticipated Kitaev topological spin liquid: the spin-orbit entangled states of Ir4+ in principle generate precisely the required type of anisotropic exchange. However, other magnetic couplings can drive the system away from the spin-liquid phase. With this in mind, here we disentangle the different magnetic interactions in Li2IrO3, a honeycomb iridate with two crystallographically inequivalent sets of adjacent Ir sites. Our ab initio many-body calculations show that, while both Heisenberg and Kitaev nearest-neighbour couplings are present, on one set of Ir-Ir bonds the former dominates, resulting in the formation of spin-triplet dimers. The triplet dimers frame a strongly frustrated triangular lattice and by exact cluster diagonalization we show that they remain protected in a wide region of the phase diagram.

  1. Triplet formation involving a polar transition state in a well-defined intramolecular perylenediimide dimeric aggregate

    NARCIS (Netherlands)

    D. Veldman; S.M.A. Chopin; S.C.J. Meskers; M.M. Groeneveld; R.M. Williams; R.A.J. Janssen

    2008-01-01

    A cofacially stacked perylenediimide (PDI) dimer with a xanthene linker was studied under a variety of conditions (solvent, temperature) and serves as a model for the molecular interactions occurring in solid films. Intrinsically, the PDI units have a fluorescence quantum yield (Phi(F)) close to uni

  2. Electronic excited states responsible for dimer formation upon UV absorption directly by thymine strands: joint experimental and theoretical study.

    Science.gov (United States)

    Banyasz, Akos; Douki, Thierry; Improta, Roberto; Gustavsson, Thomas; Onidas, Delphine; Vayá, Ignacio; Perron, Marion; Markovitsi, Dimitra

    2012-09-12

    The study addresses interconnected issues related to two major types of cycloadditions between adjacent thymines in DNA leading to cyclobutane dimers (TTs) and (6-4) adducts. Experimental results are obtained for the single strand (dT)(20) by steady-state and time-resolved optical spectroscopy, as well as by HPLC coupled to mass spectrometry. Calculations are carried out for the dinucleoside monophosphate in water using the TD-M052X method and including the polarizable continuum model; the reliability of TD-M052X is checked against CASPT2 calculations regarding the behavior of two stacked thymines in the gas phase. It is shown that irradiation at the main absorption band leads to cyclobutane dimers (TTs) and (6-4) adducts via different electronic excited states. TTs are formed via (1)ππ* excitons; [2 + 2] dimerization proceeds along a barrierless path, in line with the constant quantum yield (0.05) with the irradiation wavelength, the contribution of the (3)ππ* state to this reaction being less than 10%. The formation of oxetane, the reaction intermediate leading to (6-4) adducts, occurs via charge transfer excited states involving two stacked thymines, whose fingerprint is detected in the fluorescence spectra; it involves an energy barrier explaining the important decrease in the quantum yield of (6-4) adducts with the irradiation wavelength.

  3. Fibroblast growth factor 2 dimer with superagonist in vitro activity improves granulation tissue formation during wound healing.

    Science.gov (United States)

    Decker, Caitlin G; Wang, Yu; Paluck, Samantha J; Shen, Lu; Loo, Joseph A; Levine, Alex J; Miller, Lloyd S; Maynard, Heather D

    2016-03-01

    Site-specific chemical dimerization of fibroblast growth factor 2 (FGF2) with the optimal linker length resulted in a FGF2 homodimer with improved granulation tissue formation and blood vessel formation at exceptionally low concentrations. Homodimers of FGF2 were synthesized through site-specific linkages to both ends of different molecular weight poly(ethylene glycols) (PEGs). The optimal linker length was determined by screening dimer-induced metabolic activity of human dermal fibroblasts and found to be that closest to the inter-cysteine distance, 70 Å, corresponding to 2 kDa PEG. A straightforward analysis of the kinetics of second ligand binding as a function of tether length showed that, as the polymerization index (the number of monomer repeat units in the polymer, N) of the tether decreases, the mean time for second ligand capture decreases as ∼N(3/2), leading to an enhancement of the number of doubly bound ligands in steady-state for a given (tethered) ligand concentration. FGF2-PEG2k-FGF2 induced greater fibroblast metabolic activity than FGF2 alone, all other dimers, and all monoconjugates, at each concentration tested, with the greatest difference observed at low (0.1 ng/mL) concentration. FGF2-PEG2k-FGF2 further exhibited superior activity compared to FGF2 for both metabolic activity and migration in human umbilical vein endothelial cells, as well as improved angiogenesis in a coculture model in vitro. Efficacy in an in vivo wound healing model was assessed in diabetic mice. FGF2-PEG2k-FGF2 increased granulation tissue and blood vessel density in the wound bed compared to FGF2. The results suggest that this rationally designed construct may be useful for improving the fibroblast matrix formation and angiogenesis in chronic wound healing.

  4. Nitrobenzene anti-parallel dimer formation in non-polar solvents

    Directory of Open Access Journals (Sweden)

    Toshiyuki Shikata

    2014-06-01

    Full Text Available We investigated the dielectric and depolarized Rayleigh scattering behaviors of nitrobenzene (NO2-Bz, which is a benzene mono-substituted with a planar molecular frame bearing the large electric dipole moment 4.0 D, in non-polar solvents solutions, such as tetrachloromethane and benzene, at up to 3 THz for the dielectric measurements and 8 THz for the scattering experiments at 20 °C. The dielectric relaxation strength of the system was substantially smaller than the proportionality to the concentration in a concentrated regime and showed a Kirkwood correlation factor markedly lower than unity; gK ∼ 0.65. This observation revealed that NO2-Bz has a tendency to form dimers, (NO2-Bz2, in anti-parallel configurations for the dipole moment with increasing concentration of the two solvents. Both the dielectric and scattering data exhibited fast and slow Debye-type relaxation modes with the characteristic time constants ∼7 and ∼50 ps in a concentrated regime (∼15 and ∼30 ps in a dilute regime, respectively. The fast mode was simply attributed to the rotational motion of the (monomeric NO2-Bz. However, the magnitude of the slow mode was proportional to the square of the concentration in the dilute regime; thus, the mode was assigned to the anti-parallel dimer, (NO2-Bz2, dissociation process, and the slow relaxation time was attributed to the anti-parallel dimer lifetime. The concentration dependencies of both the dielectric and scattering data show that the NO2-Bz molecular processes are controlled through a chemical equilibrium between monomers and anti-parallel dimers, 2NO2-Bz ↔ (NO2-Bz2, due to a strong dipole-dipole interaction between nitro groups.

  5. Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation.

    Science.gov (United States)

    Kronqvist, Nina; Otikovs, Martins; Chmyrov, Volodymyr; Chen, Gefei; Andersson, Marlene; Nordling, Kerstin; Landreh, Michael; Sarr, Médoune; Jörnvall, Hans; Wennmalm, Stefan; Widengren, Jerker; Meng, Qing; Rising, Anna; Otzen, Daniel; Knight, Stefan D; Jaudzems, Kristaps; Johansson, Jan

    2014-01-01

    The mechanisms controlling the conversion of spider silk proteins into insoluble fibres, which happens in a fraction of a second and in a defined region of the silk glands, are still unresolved. The N-terminal domain changes conformation and forms a homodimer when pH is lowered from 7 to 6; however, the molecular details still remain to be determined. Here we investigate site-directed mutants of the N-terminal domain from Euprosthenops australis major ampullate spidroin 1 and find that the charged residues D40, R60 and K65 mediate intersubunit electrostatic interactions. Protonation of E79 and E119 is required for structural conversions of the subunits into a dimer conformation, and subsequent protonation of E84 around pH 5.7 leads to the formation of a fully stable dimer. These residues are highly conserved, indicating that the now proposed three-step mechanism prevents premature aggregation of spidroins and enables fast formation of spider silk fibres in general.

  6. Pyrimidine-pyridine ring interconversion

    NARCIS (Netherlands)

    Plas, van der H.C.

    2003-01-01

    This chapter discusses the pyrimidine-to-pyridine ring transformation and pyridine-to-pyrimidine ring transformation. In nucleophile-induced pyrimidine-to-pyridine rearrangements, two types of reactions can be distinguished depending on the structure of the nucleophile: (1) reactions in which the ni

  7. The ATP-dependent remodeler RSC transfers histone dimers and octamers through the rapid formation of an unstable encounter intermediate.

    Science.gov (United States)

    Rowe, Claire E; Narlikar, Geeta J

    2010-11-16

    RSC, an essential chromatin remodeling complex in budding yeast, is involved in a variety of biological processes including transcription, recombination, repair, and replication. How RSC participates in such diverse processes is not fully understood. In vitro, RSC uses ATP to carry out several seemingly distinct reactions: it repositions nucleosomes, transfers H2A/H2B dimers between nucleosomes, and transfers histone octamers between pieces of DNA. This raises the intriguing mechanistic question of how this molecular machine can use a single ATPase subunit to create these varied products. Here, we use a FRET-based approach to kinetically order the products of the RSC reaction. Surprisingly, transfer of H2A/H2B dimers and histone octamers is initiated on a time scale of seconds when assayed by FRET, but formation of stable nucleosomal products occurs on a time scale of minutes when assayed by native gel. These results suggest a model in which RSC action rapidly generates an unstable encounter intermediate that contains the two exchange substrates in close proximity. This intermediate then collapses more slowly to form the stable transfer products seen on native gels. The rapid, biologically relevant time scale on which the transfer products are generated implies that such products can play key roles in vivo.

  8. The acrylonitrile dimer ion

    Science.gov (United States)

    Ervasti, Henri K.; Jobst, Karl J.; Burgers, Peter C.; Ruttink, Paul J. Ae; Terlouw, Johan K.

    2007-04-01

    Large energy barriers prohibit the rearrangement of solitary acrylonitrile ions, CH2CHCN+, into their more stable hydrogen-shift isomers CH2CCNH+ or CHCH-CNH+. This prompted us to examine if these isomerizations occur by self-catalysis in acrylonitrile dimer ions. Such ions, generated by chemical ionization experiments of acrylonitrile with an excess of carbon dioxide, undergo five dissociations in the [mu]s time frame, as witnessed by peaks at m/z 53, 54, 79, 80 and 105 in their metastable ion mass spectrum. Collision experiments on these product ions, deuterium labeling, and a detailed computational analysis using the CBS-QB3 model chemistry lead to the following conclusions: (i) the m/z 54 ions are ions CH2CHCNH+ generated by self-protonation in ion-dipole stabilized hydrogen-bridged dimer ions [CH2CHCN...H-C(CN)CH2]+ and [CH2CHCN...H-C(H)C(H)CN]+; the proton shifts in these ions are associated with a small reverse barrier; (ii) dissociation of the H-bridged ions into CH2CCNH+ or CHCH-CNH+ by self-catalysis is energetically feasible but kinetically improbable: experiment shows that the m/z 53 ions are CH2CHCN+ ions, generated by back dissociation; (iii) the peaks at m/z 79, 80 and 105 correspond with the losses of HCN, C2H2 and H, respectively. The calculations indicate that these ions are generated from dimer ions that have adopted the (much more stable) covalently bound "head-to-tail" structure [CH2CHCN-C(H2)C(H)CN]+; experiments indicate that the m/z 79 (C5H5N) and m/z 105 (C6H6N2) ions have linear structures but the m/z 80 (C4H4N2) ions consist of ionized pyrimidine in admixture with its stable pyrimidine-2-ylidene isomer. Acrylonitrile is a confirmed species in interstellar space and our study provides experimental and computational evidence that its dimer radical cation yields the ionized prebiotic pyrimidine molecule.

  9. Biofilm formation and antibiotic production in Ruegeria mobilis are influenced by intracellular concentrations of cyclic dimeric guanosinmonophosphate.

    Science.gov (United States)

    D'Alvise, Paul W; Magdenoska, Olivera; Melchiorsen, Jette; Nielsen, Kristian F; Gram, Lone

    2014-05-01

    In many species of the marine Roseobacter clade, periods of attached life, in association with phytoplankton or particles, are interspersed with planktonic phases. The purpose of this study was to determine whether shifts between motile and sessile life in the globally abundant Roseobacter clade species Ruegeria mobilis are associated with intracellular concentrations of the signal compound cyclic dimeric guanosinmonophosphate (c-di-GMP), which in bacteria regulates transitions between motile and sessile life stages. Genes for diguanylate cyclases and phosphodiesterases, which are involved in c-di-GMP signalling, were found in the genome of R. mobilis strain F1926. Ion pair chromatography-tandem mass spectrometry revealed 20-fold higher c-di-GMP concentrations per cell in biofilm-containing cultures than in planktonic cells. An introduced diguanylate cyclase gene increased c-di-GMP and enhanced biofilm formation and production of the potent antibiotic tropodithietic acid (TDA). An introduced phosphodiesterase gene decreased c-di-GMP and reduced biofilm formation and TDA production. tdaC, a key gene for TDA biosynthesis, was expressed only in attached or biofilm-forming cells, and expression was induced immediately after initial attachment. In conclusion, c-di-GMP signalling controls biofilm formation and biofilm-associated traits in R. mobilis and, as suggested by presence of GGDEF and EAL domain protein genes, also in other Roseobacter clade species. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Signal peptide peptidase (SPP dimer formation as assessed by fluorescence lifetime imaging microscopy (FLIM in intact cells

    Directory of Open Access Journals (Sweden)

    Nyborg Andrew C

    2006-11-01

    Full Text Available Abstract Background Signal peptide peptidase (SPP is an intramembrane cleaving protease identified by its cleavage of several type II membrane signal peptides. Conservation of intramembrane active site residues demonstrates that SPP, SPP family members, and presenilins (PSs make up a family of intramembrane cleaving proteases. Because SPP appears to function without additional protein cofactors, the study of SPP may provide structural insights into the mechanism of intramembrane proteolysis by this biomedically important family of proteins. Previous studies have shown that SPP isolated from cells appears to be a homodimer, but some evidence exists that in vitro SPP may be active as a monomer. We have conducted additional experiments to determine if SPP exists as a monomer or dimer in vivo. Results Fluorescence lifetime imaging microscopy (FLIM can be is used to determine intra- or intermolecular interactions by fluorescently labeling epitopes on one or two different molecules. If the donor and acceptor fluorophores are less than 10 nm apart, the donor fluorophore lifetime shortens proportionally to the distance between the fluorophores. In this study, we used two types of fluorescence energy transfer (FRET pairs; cyan fluorescent protein (CFP with yellow fluorescent protein (YFP or Alexa 488 with Cy3 to differentially label the NH2- or COOH-termini of SPP molecules. A cell based SPP activity assay was used to show that all tagged SPP proteins are proteolytically active. Using FLIM we were able to show that the donor fluorophore lifetime of the CFP tagged SPP construct in living cells significantly decreases when either a NH2- or COOH-terminally YFP tagged SPP construct is co-transfected, indicating close proximity between two different SPP molecules. These data were then confirmed in cell lines stably co-expressing V5- and FLAG-tagged SPP constructs. Conclusion Our FLIM data strongly suggest dimer formation between two separate SPP proteins

  11. How to link pyrene to its host lipid to minimize the extent of membrane perturbations and to optimize pyrene dimer formation

    DEFF Research Database (Denmark)

    Franova, M. D.; Repakova, J.; Holopainen, J. M.;

    2014-01-01

    atomistic molecular dynamics simulations to consider membranes where pyrene moieties are attached to lipid acyl chains in varying positions. We find that in a DOPC bilayer the conformational ordering of lipids around di-pyrenyl-PC probes is altered to a largely similar extent regardless of where the pyrene...... moiety is attached to the hydrocarbon chain. This is in contrast to saturated membranes, where pyrene-induced perturbations have been observed to be more prominent. Meanwhile, the formation of pyrene dimers depends on the linkage point between pyrene and its host lipid. Membrane-spanning dimers between...

  12. Dimer formation in radiation-irradiated aqueous solution of lysozyme studied by light-scattering-intensity measurement

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, S.; Masuda, T.; Kondo, M. (Institute of Physical and Chemical Research, Wako, Saitama (Japan); Tokyo Metropolitan Univ. (Japan). Faculty of Science); Seki, H.; Imamura, M. (Institute of Physical and Chemical Research, Wako, Saitama (Japan))

    1981-07-01

    The reaction of lysozyme with OH radical, Br/sub 2/ anion radical, and e/sup -/sub(aq), produced in an aqueous solution by pulsed electrons and ..gamma..-rays, were investigated. Irradiated enzymes showed an increase in the light scattering intensity (LSI) which is proportional to the absorbed dose. Results obtained from SDS gel electrophoresis confirm dimerization of lysozyme, which is considered to be responsible for the increase in LSI. It was found that the rate constant of the dimerization of protein radicals produced in the reaction with OH radical is 2k = (1.0+-0.3) x 10/sup 6/M/sup -1/s/sup -1/ and the yield of the dimerization is 0.6 in G. The enzymatic activity of the dimer is shown to be reduced to about 30 per cent of that of the intact enzyme. It is concluded that the radiation-induced inactivation of lysozyme is largely due to dimerization.

  13. Dimer formation in radiation-irradiated aqueous solution of lysozyme studied by light-scattering-intensity measurement.

    Science.gov (United States)

    Hashimoto, S; Seki, H; Masuda, T; Imamura, M; Kondo, M

    1981-07-01

    The reaction of lysozyme with OH., Br.-2 and e-aq, produced in an aqueous solution by pulsed electrons and gamma-rays, were investigated. Irradiated enzymes showed an increase in the light scattering intensity (LSI) which is proportional to the absorbed dose. Results obtained from SDS gel electrophoresis confirm dimerization of lysozyme, which is considered to be responsible for the increase in LSI. It was found that the rate constant of the dimerization of protein radicals produced in the reaction with OH. is 2K=(1.0 +/- 0.3) X 10(6)M-1 s-1 and the yield of the dimerization is 0.6 in G. The enzymatic activity of the dimer is shown to be reduced to about 30 per cent of that of the intact enzyme. It is concluded that the radiation-induced inactivation of lysozyme is largely due to dimerization.

  14. Interaction of DDP with bovine serum albumin facilitates formation of the protein dimers

    Science.gov (United States)

    Belaya, I.; Chikhirzhina, E.; Polyanichko, A.

    2017-07-01

    Interaction of bovine serum albumin (BSA) with cis- and trans- isomers of diamminedichloroplatinum(II) (DDP) was studied using electrophoretic analysis and Fourier transformed infrared spectroscopy (FTIR). The application of FTIR spectroscopy allowed us to study the DDP/BSA complexes in D2O solutions using protein concentrations close to the physiological level (30 mg/ml) with platinum to BSA molar ratios in the range of 1:1 to 150:1. Under these conditions we have observed formation of relatively weak non-covalent intermolecular protein complexes, which dominated over the BSA-Pt-BSA crosslinks. Analysis of the IR spectra in the region of amide I‧ band revealed that the fraction of the α-helical regions in the protein decreases from ∼65% to approximately 55% and 48% in the complexes with cis- and trans-DDP respectively, while the amount of extended β-structures increases from ∼15 to 20% in BSA to 20-30% in its complexes with cis-DDP and up to 35-40% in trans-DDP/BSA complexes. Based on the data obtained we conclude that multiple intermolecular interactions take place in the solution facilitated by the changes in the BSA secondary structure, induced by DDP binding.

  15. Thiamin Pyrimidine Biosynthesis in Candida albicans: A Remarkable Reaction between Histidine and Pyridoxal Phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Rung-Yi; Huang, Siyu; Fenwick, Michael K.; Hazra, Amrita; Zhang, Yang; Rajashankar, Kanagalaghatta; Philmus, Benjamin; Kinsland, Cynthia; Sanders, Jennie Mansell; Ealick, Steven E.; Begley, Tadhg P. (Cornell); (TAM)

    2012-06-26

    In Saccharomyces cerevisiae, thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.

  16. Prebiotic syntheses of purines and pyrimidines.

    Science.gov (United States)

    Basile, B; Lazcano, A; Oró, J

    1984-01-01

    The work done in many laboratories during the last two decades has confirmed that hydrogen cyanide and cyanoacetylene are the two major precursors for the prebiotic synthesis of purines and pyrimidines, respectively. Although several different pathways for the synthesis of purines have been described, they are all variations of the initial mechanism proposed by Oró and Kimball, where hydrogen cyanide leads first to the formation of a 4,5-di-substituted imidazole derivative, and then to the closing of the purine ring with a C1 compound. A number of experiments have shown that purines and pyrimidines can also be obtained from methane, ammonia (nitrogen), and water mixtures, provided an activating source of energy (radiation, electric discharges, etc.) is available. However, in this case the yields are lower by about two orders of magnitude because of the intermediate formation of hydrogen cyanide and cyanoacetylene. The latter two compounds have been found in interstellar space, Titan and other bodies of the solar system. They were probably present in the primordial parent bodies from the solar nebula in concentrations of 10(-2) to 10(-3) M as inferred from recent calculations by Miller and coworkers obtained for the Murchison meteorite. These concentrations should have been sufficient to generate relatively large amounts of purine and pyrimidine bases on the primitive Earth.

  17. Formation of trans-2-[4-(Dimethylamino)Styryl]-3-Ethyl-1,3-Benzothiazolium Perchlorate Dimers in the Presence of Sodium Polystyrene Sulfonate

    Science.gov (United States)

    Lavysh, A. V.; Maskevich, A. A.; Lugovskii, A. A.; Voropai, E. S.; Sulatskaya, A. I.; Kuznetsova, I. M.; Turoverov, K. K.

    2017-01-01

    The spectral properties of a novel thioflavin T derivative, trans-2-[4-(dimethylamino)styryl]-3-ethyl-1,3-benzothiazolium perchlorate (DMASEBT), were studied in aqueous solutions in the presence of sodium polystyrene sulfonate (SPS). It was shown that SPS either could interact with dye monomers or initiate the formation of non-fluorescent dye dimers depending on the concentration ratio of dye and polyelectrolyte. DMASEBT dimer formation in the presence of SPS produced a hypsochromic shift by 40 nm in the absorption spectrum and quenched fluorescence. A bathochromic shift of the absorption spectrum and an increase of the fluorescence intensity by an order of magnitude were observed if DMASEBT monomers interacted with SPS. Quantum-chemical analysis found that sandwich dimers (H-aggregates) were most stable. A comparison of DMASEBT spectra in the presence of SPS and amyloid fibrils showed that DMASEBT molecules were incorporated into amyloid fibrils as monomers. The spectral changes associated with this incorporation could not be explained by the formation of dye aggregates.

  18. A Search for Interstellar Pyrimidine

    CERN Document Server

    Kuan, Y J; Charnley, S B; Kisiel, Z; Ehrenfreund, P; Huang, H C; Kuan, Yi-Jehng; Yan, Chi-Hung; Charnley, Steven B.; Kisiel, Zbigniew; Ehrenfreund, Pascale; Huang, Hui-Chun

    2003-01-01

    We have searched three hot molecular cores for submillimeter emission from the nucleic acid building-block pyrimidine. We obtain upper limits to the total pyrimidine (beam-averaged) column densities towards Sgr B2(N), Orion KL and W51 e1/e2 of 1.7E+14 cm^{-2}, 2.4E+14 cm^{-2} and 3.4E+14 cm^{-2}, respectively. The associated upper limits to the pyrimidine fractional abundances lie in the range (0.3-3)E-10. Implications of this result for interstellar organic chemistry, and for the prospects of detecting nitrogen heterocycles in general, are briefly discussed.

  19. Crystal structure of dihydropyrimidinase from Pseudomonas aeruginosa PAO1: Insights into the molecular basis of formation of a dimer.

    Science.gov (United States)

    Tzeng, Ching-Ting; Huang, Yen-Hua; Huang, Cheng-Yang

    2016-09-23

    Dihydropyrimidinase, a tetrameric metalloenzyme, is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. In this paper, we report the crystal structure of dihydropyrimidinase from Pseudomonas aeruginosa PAO1 at 2.1 Å resolution. The structure of P. aeruginosa dihydropyrimidinase reveals a classic (β/α)8-barrel structure core embedding the catalytic dimetal center and a β-sandwich domain, which is commonly found in the architecture of dihydropyrimidinases. In contrast to all dihydropyrimidinases, P. aeruginosa dihydropyrimidinase forms a dimer, rather than a tetramer, both in the crystalline state and in the solution. Basing on sequence analysis and structural comparison of the C-terminal region and the dimer-dimer interface between P. aeruginosa dihydropyrimidinase and Thermus sp. dihydropyrimidinase, we propose a working model to explain why this enzyme cannot be a tetramer.

  20. Formation of a new copper(II) dimer through heterocyclic ligand ring opening reaction: Supramolecular features and magnetic properties

    Science.gov (United States)

    Gonçalves, Bruna Lisboa; Gervini, Vanessa Carratu; Flores, Alex Fabiani Claro; Junior, Jorge Luiz Pimentel; Bortoluzzi, Adailton João; Burrow, Robert Alan; Duarte, Rafael; da Silva, Robson Ricardo; Vicenti, Juliano Rosa de Menezes

    2017-01-01

    Two new compounds were synthesized and characterized in this work: the heterocycle (Z)-1-(4-(hydroxyimino)-3,5-dimethyl-1-(methylcarbamothioyl)-4,5-dihydro-1H-pyrazol-5-yl)-4-methylthiosemicarbazide and a copper(II) thiosemicarbazonato dimeric complex. Green prismatic single crystals of the dimer were obtained by the reaction of the heterocycle with copper(II) chloride dihydrate. Both compounds were essentially characterized by spectroscopic methods and X-ray diffraction crystallography. The crystal structures revealed molecules connected through supramolecular hydrogen bond interactions and copper(II) centers in a slightly distorted square-pyramidal environment. SQUID magnetometry performed for the dimer revealed both ferromagnetic and antiferromagnetic interactions in the studied complex, presenting a critical temperature of 19 K.

  1. Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus

    DEFF Research Database (Denmark)

    Lauritsen, Iben; Willemoës, Martin; Jensen, Kaj Frank;

    2011-01-01

    CTP synthase catalyzes the last committed step in de novo pyrimidine-nucleotide biosynthesis. Active CTP synthase is a tetrameric enzyme composed of a dimer of dimers. The tetramer is favoured in the presence of the substrate nucleotides ATP and UTP; when saturated with nucleotide, the tetramer c...

  2. Formation of a cyclic dimer containing two mirror image monomers in the solid state controlled by van der Waals forces.

    Science.gov (United States)

    Zhang, Zibin; Yu, Guocan; Han, Chengyou; Liu, Jiyong; Ding, Xia; Yu, Yihua; Huang, Feihe

    2011-09-16

    Two new copillar[5]arenes were prepared. They are arranged in two completely different motifs, a cyclic dimer containing two monomers with two different conformations that are mirror images of each other and linear supramolecular polymers in the solid state. Not only has it been shown that to form this kind of dimer is a unique feature associated with pillar[5]arene macrocycles but also it was demonstrated that weak van der Waals forces can be used to control the self-organization of monomers during their supramolecular polymerization process.

  3. Universality in bosonic dimer-dimer scattering

    Energy Technology Data Exchange (ETDEWEB)

    Deltuva, A. [Centro de Fisica Nuclear, Universidade de Lisboa, P-1649-003 Lisboa (Portugal)

    2011-08-15

    Bosonic dimer-dimer scattering is studied near the unitary limit using momentum-space equations for the four-particle transition operators. The impact of the Efimov effect on the dimer-dimer scattering observables is explored, and a number of universal relations is established with high accuracy. The rate for the creation of Efimov trimers via dimer-dimer collisions is calculated.

  4. Multiple spectroscopic and magnetic techniques show that chloroquine induces formation of the μ-oxo dimer of ferriprotoporphyrin IX.

    Science.gov (United States)

    Kuter, David; Benjamin, Stefan J; Egan, Timothy J

    2014-04-01

    Interaction of the antimalarial chloroquine (CQ) with ferriprotoporphyrin IX, Fe(III)PPIX, was investigated in aqueous solution (pH7.4) and as a precipitate from aqueous medium at pH5.0. In solution, spectrophotometric titrations indicated strong association (logKobs 13.3±0.2) and a Job plot gave a stoichiometry of 1:2 CQ:Fe(III)PPIX. UV-visible absorbance and magnetic circular dichroism spectra of the complex were compared to various Fe(III)PPIX species. Close similarity to the spectra of the μ-oxo dimer, μ-[Fe(III)PPIX]2O, was revealed. The induction of this species by CQ was confirmed by magnetic susceptibility measurements using the Evans NMR method. The observed low-magnetic moment (2.25±0.02 μB) could only be attributed to antiferromagnetically coupled Fe(III) centers. The value was comparable to that of μ-[Fe(III)PPIX]2O (2.0±0.1 μB). In the solid-state, mass spectrometry confirmed the presence of CQ in the complex. Dissolution of this solid in aqueous solution (pH7.4) resulted in a solution with a UV-visible spectrum consistent with the same 1:2 stoichiometry observed in the Job plot. Magnetic susceptibility measurements made on the solid using an Evans balance produced a magnetic moment (2.3±0.1 μB) consistent with that in solution. Diffusion coefficients of CQ and its complex with Fe(III)PPIX were measured in aqueous solution (3.3±0.3 and 0.6±0.2×10(-10) m(2)·s(-1), respectively). The latter was used in conjunction with an empirical relationship between diffusion coefficient and molar volume to estimate the degree of aggregation. The findings suggest the formation of a 2:4 CQ:Fe(III)PPIX complex in aqueous solution at pH7.4.

  5. Studies on the Effect of Sub-zero Temperatures on the Formation of Extremely Low Volatility Dimer Esters in Secondary Organic Aerosol from Alpha-Pinene

    Science.gov (United States)

    Kristensen, Kasper; Normann Jensen, Louise; Bilde, Merete

    2016-04-01

    The oxidation of volatile organic compounds (VOC) is considered a major source of secondary organic aerosols (SOA) in the atmosphere. Recently, extremely low volatility organic compounds, or ELVOC, formed from the oxidation of VOCs have been shown to play a crucial role in new particle formation (Ehn et al., 2014). In addition, higher molecular weight dimer esters originating from the oxidation of the biogenic VOC alpha-pinene have been observed in both laboratory-generated and ambient SOA (Kristensen et al., 2013). The low volatility of the dimer esters along with an observed rapid formation makes these high molecular weight compounds likely candidates involved in new particle formation from the oxidation of alpha-pinene. Furthermore, laboratory experiments show that the dimer esters only form in the presence of ozone, thus may be used as tracers for the ozone-initiated oxidation of alpha-pinene, and are therefore indicative of enhanced anthropogenic activities. In this work, we present the results of a series of oxidation experiments performed in the newly constructed cold-room smog chamber at Aarhus University. This unique and state-of-the-art Teflon chamber allows for atmospheric simulations of the oxidation VOCs and subsequent SOA formation at temperatures down to -16 °C. In this study, ozonolysis and photochemical oxidations of alpha-pinene are performed at temperatures ranging from +20 to -16 °C. Chemical characterization of the formed SOA is performed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The results show significant differences in the chemical composition related to the experiment temperature. In particularly, the concentration of the high molecular weight dimer esters showed to be highly affected by temperature. Interestingly, preliminary results show higher formation of dimer esters related to increased SOA formation rate, thus indicating that these particle-phase ELVOCs may be linked with new particle

  6. Using stable MutS dimers and tetramers to quantitatively analyze DNA mismatch recognition and sliding clamp formation

    NARCIS (Netherlands)

    M.K. Groothuizen; A. Fish (Alexander); M.V. Petoukhov (Maxim); A. Reumer (Annet); L. Manelyte (Laura); H.H.K. Winterwerp (Herrie); M.G. Marinus (Martin); J.H.G. Lebbink (Joyce); D.I. Svergun (Dmitri); P. Friedhoff (Peter); T.K. Sixma (Titia)

    2013-01-01

    textabstractThe process of DNA mismatch repair is initiated when MutS recognizes mismatched DNA bases and starts the repair cascade. The Escherichia coli MutS protein exists in an equilibrium between dimers and tetramers, which has compromised biophysical analysis. To uncouple these states, we have

  7. Molecular chirality and chiral capsule-type dimer formation of cyclic triamides via hydrogen-bonding interactions.

    Science.gov (United States)

    Fujimoto, Noriko; Matsumura, Mio; Azumaya, Isao; Nishiyama, Shizuka; Masu, Hyuma; Kagechika, Hiroyuki; Tanatani, Aya

    2012-05-18

    Chiral properties of bowl-shaped cyclic triamides bearing functional groups with hydrogen-bonding ability were examined. Chiral induction of cyclic triamide 3a was observed by addition of chiral amine in solution, and chiral separation was achieved by simple crystallization to afford chiral capsule-type dimer structure of 4a.

  8. Increased disulphide dimer formation of latent associated peptide fusions of TGF-β by addition of L-cystine.

    Science.gov (United States)

    Mullen, Lisa M; Adams, Gill; Chernajovsky, Yuti

    2012-10-31

    The development of novel protein therapeutics relies on the ability to express appreciable amounts of correctly folded recombinant proteins. Latent IFN-β is engineered using the latency-associated peptide (LAP) of transforming growth factor β1 (TGF-β1) to maintain IFN-β in a biologically inactive form until such time as it is released at sites of inflammation by matrix metalloproteinase activity (see Adams et al., 2003). CHO cells cultured in suspension were used for expression of latent IFN-β to allow medium scale transient transfection. However, the recombinant protein expressed in this system consisted of a mixture of properly linked disulphide dimers and monomers. The ratio of dimer:monomer produced could be significantly altered towards increased dimer production by the addition of L-cystine to the CHO culture medium. The total yield of latent IFN-β was increased by co-transfection of plasmid coding for the simian virus (SV) 40 large T antigen to the plasmid with the SV40 origin of replication expressing latent IFN-β DNA. These results provide valuable new insights for developing protocols to produce substantial quantities of latent cytokine dimers in CHO cells in suspension.

  9. Dimerization of VirD2 binding protein is essential for Agrobacterium induced tumor formation in plants.

    Directory of Open Access Journals (Sweden)

    Abhilash Padavannil

    2014-03-01

    Full Text Available The Type IV Secretion System (T4SS is the only bacterial secretion system known to translocate both DNA and protein substrates. The VirB/D4 system from Agrobacterium tumefaciens is a typical T4SS. It facilitates the bacteria to translocate the VirD2-T-DNA complex to the host cell cytoplasm. In addition to protein-DNA complexes, the VirB/D4 system is also involved in the translocation of several effector proteins, including VirE2, VirE3 and VirF into the host cell cytoplasm. These effector proteins aid in the proper integration of the translocated DNA into the host genome. The VirD2-binding protein (VBP is a key cytoplasmic protein that recruits the VirD2-T-DNA complex to the VirD4-coupling protein (VirD4 CP of the VirB/D4 T4SS apparatus. Here, we report the crystal structure and associated functional studies of the C-terminal domain of VBP. This domain mainly consists of α-helices, and the two monomers of the asymmetric unit form a tight dimer. The structural analysis of this domain confirms the presence of a HEPN (higher eukaryotes and prokaryotes nucleotide-binding fold. Biophysical studies show that VBP is a dimer in solution and that the HEPN domain is the dimerization domain. Based on structural and mutagenesis analyses, we show that substitution of key residues at the interface disrupts the dimerization of both the HEPN domain and full-length VBP. In addition, pull-down analyses show that only dimeric VBP can interact with VirD2 and VirD4 CP. Finally, we show that only Agrobacterium harboring dimeric full-length VBP can induce tumors in plants. This study sheds light on the structural basis of the substrate recruiting function of VBP in the T4SS pathway of A. tumefaciens and in other pathogenic bacteria employing similar systems.

  10. Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi-functional c-di-GMP regulator.

    Science.gov (United States)

    Phippen, Curtis William; Mikolajek, Halina; Schlaefli, Henry George; Keevil, Charles William; Webb, Jeremy Stephen; Tews, Ivo

    2014-12-20

    Diguanylate cyclases (DGC) and phosphodiesterases (PDE), respectively synthesise and hydrolyse the secondary messenger cyclic dimeric GMP (c-di-GMP), and both activities are often found in a single protein. Intracellular c-di-GMP levels in turn regulate bacterial motility, virulence and biofilm formation. We report the first structure of a tandem DGC-PDE fragment, in which the catalytic domains are shown to be active. Two phosphodiesterase states are distinguished by active site formation. The structures, in the presence or absence of c-di-GMP, suggest that dimerisation and binding pocket formation are linked, with dimerisation being required for catalytic activity. An understanding of PDE activation is important, as biofilm dispersal via c-di-GMP hydrolysis has therapeutic effects on chronic infections.

  11. Dual-color reporter switching system to discern dimer formations of G-protein-coupled receptors using Cre/loxP site-specific recombination in yeast.

    Science.gov (United States)

    Nakamura, Yasuyuki; Hashimoto, Takamichi; Ishii, Jun; Kondo, Akihiko

    2016-10-01

    G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that represent major molecular targets in pharmaceutical and medicinal fields. Many GPCRs have been shown to form not only homodimers, but also heterodimers that can confer large functional and physiological diversity and are therefore expected to offer new opportunities for the discovery of new drugs. Yeast is a useful host organism that can be used to investigate the interactions between eukaryotic protein pairs, as demonstrated by the yeast two-hybrid (Y2H) system. Previously, we established reporter gene assay systems to screen for GPCR dimer pairs based on the split-ubiquitin membrane Y2H (mY2H) system. However, conventional systems only induce reporter gene expressions from the OFF to ON states. In this study, we therefore designed a reporter switching system that can switch the expressions between two reporter genes (one from ON to OFF and the other from OFF to ON) in response to the Y2H readout. To invoke reporter switching, we took advantage of Cre/loxP site-specific recombination. Through optimization of Cre-mediated reporter gene recombination using the split-ubiquitin mY2H system, we built a dual-color reporter switching system to discern the formations of GPCR dimers. This system enabled monitoring of the formations of homodimers and heterodimers of human serotonin 1A receptor or β2 -adrenergic receptor as well as homodimers of the yeast endogenous pheromone receptor (Ste2p) in yeast cells. Our reporter switching system may be a useful tool for identifying potential molecular targets among GPCR dimers, and is also applicable to other reporter gene assay systems. Biotechnol. Bioeng. 2016;113: 2178-2190. © 2016 Wiley Periodicals, Inc.

  12. Pyrimidine as antiinflammatory agent: A review

    Directory of Open Access Journals (Sweden)

    Amir M

    2007-01-01

    Full Text Available Pyrimidine nucleus exhibited remarkable pharmacological activities. Literature indicates that compounds having pyrimidine nucleus have wide range of therapeutic uses that include antiinflammatory, antibacterial, anticancer, antiviral, antiHIV, antimalarial, antihypertensive, sedatives and hypnotics, anticonvulsant and antihistaminic. The present review provides a broad view of the antiinflammatory activity possessed by compounds having a pyrimidine nucleus.

  13. Interaction with the 5D3 monoclonal antibody is regulated by intramolecular rearrangements but not by covalent dimer formation of the human ABCG2 multidrug transporter

    DEFF Research Database (Denmark)

    Özvegy-Laczka, Csilla; Laczkó, Rozália; Hegedűs, Csilla;

    2008-01-01

    Human ABCG2 is a plasma membrane glycoprotein working as a homodimer or homo-oligomer. The protein plays an important role in the protection/detoxification of various tissues and may also be responsible for the multidrug-resistant phenotype of cancer cells. In our previous study we found that the 5......D3 monoclonal antibody shows a function-dependent reactivity to an extracellular epitope of the ABCG2 transporter. In the current experiments we have further characterized the 5D3-ABCG2 interaction. The effect of chemical cross-linking and the modulation of extracellular S-S bridges...... on the transporter function and 5D3 reactivity of ABCG2 were investigated in depth. We found that several protein cross-linkers greatly increased 5D3 labeling in ABCG2 expressing HEK cells; however, there was no correlation between covalent dimer formation, the inhibition of transport activity, and the increase in 5...

  14. Influence of exogenous silicon on UV-B radiation-induced cyclobutane pyrimidine dimmers in soybean leaves and its alleviation mechanism.

    Science.gov (United States)

    Chen, Jiana; Zhang, Mingcai; Eneji, A Egrinya; Li, Jianmin

    2016-06-01

    The DNA is particularly sensitive to UV-B radiation and can readily be damaged by UV-B stress, resulting to the formation of photoproducts like cyclobutane pyrimidine dimers (CPDs). Silicon has multifarious benefits to plants, especially under biotic and abiotic stress. In this study, we used soybean seedlings to determine whether silicon could alleviate damage to DNA caused by UV-B stress. Silicon significantly reduced the accumulation of CPDs, lessening the damage of UV-B stress to the seedlings by the following three mechanisms: (1) increasing the concentration of UV-B absorbing compounds to reduce damage; (2) strengthening the antioxidant capacity of plants represented by higher levels of non-enzymatic antioxidants and (3) increasing the photolyase gene expression, thus accelerating photorepair.

  15. Biofilm formation and antibiotic production in Ruegeria mobilis are influenced by intracellular concentrations of cyclic dimeric guanosinmonophosphate

    DEFF Research Database (Denmark)

    D'Alvise, Paul; Magdenoska, Olivera; Melchiorsen, Jette

    2014-01-01

    formation and production of the potent antibiotic tropodithietic acid (TDA). An introduced phosphodiesterase gene decreased c-di-GMP and reduced biofilm formation and TDA production. tdaC, a key gene for TDA biosynthesis, was expressed only in attached or biofilm-forming cells, and expression was induced...

  16. The pyrimidine operon pyrRPB-carA from Lactococcus lactis

    DEFF Research Database (Denmark)

    Martinussen, Jan; Schallert, J.; Andersen, Birgit;

    2001-01-01

    The four genes pyrR, pyrP, pyrB, and carA were found to constitute an operon in Lactococcus lactis subsp, lactis MG1363. The functions of the different genes were established by mutational analysis. The first gene in the operon is the pyrimidine regulatory gene, pyrR, which is responsible...... for the regulation of the expression of the pyrimidine biosynthetic genes leading to UMP formation. The second gene encodes a membrane-bound high-affinity uracil permease, required for utilization of exogenous uracil. The last two genes in the operon, pyrB and carA, encode pyrimidine biosynthetic enzymes; aspartate....... The expression of the pyrimidine biosynthetic genes including the pyrRPB-carA operon is subject to control at the transcriptional level, most probably by an attenuator mechanism in which PyrR acts as the regulatory protein....

  17. Thermodynamics of the formation of sulfuric acid dimers in the binary (H2SO4-H2O and ternary (H2SO4-H2O-NH3 system

    Directory of Open Access Journals (Sweden)

    A. Kürten

    2015-05-01

    Full Text Available Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF. Both the binary (H2SO4-H2O system, and the ternary system involving ammonia (H2SO4-H2O-NH3 may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a Chemical Ionization Mass Spectrometer (CIMS. From these measurements dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4 • NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248 K. We estimate the thermodynamic properties (dH and dS of the H2SO4 • NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF mass spectrometry.

  18. Tracking Rh Atoms in Zeolite HY: First Steps of Metal Cluster Formation and Influence of Metal Nuclearity on Catalysis of Ethylene Hydrogenation and Ethylene Dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dong; Xu, Pinghong; Browning, Nigel D.; Gates, Bruce C.

    2016-07-07

    The initial steps of rhodium cluster formation from zeolite-supported mononuclear Rh(C2H4)2 complexes in H2 at 373 K and 1 bar were investigated by infrared and extended X-ray absorption fine structure spectroscopies and scanning transmission electron microscopy (STEM). The data show that ethylene ligands on the rhodium react with H2 to give supported rhodium hydrides and trigger the formation of rhodium clusters. STEM provided the first images of the smallest rhodium clusters (Rh2) and their further conversion into larger clusters. The samples were investigated in a plug-flow reactor as catalysts for the conversion of ethylene + H2 in a molar ratio of 4:1 at 1 bar and 298 K, with the results showing how the changes in catalyst structure affect the activity and selectivity; the rhodium clusters are more active for hydrogenation of ethylene than the single-site complexes, which are more selective for dimerization of ethylene to give butenes

  19. Interruption of electronically excited Xe dimer formation by the photoassociation of Xe(6s[3/2]2)-Xe(5p(6) (1)S0) thermal collision pairs.

    Science.gov (United States)

    Galvin, T C; Wagner, C J; Eden, J G

    2016-06-28

    The diatomic collisional intermediate responsible for the formation of an electronically excited molecule by teratomic recombination has been observed in both the spectral and temporal domains by laser spectroscopy. We report experiments demonstrating thermal Xe(6s[3/2]2)-Xe(5p(6) (1)S0) atomic collision pairs to be the immediate precursor to the formation of Xe2 (∗)(a(3)Σu (+),A(1)Σu (+)) by the three body process: Xe(∗)(6s) + 2Xe ⟶ Xe2 (∗) + Xe, where the asterisk denotes an excited electronic state. Photoassociating Xe(6s)-Xe atomic pairs by free ⟵ free transitions of the collision complex interrupts the production of the electronically excited Xe dimer, thereby suppressing Xe2 spontaneous emission in the vacuum ultraviolet (VUV, λ ∼ 172 nm, A(1)Σu (+)→X(1)Σg (+)). Intercepting Xe(6s)-Xe pairs before the complex is stabilized by the arrival of the third atom in the teratomic collision process selectively depletes the pair population in a specific Franck-Condon region determined by the probe laser wavelength (λ). Measurements of the variation of VUV emission suppression with λ provide a spectral signature of the [Xe(6s[3/2]2) - Xe((1)S0)](∗) complex and map the probe laser wavelength onto the thermal energy (ϵ″) of the incoming collision pairs.

  20. Interruption of electronically excited Xe dimer formation by the photoassociation of Xe(6s[3/2]2)-Xe(5p6 1S0) thermal collision pairs

    Science.gov (United States)

    Galvin, T. C.; Wagner, C. J.; Eden, J. G.

    2016-06-01

    The diatomic collisional intermediate responsible for the formation of an electronically excited molecule by teratomic recombination has been observed in both the spectral and temporal domains by laser spectroscopy. We report experiments demonstrating thermal Xe(6s[3/2]2)-Xe(5p6 1S0) atomic collision pairs to be the immediate precursor to the formation of Xe 2∗ ( a 3 Σu + , A 1 Σu +) by the three body process: Xe∗(6s) + 2Xe ⟶ Xe 2∗ + Xe, where the asterisk denotes an excited electronic state. Photoassociating Xe(6s)-Xe atomic pairs by free ⟵ free transitions of the collision complex interrupts the production of the electronically excited Xe dimer, thereby suppressing Xe2 spontaneous emission in the vacuum ultraviolet (VUV, λ ˜ 172 nm, A 1 Σu + → X 1 Σg +). Intercepting Xe(6s)-Xe pairs before the complex is stabilized by the arrival of the third atom in the teratomic collision process selectively depletes the pair population in a specific Franck-Condon region determined by the probe laser wavelength (λ). Measurements of the variation of VUV emission suppression with λ provide a spectral signature of the [Xe(6s[3/2]2) - Xe(1S0)]∗ complex and map the probe laser wavelength onto the thermal energy (ɛ″) of the incoming collision pairs.

  1. Dimerization of Human Growth Hormone by Zinc

    Science.gov (United States)

    Cunningham, Brian C.; Mulkerrin, Michael G.; Wells, James A.

    1991-08-01

    Size-exclusion chromatography and sedimentation equilibrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn2+-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn2+-hGH dimeric complex may be important for storage of hGH in secretory granules.

  2. submitter Thermodynamics of the formation of sulfuric acid dimers in the binary (H2SO4–H2O) and ternary (H2SO4–H2O–NH3) system

    CERN Document Server

    Kürten, A; Rondo, L; Bianchi, F; Duplissy, J; Jokinen, T; Junninen, H; Sarnela, N; Schobesberger, S; Simon, M; Sipilä, M; Almeida, J; Amorim, A; Dommen, J; Donahue, N M; Dunne, E M; Flagan, R C; Franchin, A; Kirkby, J; Kupc, A; Makhmutov, V; Petäjä, T; Praplan, A P; Riccobono, F; Steiner, G; Tomé, A; Tsagkogeorgas, G; Wagner, P E; Wimmer, D; Baltensperger, U; Kulmala, M; Worsnop, D R; Curtius, J

    2015-01-01

    Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary $(H_2SO_4–H_2O)$ system and the ternary system involving ammonia $(H_2SO_4–H_2O–NH_3)$ may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a chemical ionization mass spectrometer (CIMS). From these measurements, dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary sys...

  3. Ultraviolet irradiation of DNA complexed with. alpha. /. beta. -type small, acid-soluble proteins from spores of Bacillus or Clostridium species makes spore photoproduct but not thymine dimers

    Energy Technology Data Exchange (ETDEWEB)

    Nicholson, W.L.; Setlow, B.; Setlow, P. (Univ. of Connecticut Health Center, Farmington (United States))

    1991-10-01

    UV irradiation of complexes of DNA and an {alpha}/{beta}-type small, acid-soluble protein (SASP) from Bacillus subtilis spores gave decreasing amounts of pyrimidine dimers and increasing amounts of spore photoproduct as the SASP/DNA ratio was increased. The yields of pyrimidine dimers and spore photoproduct were < 0.2% and 8% of total thymine, respectively, when DNA saturated with SASP was irradiated at 254 nm with 30 kJ/m{sup 2}; in the absence of SASP the yields were reversed - 4.5% and 0.3%, respectively. Complexes of DNA with {alpha}/{beta}-type SASP from Bacillus cereus, Bacillus megaterium, or Clostridium bifermentans spores also gave spore photoproduct upon UV irradiation. However, incubation of these SASPs with DNA under conditions preventing complex formation or use of mutant SASPs that do not form complexes did not affect the photoproducts formed in vitro. These results suggest that the UV photochemistry of bacterial spore DNA in vivo is due to the binding of {alpha}/{beta}-type SASP, a binding that is known to cause a change in DNA conformation in vitro from the B form to the A form. The yields of spore photoproduct in vitro were significantly lower than in vivo, perhaps because of the presence of substances other than SASP in spores. It is suggested that as these factors diffuse out in the first minutes of spore germination, spore photoproduct yields become similar to those observed for irradiation of SASP/DNA complexes in vitro.

  4. Dimerization of norbornene on zeolite catalysts

    Institute of Scientific and Technical Information of China (English)

    N. G. Grigor’eva; S. V. Bubennov; L. M. Khalilov; B. I. Kutepov

    2015-01-01

    The high activity and selectivity of H‐Beta and H‐ZSM‐12 zeolites in the dimerization of norbornene was established. The norbornene conversion reached 100%in chlorinated paraffin and argon gas medium, with a selectivity of dimer formation of 88%–98%. Four stereo‐isomers of the bis‐2,2’‐norbornylidene structure were identified in the dimer fraction, with the (Z)‐anti‐bis‐2,2’‐norbornylidene prevailing over the others.

  5. Role of Human DNA Polymerase kappa in Extension Opposite from a cis-syn Thymine Dimer

    Energy Technology Data Exchange (ETDEWEB)

    R Vasquez-Del Carpio; T Silverstein; S Lone; R Johnson; L Prakash; S Prakash; A Aggarwal

    2011-12-31

    Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase {Kappa} (Pol{Kappa}), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3'T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3'T of the dimer by another DNA polymerase. We present here the structure of human Pol{Kappa} in the act of inserting a nucleotide opposite the 5'T of the cis-syn T-T dimer. The structure reveals a constrained active-site cleft that is unable to accommodate the 3'T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5'T via Watson-Crick base pairing, in accord with a proposed role for Pol{Kappa} in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.

  6. Potassium Hexacyanoferrate (III-Catalyzed Dimerization of Hydroxystilbene: Biomimetic Synthesis of Indane Stilbene Dimers

    Directory of Open Access Journals (Sweden)

    Jing-Shan Xie

    2015-12-01

    Full Text Available Using potassium hexacyanoferrate (III–sodium acetate as oxidant, the oxidative coupling reaction of isorhapontigenin and resveratrol in aqueous acetone resulted in the isolation of three new indane dimers 4, 6, and 7, together with six known stilbene dimers. Indane dimer 5 was obtained for the first time by direct transformation from isorhapontigenin. The structures and relative configurations of the dimers were elucidated using spectral analysis, and their possible formation mechanisms were discussed. The results indicate that this reaction could be used as a convenient method for the semi-synthesis of indane dimers because of the mild conditions and simple reaction products.

  7. Polyurethane Foams with Pyrimidine Rings

    Directory of Open Access Journals (Sweden)

    Kania Ewelina

    2014-09-01

    Full Text Available Oligoetherols based on pyrimidine ring were obtained upon reaction of barbituric acid with glycidol and alkylene carbonates. These oligoetherols were then used to obtain polyurethane foams in the reaction of oligoetherols with isocyanates and water. The protocol of foam synthesis was optimized by the choice of proper kind of oligoetherol and synthetic composition. The thermal resistance was studied by dynamic and static methods with concomitant monitoring of compressive strength. The polyurethane foams have similar physical properties as the classic ones except their enhanced thermal resistance. They stand long-time heating even at 200°C. Moreover thermal exposition of foams results generally in increase of their compressive strength.

  8. Structural Basis for Dimer Formation of Human Condensin Structural Maintenance of Chromosome Proteins and Its Implications for Single-stranded DNA Recognition.

    Science.gov (United States)

    Uchiyama, Susumu; Kawahara, Kazuki; Hosokawa, Yuki; Fukakusa, Shunsuke; Oki, Hiroya; Nakamura, Shota; Kojima, Yukiko; Noda, Masanori; Takino, Rie; Miyahara, Yuya; Maruno, Takahiro; Kobayashi, Yuji; Ohkubo, Tadayasu; Fukui, Kiichi

    2015-12-01

    Eukaryotic structural maintenance of chromosome proteins (SMC) are major components of cohesin and condensins that regulate chromosome structure and dynamics during cell cycle. We here determine the crystal structure of human condensin SMC hinge heterodimer with ~30 residues of coiled coils. The structure, in conjunction with the hydrogen exchange mass spectrometry analyses, revealed the structural basis for the specific heterodimer formation of eukaryotic SMC and that the coiled coils from two different hinges protrude in the same direction, providing a unique binding surface conducive for binding to single-stranded DNA. The characteristic hydrogen exchange profiles of peptides constituted regions especially across the hinge-hinge dimerization interface, further suggesting the structural alterations upon single-stranded DNA binding and the presence of a half-opened state of hinge heterodimer. This structural change potentially relates to the DNA loading mechanism of SMC, in which the hinge domain functions as an entrance gate as previously proposed for cohesin. Our results, however, indicated that this is not the case for condensins based on the fact that the coiled coils are still interacting with each other, even when DNA binding induces structural changes in the hinge region, suggesting the functional differences of SMC hinge domain between condensins and cohesin in DNA recognition.

  9. The catalytic effect of water, water dimers and water trimers on H2S + (3)O2 formation by the HO2 + HS reaction under tropospheric conditions.

    Science.gov (United States)

    Zhang, Tianlei; Yang, Chen; Feng, Xukai; Kang, Jiaxin; Song, Liang; Lu, Yousong; Wang, Zhiyin; Xu, Qiong; Wang, Wenliang; Wang, Zhuqing

    2016-06-29

    In this article, the reaction mechanisms of H2S + (3)O2 formation by the HO2 + HS reaction without and with catalyst X (X = H2O, (H2O)2 and (H2O)3) have been investigated theoretically at the CCSD(T)/6-311++G(3df,2pd)//B3LYP/6-311+G(2df,2p) level of theory, coupled with rate constant calculations by using conventional transition state theory. Our results show that in the presence of catalyst X (X = H2O, (H2O)2 and (H2O)3) into the channel of H2S + (3)O2 formation, the reactions between the SH radical and HO2(H2O)n (n = 1-3) complexes are more favorable than the corresponding reactions of the HO2 radical with HS(H2O)n (n = 1-3) complexes due to the lower barrier of the former reactions and the higher concentrations of HO2(H2O)n (n = 1-3) complexes. Meanwhile, the catalytic effect of water, water dimers and water trimers is mainly taken from the contribution of a single water vapor molecule, since the total effective rate constant of HO2H2O + HS and H2OHO2 + HS reactions was, respectively, larger by 7-9 and 9-12 orders of magnitude than that of SH + HO2(H2O)2 and SH + HO2(H2O)3 reactions. Besides, the enhancement factor of water vapor is only 0.37% at 240 K, while at high temperatures, such as 425 K, the positive water vapor effect is enhanced up to 38.00%, indicating that at high temperatures the positive water effect is obvious under atmospheric conditions. Overall, these results show how water and water clusters catalyze the gas phase reactions under atmospheric conditions.

  10. Universal four-Boson states in ultracold molecular gases: resonant effects in dimer-dimer collisions.

    Science.gov (United States)

    D'Incao, J P; von Stecher, J; Greene, Chris H

    2009-07-17

    We study the manifestations of universal four-body physics in ultracold dimer-dimer collisions. We show that resonant features associated with three-body Efimov physics and dimer-dimer scattering lengths are universally related. The emergence of universal four-boson states allows for the tunability of the dimer-dimer interaction, thus enabling the future study of ultracold molecular gases with both attractive and repulsive interactions. Moreover, our study of the interconversion between dimers and Efimov trimers shows that B2+B2-->B3+B rearrangement reactions can provide an efficient trimer formation mechanism. Our analysis of the temperature dependence of this reaction provides an interpretation of the available experimental data and sheds light on the possible experimental realization of rearrangement processes in ultracold gases.

  11. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.;

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

  12. Homogeneous gas-phase formation of polychlorinated naphthalene from dimerization of 4-chlorophenoxy radicals and cross-condensation of phenoxy radical with 4-chlorophenoxy radical: Mechanism and kinetics study

    Science.gov (United States)

    Xu, Fei; Zhang, Ruiming; Li, Yunfeng; Zhang, Qingzhu

    2015-10-01

    A direct density functional theory (DFT) calculation was performed for the formation of polychlorinated naphthalenes (PCNs) from dimerization of 4-chlorophenoxy radicals (4-CPRs) and cross-condensation of phenoxy radical (PhR) with 4-CPR, respectively. Several energetically feasible formation routes were proposed. The rate constants were computed by the canonical variational transition-state theory (CVT) with the small curvature tunneling (SCT) contribution over temperature range of 600-1200 K. This study shows that PCN productions from the dimerization of 4-CPRs just contain DCNs. All the monochlorinated naphthalene (MCN) detected in the experiment from 4-chlorophenol (4-CP) as precursor are formed form the cross-condensation of PhR with 4-CPR.

  13. Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

    Directory of Open Access Journals (Sweden)

    Marcel Mirel Popa

    2015-06-01

    Full Text Available The three possible structural isomers of 4-(pyridylpyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridylpyrimidine and 4-(4-pyridylpyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridylpyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridylpyrimidine and 4-(4-pyridylpyrimidine, are also reported.

  14. Identification and characterization of intermediates in the formation of the cyclobutadiene linked dimeric cobalt sandwich compound [(5-RCp)Co(4-C4Ph3)]2 [R = H, CH3C(O)O

    Indian Academy of Sciences (India)

    Nem Singh; Anil J Elias

    2011-11-01

    The synthesis of novel cyclobutadiene linked dimers of [5-RCp]Co(4-C4Ph4) was reported recently from a three-component reaction of 1,4-diphenylbutadiyne, diphenylacetylene and [5-RCp]Co(PPh3)2 [R = H or MeOC(O)]. The chiral bis oxazoline derivative of this dimer was found to form cobalt oxazolinyl palladacycles which were excellent chiral catalysts for the Overman-Claisen rearrangement of trichloroacetimidates, similar to the well-known COP catalysts. In this paper, we report reactions carried out for identifying the intermediates in the formation of the dimeric sandwich compound {[5-MeOC(O)Cp]Co(4-C4Ph3)}2 (1). On varying the stoichiometric ratio of the reactants of the three component reaction, two new cobalt sandwich compounds [5-MeOC(O)Cp]Co[4-C4Ph3(C≡CPh)] (2) and [5-MeOC(O)Cp]Co[4-C4-Ph2(C≡CPh)2] (3) were found to form as viscous oily liquids. The identity of 2 was ascertained by oxidizing its alkyne moiety to yield crystalline [5-MeOC(O)Cp]Co{4-C4Ph3[C(O)-C(O)Ph]} (4) which was structurally characterized. Further, the role of phenylethynyl derived monomeric sandwich compound 2 as a precursor to the dimeric compound 1 was established by reacting 2 with diphenylacetylene and CpCo(COD) which yielded the first example of an unsymmetrical cyclobutadiene linked dimeric cobalt sandwich compound {5-[MeOC(O)Cp]Co(4-C4Ph3)}[(5-Cp)Co(4-C4Ph3)] (5) which was also structurally characterized.

  15. Neutron scattering in dimers

    DEFF Research Database (Denmark)

    Gudel, H. U.; Furrer, A.; Kjems, Jørgen

    1986-01-01

    Insulating compounds containing dimers of transition metal and rare earth ions have been studied by inelastic neutron scattering (INS). Energy splittings can be directly determined, and the corresponding parameters are easily extracted from the experimental data. The intensities of dimer excitati......Insulating compounds containing dimers of transition metal and rare earth ions have been studied by inelastic neutron scattering (INS). Energy splittings can be directly determined, and the corresponding parameters are easily extracted from the experimental data. The intensities of dimer...

  16. N-(Pyrimidin-2-ylaniline

    Directory of Open Access Journals (Sweden)

    Edura Badaruddin

    2009-04-01

    Full Text Available There are two molecules in the asymmetric unit of the title compound, C10H9N3, with inter-ring dihedral angles of 31.1 (1 and 35.3 (1°. The bridging C—N—C bond angles are 128.2 (1 and 129.1 (1°. In the crystal, the two independent molecules are linked into a dimer by two N—H...N hydrogen bonds.

  17. Nucleobases and other Prebiotic Species from the Ultraviolet Irradiation of Pyrimidine in Astrophysical Ices

    Science.gov (United States)

    Sandford, S. A.; Nuevo, M.; Materese, C. K.; Milam, S. N.

    2012-01-01

    Nucleobases are N-heterocycles that are the informational subunits of DNA and RNA, and are divided into two families: pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in meteorites and their extraterrestrial origin confirmed by isotope measurement. Although no Nheterocycles have ever been observed in the ISM, the positions of the 6.2-m interstellar emission features suggest a population of such molecules is likely to be present. In this work we study the formation of pyrimidine-based molecules, including nucleobases, as well as other species of prebiotic interest, from the ultraviolet (UV) irradiation of pyrimidine in combinations of H2O, NH3, CH3OH, and CH4 ices at low temperature, in order to simulate the astrophysical conditions under which prebiotic species may be formed in the interstellar medium and icy bodies of the Solar System. Experimental: Gas mixtures are prepared in a glass mixing line (background pressure approx. 10(exp -6)-10(exp -5) mbar). Relative proportions between mixture components are determined by their partial pressures. Gas mixtures are then deposited on an aluminum foil attached to a cold finger (15-20 K) and simultaneously irradiated with an H2 lamp emitting UV photons (Lyman and a continuum at approx.160 nm). After irradiation samples are warmed to room temperature, at which time the remaining residues are recovered to be analyzed with liquid and gas chromatographies. Results: These experiments showed that the UV irradiation of pyrimidine mixed in these ices at low temperature leads to the formation of several photoproducts derived from pyrimidine, including the nucleobases uracil and cytosine, as well as their precursors 4(3H)-pyrimidone and 4-aminopyrimidine (Fig. 1). Theoretical quantum calculations on the formation of 4(3H)-pyrimidone and uracil from the irradiation of pyrimidine in pure H2O ices are in agreement with their experimental formation pathways. In

  18. Inwerking van stikstofhoudende nucleofielen op enige 15N-gemerkte pyrimidine- en chinazolinederivaten

    NARCIS (Netherlands)

    Kroon, A.P.

    1974-01-01

    In this thesis an investigation is described on the mechanism of aminations of pyrimidine- and quinazoline derivatives with nitrogen containing bases.In the introduction a survey is given of investigations, reported in the literature, concerning σ-complex formation on azahetarenes and their derivati

  19. Nucleobases and Other Prebiotic Species from the UV Irradiation of Pyrimidine in Astrophysical Ices

    Science.gov (United States)

    Sandford, Scott; Materese, Christopher; Nuevo, Michel

    2012-01-01

    Nucleobases are aromatic N-heterocycles that constitute the informational subunits of DNA and RNA and are divided into two families: pyrimidine bases (uracil, cytosine, and thymine) and purine bases (adenine and guanine). Nucleobases have been detected in meteorites and their extraterrestrial origin confirmed by isotope measurement. Although no N-heterocycles have been individually identified in the ISM, the 6.2-micron interstellar emission feature seen towards many astronomical objects suggests a population of such molecules is likely present. We report on a study of the formation of pyrimidine-based molecules, including nucleobases and other species of prebiotic interest, from the ultraviolet (UV) irradiation of pyrimidine in low temperature ices containing H2O, NH3, C3OH, and CH4, to simulate the astrophysical conditions under which prebiotic species may be formed in the Solar System.

  20. Formation of the productive ATP-Mg2+-bound dimer of GlcV, an ABC-ATPase from Sulfolobus solfataricus

    NARCIS (Netherlands)

    Verdon, G; Albers, SV; van Oosterwijk, N; Dijkstra, BW; Driessen, AJM; Thunnissen, AMWH; Dijkstra, Bauke W.

    2003-01-01

    The ABC-ATPase GlcV from Sulfolobus solfataricus energizes an ABC transporter mediating glucose uptake. In ABC transporters, two ABC-ATPases are believed to form a head-to-tail dimer, with both monomers contributing conserved residues to each of the two productive active sites. In contrast, isolated

  1. Reversible dimer formation and stability of the anti-tumour single-chain Fv antibody MFE-23 by neutron scattering, analytical ultracentrifugation, and NMR and FT-IR spectroscopy.

    Science.gov (United States)

    Lee, Yie Chia; Boehm, Mark K; Chester, Kerry A; Begent, Richard H J; Perkins, Stephen J

    2002-06-28

    seven other scFv molecules have shown that, while the contact residues for symmetric back-to-back dimer formation in MFE-23 are not fully conserved, in principle, back-to-back contacts can be formed in these too. This offers possibilities for the creation of other forms of scFv molecules.

  2. Construction of a ferritin dimer by breaking its symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, B; Uenuma, M; Uraoka, Y; Yamashita, I [Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

    2010-11-05

    Ferritin has a mono-dispersed structure and biomineralization properties that allow it to form various kinds of nanoparticles and play an important role in modern nanotechnology. Independent nanoparticles synthesized in ferritin are valuable, but moreover a pair of nanoparticles can bring new properties different from those of the independent nanoparticles. In this study, by breaking ferritin's symmetry, we successfully produced ferritin dimers which provide real protein frameworks for nanoparticle dimer formation. Identical nickel hydro-oxide nanoparticle dimers were produced by simply biomineralizing ferritin dimers. The method presented here can produce multi-functional ferritin dimers with different kinds of nanoparticles.

  3. Structure of cyanase reveals that a novel dimeric and decameric arrangement of subunits is required for formation of the enzyme active site.

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, M. A.; Otwinowski, Z.; Perrakis, A.; Anderson, P. M.; Joachimiak, A.; Biosciences Division; Univ. of Texas; European Molecular Biology Lab.; Univ. of Minnesota; Northwestern Univ.

    2000-01-01

    Cyanase is an enzyme found in bacteria and plants that catalyzes the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide. In Escherichia coli, cyanase is induced from the cyn operon in response to extracellular cyanate. The enzyme is functionally active as a homodecamer of 17 kDa subunits, and displays half-site binding of substrates or substrate analogs. The enzyme shows no significant amino acid sequence homology with other proteins. We have determined the crystal structure of cyanase at 1.65 {angstrom} resolution using the multiwavelength anomalous diffraction (MAD) method. Cyanase crystals are triclinic and contain one homodecamer in the asymmetric unit. Selenomethionine-labeled protein offers 40 selenium atoms for use in phasing. Structures of cyanase with bound chloride or oxalate anions, inhibitors of the enzyme, allowed identification of the active site. The cyanase monomer is composed of two domains. The N-terminal domain shows structural similarity to the DNA-binding {alpha}-helix bundle motif. The C-terminal domain has an 'open fold' with no structural homology to other proteins. The subunits of cyanase are arranged in a novel manner both at the dimer and decamer level. The dimer structure reveals the C-terminal domains to be intertwined, and the decamer is formed by a pentamer of these dimers. The active site of the enzyme is located between dimers and is comprised of residues from four adjacent subunits of the homodecamer. The structural data allow a conceivable reaction mechanism to be proposed.

  4. Liquid crystal dimers

    CERN Document Server

    Kumar Pal, Santanu

    2017-01-01

    This book covers in-depth discussion of design principles, synthesis and thermal behavior of all types of liquid crystal (LC) dimers. The text presents recent advances in the field of LC dimers consisting of different mesogenic units such as calamitic, discotic and bent-core molecules. It starts with a chapter on the introduction of liquid crystal dimers, including their odd-even behavior, basic classification of dimers and common mesophases in dimers. The text shows how the molecular architectures are being used to develop new materials to study a range of interesting phenomena such as the biaxial nematic phase containing rod-like and disc-like mesogenic units. Finally, the text presents perspectives related to technological relevance of these dimers such as dopants in LC display mixtures exhibiting faster relaxation time, strong flexoelectric coupling and others to effect control over the properties of these materials.

  5. Salt bridges regulate both dimer formation and monomeric flexibility in HdeB and may have a role in periplasmic chaperone function.

    Science.gov (United States)

    Wang, Wenjian; Rasmussen, Tim; Harding, Amanda J; Booth, Nuala A; Booth, Ian R; Naismith, James H

    2012-01-20

    Escherichia coli and Gram-negative bacteria that live in the human gut must be able to tolerate rapid and large changes in environmental pH. Low pH irreversibly denatures and precipitates many bacterial proteins. While cytoplasmic proteins are well buffered against such swings, periplasmic proteins are not. Instead, it appears that some bacteria utilize chaperone proteins that stabilize periplasmic proteins, preventing their precipitation. Two highly expressed and related proteins, HdeA and HdeB, have been identified as acid-activated chaperones. The structure of HdeA is known and a mechanism for activation has been proposed. In this model, dimeric HdeA dissociates at low pH, and the exposed dimeric interface binds exposed hydrophobic surfaces of acid-denatured proteins, preventing their irreversible aggregation. We now report the structure and biophysical characterization of the HdeB protein. The monomer of HdeB shares a similar structure with HdeA, but its dimeric interface is different in composition and spatial location. We have used fluorescence to study the behavior of HdeB as pH is lowered, and like HdeA, it dissociates to monomers. We have identified one of the key intersubunit interactions that controls pH-induced monomerization. Our analysis identifies a structural interaction within the HdeB monomer that is disrupted as pH is lowered, leading to enhanced structural flexibility.

  6. Salt Bridges Regulate Both Dimer Formation and Monomeric Flexibility in HdeB and May Have a Role in Periplasmic Chaperone Function

    Science.gov (United States)

    Wang, Wenjian; Rasmussen, Tim; Harding, Amanda J.; Booth, Nuala A.; Booth, Ian R.; Naismith, James H.

    2012-01-01

    Escherichia coli and Gram-negative bacteria that live in the human gut must be able to tolerate rapid and large changes in environmental pH. Low pH irreversibly denatures and precipitates many bacterial proteins. While cytoplasmic proteins are well buffered against such swings, periplasmic proteins are not. Instead, it appears that some bacteria utilize chaperone proteins that stabilize periplasmic proteins, preventing their precipitation. Two highly expressed and related proteins, HdeA and HdeB, have been identified as acid-activated chaperones. The structure of HdeA is known and a mechanism for activation has been proposed. In this model, dimeric HdeA dissociates at low pH, and the exposed dimeric interface binds exposed hydrophobic surfaces of acid-denatured proteins, preventing their irreversible aggregation. We now report the structure and biophysical characterization of the HdeB protein. The monomer of HdeB shares a similar structure with HdeA, but its dimeric interface is different in composition and spatial location. We have used fluorescence to study the behavior of HdeB as pH is lowered, and like HdeA, it dissociates to monomers. We have identified one of the key intersubunit interactions that controls pH-induced monomerization. Our analysis identifies a structural interaction within the HdeB monomer that is disrupted as pH is lowered, leading to enhanced structural flexibility. PMID:22138344

  7. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  8. Enzymology of Pyrimidine Metabolism and Neurodegeneration.

    Science.gov (United States)

    Vincenzetti, Silvia; Polzonetti, Valeria; Micozzi, Daniela; Pucciarelli, Stefania

    2016-01-01

    It is well known that disorders of pyrimidine pathways may lead to neurological, hematological, immunological diseases, renal impairments, and association with malignancies. Nucleotide homeostasis depends on the three stages of pyrimidine metabolism: de novo synthesis, catabolism and recycling of these metabolites. Cytidine and uridine, in addition to be used as substrates for pyrimidine nucleotide salvaging, also act as the precursors of cytidine triphosphate used in the biosynthetic pathway of both brain's phosphatidylcholine and phosphatidylethanolamine via the Kennedy cycle. The synthesis in the brain of phosphatidylcholine and other membrane phosphatides can utilize, in addition to glucose, three compounds present in the blood stream: choline, uridine, and a polyunsaturated fatty acids like docosahexaenoic acid. Some authors, using rat models, found that oral administration of two phospholipid precursors such as uridine and omega-3 fatty acids, along with choline from the diet, can increase the amount of synaptic membrane generated by surviving striatal neurons in rats with induced Parkinson's disease. Other authors found that in hypertensive rat fed with uridine and choline, cognitive deficit resulted improved. Uridine has also been recently considered as a neuroactive molecule, because of its involvement in important neurological functions by improving memory, sleep disorders, anti-epileptic effects, as well as neuronal plasticity. Cytidine and uridine are uptaken by the brain via specific receptors and successively salvaged to the corresponding nucleotides. The present review is devoted to the enzymology of pyrimidine pathways whose importance has attracted the attention of several researchers investigating on the mechanisms underlying the physiopathology of brain.

  9. Quantifying Dimer and Trimer Formation by Tri- n -butyl Phosphates in n -Dodecane: Molecular Dynamics Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Vo, Quynh N.; Dang, Liem X.; Nilsson, Mikael; Nguyen, Hung D.

    2016-07-21

    Tri-n-butyl phosphate (TBP), a representative of neutral organophosphorous ligands, is an important extractant used in solvent extraction process for the recovery of uranium and plutonium from spent nuclear fuel. Microscopic pictures of TBP isomerism and its behavior in n-dodecane diluent were investigated utilizing MD simulations with previously optimized force field parameters for TBP and n-dodecane. Potential Mean Force (PMF) calculations on a single TBP molecule show seven probable TBP isomers. Radial Distribution Functions (RDF) of TBP suggests the existence of TBP trimers at high TBP concentrations in addition to dimers. 2D PMF calculations were performed to determine the angle and distance criteria for TBP trimers. The dimerization and trimerization constants of TBP in n-dodecane were obtained and match our own experimental values using FTIR technique. The new insights into the conformational behaviors of TBP molecule as a monomer and as part of an aggregate could greatly aid the understanding of the complexation between TBP and metal ions in solvent extraction system. The U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences funded the work performed by LXD.

  10. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

    Directory of Open Access Journals (Sweden)

    Tine N Vinther

    Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

  11. Cytochrome P450 as dimerization catalyst in diketopiperazine alkaloid biosynthesis.

    Science.gov (United States)

    Saruwatari, Takayoshi; Yagishita, Fumitoshi; Mino, Takashi; Noguchi, Hiroshi; Hotta, Kinya; Watanabe, Kenji

    2014-03-21

    As dimeric natural products frequently exhibit useful biological activities, identifying and understanding their mechanisms of dimerization is of great interest. One such compound is (−)-ditryptophenaline, isolated from Aspergillus flavus, which inhibits substance P receptor for potential analgesic and anti-inflammatory activity. Through targeted gene knockout in A. flavus and heterologous yeast gene expression, we determined for the first time the gene cluster and pathway for the biosynthesis of a dimeric diketopiperazine alkaloid. We also determined that a single cytochrome P450, DtpC, is responsible not only for pyrroloindole ring formation but also for concurrent dimerization of N-methylphenylalanyltryptophanyl diketopiperazine monomers into a homodimeric product. Furthermore, DtpC exhibits relaxed substrate specificity, allowing the formation of two new dimeric compounds from a non-native monomeric precursor, brevianamide F. A radical-mediated mechanism of dimerization is proposed.

  12. Immunoglobulin Free Light Chain Dimers in Human Diseases

    Directory of Open Access Journals (Sweden)

    Batia Kaplan

    2011-01-01

    Full Text Available Immunoglobulin free light chain (FLC kappa (κ and lambda (λ isotypes exist mainly in monomeric and dimeric forms. Under pathological conditions, the level of FLCs as well as the structure of monomeric and dimeric FLCs and their dimerization properties might be significantly altered. The abnormally high fractions of dimeric FLCs were demonstrated in the serum of patients with multiple myeloma (MM and primary systemic amyloidosis (AL, as well as in the serum of anephric patients. The presence of tetra- and trimolecular complexes formed due to dimer-dimer and dimer-monomer interactions was detected in the myeloma serum. Analysis of the amyloidogenic light chains demonstrated mutations within the dimer interface, thus raising the possibility that these mutations are responsible for amyloidogenicity. Increased κ monomer and dimer levels, as well as a high κ/λ monomer ratio, were typically found in the cerebrospinal fluid from patients with multiple sclerosis (MS. In many MS cases, the elevation of κ FLCs was accompanied by an abnormally high proportion of λ dimers. This review focuses on the disease-related changes of the structure and level of dimeric FLCs, and raises the questions regarding their formation, function, and role in the pathogenesis and diagnosis of human diseases.

  13. The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm determinants in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Marco Garavaglia

    Full Text Available Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions.

  14. A 3D-analysis of cluster formation and dynamics of the X(-)-benzene (X = F, Cl, Br, I) ionic dimer solvated by Ar atoms.

    Science.gov (United States)

    Albertí, Margarita; Huarte-Larrañaga, Fermín; Aguilar, Antonio; Lucas, José M; Pirani, Fernando

    2011-05-14

    The specific influence of X(-) ions (X = F,Cl, Br, I) in the solvation process of halide-benzene (X(-)-Bz) ionic heterodimers by Ar atoms is investigated by means of molecular dynamic (MD) simulations. The gradual evolution from cluster rearrangement to solvation dynamics is discussed by considering ensembles of n (n = 1-15 and n = 30) Ar atoms around the X(-)-Bz stable ionic dimers. The potential energy surfaces employed are based on an atom/ion-atom and atom/ion-bond decomposition, which has been developed previously by some of the authors. The outcome of the dynamics is analyzed by employing radial distribution functions (RDF) and tridimensional (3D) probability densities.

  15. A facile environment-friendly one-pot two-step regioselective synthetic strategy for 3,7-diarylpyrazolo[1,5-a]pyrimidines related to zaleplon and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines assisted by KHSO[Formula: see text] in aqueous media.

    Science.gov (United States)

    Devi, Asem Satyapati; Kaping, Shunan; Vishwakarma, Jai Narain

    2015-11-01

    3-Aminopyrazoles required for the synthesis of pyrazolo[1,5-a]pyrimidines were obtained by the reaction of enaminonitriles with hydrazine hydrate. The resulting aminopyrazoles are reacted with formylated acetophenones under reflux at [Formula: see text] assisted by KHSO[Formula: see text] in aqueous media to form regioselectively 3,7-diarylpyrazolo[1,5-a]pyrimidines and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines. X-ray crystallography of selected compounds 5b and 7i further confirmed the regioselective formation of these products.

  16. Protein dimerization. Inside job.

    Science.gov (United States)

    Metzger, H

    1994-04-01

    In a sophisticated combination of genetic engineering and organic synthesis, a general method for dimerizing recombinant intracellular proteins has been devised; the usefulness of the method should now be testable.

  17. Adsorption of dimeric surfactants in lamellar silicates

    Energy Technology Data Exchange (ETDEWEB)

    Balcerzak, Mateusz; Pietralik, Zuzanna [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Domka, Ludwik [Department of Metalorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań (Poland); Skrzypczak, Andrzej [Institute of Chemical Technology, Poznań University of Technology, Berdychowo 4, 60-965 Poznań (Poland); Kozak, Maciej, E-mail: mkozak@amu.edu.pl [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

    2015-12-01

    Highlights: • The intercalation of dimeric surfactants changed the morphology of MMT samples. • XRD indicated structures formed by surfactant molecules in interlayer space. • The four-step thermal decomposition of dimeric surfactant, confirms intercalation. - Abstract: The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay – hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1′-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d{sub 001}) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH{sub 2} and CH{sub 3} groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

  18. Preparation and the Standard Enthalpy of Formation on 2-Amino-4, 6-dimethyl-pyrimidine and the Related Complexes of Zinc%2-氨基-4,6-二甲基嘧啶与锌盐配合物的制备及生成焓测定

    Institute of Scientific and Technical Information of China (English)

    陈三平; 魏青; 焦宝娟; 高胜利

    2003-01-01

    The complexes of zinc chloride and zinc nitrate with 2-amino-4, 6-dimethyl-pyrimidine (ADMP) were preparedthrough reflux in alcohol. The compositions of the complexes Zn(ADMP)2Cl2 (b) and Zn(ADMP)2(NO3)2 @ 4H2O(c) were determined by chemical and elemental analyses. The complexes were characterized by IR, XPS, 1H NMRand TG-DTG techniques. The constant-volume combustion energies of ADMP and the complexes, △cE, weredetermined by a precise rotating bomb calorimeter at 298. 15K. They were ( -3664. 53 + 1.18) kJ @ mol-1,( - 7130. 94 + 3.69) kJ @ mol-1, and ( - 7637. 87 + 5.71 ) kJ @ mol-1. Their standard enthalpies of combustion,△chΘm, and standard enthalpies of formation, △fHΘm, were calculated. They were ( -3666.39 + 1. 18)kJ @ mol-1,(-7129.70+3.69)kJ@ mol-1, (-7632.91 ±5.71)kJ@mol-1and (19.09±1.43)kJ@mol-1, (-411.96±4.03)kJ@mol-1, (-1153.28±6.02)kJ@mol-1.

  19. A previously undescribed pathway for pyrimidine catabolism.

    Science.gov (United States)

    Loh, Kevin D; Gyaneshwar, Prasad; Markenscoff Papadimitriou, Eirene; Fong, Rebecca; Kim, Kwang-Seo; Parales, Rebecca; Zhou, Zhongrui; Inwood, William; Kustu, Sydney

    2006-03-28

    The b1012 operon of Escherichia coli K-12, which is composed of seven unidentified ORFs, is one of the most highly expressed operons under control of nitrogen regulatory protein C. Examination of strains with lesions in this operon on Biolog Phenotype MicroArray (PM3) plates and subsequent growth tests indicated that they failed to use uridine or uracil as the sole nitrogen source and that the parental strain could use them at room temperature but not at 37 degrees C. A strain carrying an ntrB(Con) mutation, which elevates transcription of genes under nitrogen regulatory protein C control, could also grow on thymidine as the sole nitrogen source, whereas strains with lesions in the b1012 operon could not. Growth-yield experiments indicated that both nitrogens of uridine and thymidine were available. Studies with [(14)C]uridine indicated that a three-carbon waste product from the pyrimidine ring was excreted. After trimethylsilylation and gas chromatography, the waste product was identified by mass spectrometry as 3-hydroxypropionic acid. In agreement with this finding, 2-methyl-3-hydroxypropionic acid was released from thymidine. Both the number of available nitrogens and the waste products distinguished the pathway encoded by the b1012 operon from pyrimidine catabolic pathways described previously. We propose that the genes of this operon be named rutA-G for pyrimidine utilization. The product of the divergently transcribed gene, b1013, is a tetracycline repressor family regulator that controls transcription of the b1012 operon negatively.

  20. Assembly of Drosophila centromeric nucleosomes requires CID dimerization.

    Science.gov (United States)

    Zhang, Weiguo; Colmenares, Serafin U; Karpen, Gary H

    2012-01-27

    Centromeres are essential chromosomal regions required for kinetochore assembly and chromosome segregation. The composition and organization of centromeric nucleosomes containing the essential histone H3 variant CENP-A (CID in Drosophila) is a fundamental, unresolved issue. Using immunoprecipitation of CID mononucleosomes and cysteine crosslinking, we demonstrate that centromeric nucleosomes contain CID dimers in vivo. Furthermore, CID dimerization and centromeric targeting require a residue implicated in formation of the four-helix bundle, which mediates intranucleosomal H3 dimerization and nucleosome integrity. Taken together, our findings suggest that CID nucleosomes are octameric in vivo and that CID dimerization is essential for correct centromere assembly.

  1. Influence of Exciplex formation on the electroluminescent properties of dimeric Zn (II) bis-2-(2'-hydroxyphenyl) benzoxazole complex and monomeric Zn (II) 2-(1'-hydroxynaphthyl) benzothiazole complex

    Science.gov (United States)

    Prakash, Sattey; Anand, R. S.; Manoharan, S. Sundar

    2011-10-01

    In this paper we present the factors affecting electroluminescent properties of Zinc complexes of oxazole & thiazole derivatives. Electroluminescent spectra of the Zinc (II) complex of bis-[2-(2'-hydroxyphenyl) benzoxazole], [Zn (HPBO)2]2 and 2-(1'-hydroxynaphthyl) benzothiazole [Zn (HNBT)2] show unusual broadening and shows structural and photophysical similarity with [Zn (HPBT)2]2, a dimeric complex. The [Zn (HPBO)2]2 complex as an emissive layer in the device structure ITO /PEDOT:PSS /TPD (30nm) /[Zn (HPBO)2]2 (60nm) /BCP (6nm) /Ca (3nm) /Al (200nm) shows a broad bluish green emission, with a full width at half maxima (FWHM1˜70nm). The EL spectra is much broader compared to the PL spectra because of exciplex formation at the interfacial region between the emissive layer (EML) & hole transport layer (HTL). We also show the device performance of Zinc 2-(1'-hydroxynaphthyl) benzothiazole [Zn (HNBT)2] complex as emissive layer. Distinctly this device shows a broad greenish yellow emission with a peak maxima at 535nm and 690nm, owing to the exciplex formation between electron transport layer (ETL) and emissive layer (EML), which is in sharp contrast to the exciplex formation across the HTL-EML interface observed for the [Zn (HPBO)2]2 complex.

  2. Crystal structures of 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]-N-(naphthalen-1-yl)acetamide and 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]-N-(4-fluoro­phen­yl)acetamide

    Science.gov (United States)

    Subasri, S.; Kumar, Timiri Ajay; Sinha, Barij Nayan; Jayaprakash, Venkatesan; Viswanathan, Vijayan; Velmurugan, Devadasan

    2017-01-01

    The title compounds, C16H15N5OS, (I), and C12H12FN5OS, (II), are [(di­amino­pyrimidine)­sulfan­yl]acetamide derivatives. In (I), the pyrimidine ring is inclined to the naphthalene ring system by 55.5 (1)°, while in (II), the pyrimidine ring is inclined to the benzene ring by 58.93 (8)°. In (II), there is an intra­molecular N—H⋯N hydrogen bond and a short C—H⋯O contact. In the crystals of (I) and (II), mol­ecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers with R 2 2(8) ring motifs. In the crystal of (I), the dimers are linked by bifurcated N—H⋯(O,O) and C—H⋯O hydrogen bonds, forming layers parallel to (100). In the crystal of (II), the dimers are linked by N—H⋯O hydrogen bonds, also forming layers parallel to (100). The layers are linked by C—H⋯F hydrogen bonds, forming a three-dimensional architecture.

  3. A Novel Dimer of α-Tocopherol

    Directory of Open Access Journals (Sweden)

    Anjan Patel

    2008-01-01

    Full Text Available Decomposition of the complex 4, formed between the α-tocopherol ortho-quinone methide (2 and NMMO, by fast heating from −78∘C to 70∘C in inert solvents produces a novel α-tocopherol dimer with 6H,12H-dibenzo[b,f][1,5]dioxocine structure (5 which—in contrast to the well-known spiro-dimer of α-tocopherol (3—is symmetrical. This is the first example of a direct reaction of the highly transient zwitterionic, aromatic precursor 2a in the formation of the ortho-quinone methide 2.

  4. Synthesis of Methoxyethyl Nucleoside Dimer Phosphoramidates

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Gi Weon; Kang, Yong Han [Hanyang University, Ansan (Korea, Republic of)

    2016-05-15

    Four types of methoxyethyl (MOE) nucleoside phosphoramidites, which are categorized as second-generation building blocks of antisense oligonucleotide drugs, were synthesized. Also, three types of MOE nucleoside dimer phosphoramidites were synthesized to increase the efficiency and oligomer purity in solid phase synthesis. The block-like dimer phosphoramidites can prevent or minimize the formation of the (N-1) mer impurity, thereby affording the fabrication of pure oligonucleotides and reducing the synthesis time by performing coupling reactions in the order of 2 + 2 + 2.

  5. Superbackscattering nanoparticle dimers.

    Science.gov (United States)

    Liberal, Iñigo; Ederra, Iñigo; Gonzalo, Ramón; Ziolkowski, Richard W

    2015-07-10

    The theory and design of superbackscattering nanoparticle dimers are presented. We analytically derive the optimal configurations and the upper bound of their backscattering cross-sections. In particular, it is demonstrated that electrically small nanoparticle dimers can enhance the backscattering by a factor of 6.25 with respect to single dipolar particles. We demonstrate that optimal designs approaching this theoretical limit can be found by using a simple circuit model. The study of practical implementations based on plasmonic and high-permittivity particles has been also addressed. Moreover, the numerical examples reveal that the dimers can attain close to a fourfold enhancement of the single nanoparticle response even in the presence of high losses.

  6. Neutral pyrimidine C-H donor as anion receptor

    Institute of Scientific and Technical Information of China (English)

    袁迎雪; 吴娜娜; 韩逸飞; 宋相志; 王洪波

    2016-01-01

    Anion receptors including pyrimidine subunit were designed and synthesized and their binding abilities with various anions were investigated by fluorescence and 1H NMR titration experiments. DFT calculations provided some information for anion recognition. It is confirmed that both of two new pyrimidine anion receptors have the selectivity for Cl−.

  7. Superbackscattering Nanoparticle Dimers

    CERN Document Server

    Liberal, Iñigo; Gonzalo, Ramón; Ziolkoski, Richard W

    2015-01-01

    The theory and design of superbackscattering nanoparticle dimers are presented. We analytically derive the optimal configurations and the upper bound of their backscattering cross-sections. In particular, it is demonstrated that electrically small nanoparticle dimers can enhance the backscattering by a factor of 6.25 with respect to single dipolar particles. We demonstrate that optimal designs approaching this theoretical limit can be found by using a simple circuit model. The study of practical implementations based on plasmonic and high-permittivity particles reveal that fourfold enhancement factors might be attainable even with realistic losses.

  8. The effect of purine and pyrimidine analogues and virazole on adenovirus replication.

    Science.gov (United States)

    Scheffler, P; Haghchenas, D; Wigand, R

    1975-04-01

    The multiplication of adenovirus 19 in HeLa cells was inhibited by various purine and pyrimidine analogues and by virazole. The formation of infectious virus and of capsid proteins (haemagglutin, group-specific complement-fixing antigen) was inhibited to the same degree, while the viral cytopathic effect (CPE) was not inhibited. The reversibility of the inhibition after removal of the substances was more complete for purine than for pyrimidine analogues. The inhibition was counteracted by simulataneous addition of the corresponding nucleosides. Adenosine was more effected than guanosine against purine analogues; both were partially effective against virazole, but none of them against arabinofuranosyladenine. The time-dependence of inhibition, the ensuing eclipse period after removal of the inhibitors, and the successive application of two inhibitors led to the conclusion that most of them affect the viral multiplication mainly by inhibition of DNA synthesis. Azacytidine inhibits the synthesis of structural proteins as well.

  9. Partition-DFT on the Water Dimer

    CERN Document Server

    Gómez, Sara; Restrepo, Albeiro; Wasserman, Adam

    2016-01-01

    As is well known, the ground-state symmetry group of the water dimer switches from its equilibrium $C_{s}$-character to $C_{2h}$-character as the distance between the two oxygen atoms of the dimer decreases below $R_{\\rm O-O}\\sim 2.5$ \\AA{}. For a range of $R_{\\rm O-O}$ between 1 and 5 \\AA{}, and for both symmetries, we apply Partition Density Functional Theory (PDFT) to find the unique monomer densities that sum to the correct dimer densities while minimizing the sum of the monomer energies. We calculate the work involved in deforming the isolated monomer densities and find that it is slightly larger for the $C_s$ geometry for all $R_{\\rm O-O}$. We discuss how the PDFT densities and the corresponding partition potentials support the orbital-interaction picture of hydrogen-bond formation.

  10. A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation.

    Science.gov (United States)

    Valente, Carmen; Turacchio, Gabriele; Mariggiò, Stefania; Pagliuso, Alessandro; Gaibisso, Renato; Di Tullio, Giuseppe; Santoro, Michele; Formiggini, Fabio; Spanò, Stefania; Piccini, Daniele; Polishchuk, Roman S; Colanzi, Antonino; Luini, Alberto; Corda, Daniela

    2012-02-26

    Large pleiomorphic carriers leave the Golgi complex for the plasma membrane by en bloc extrusion of specialized tubular domains, which then undergo fission. Several components of the underlying molecular machinery have been identified, including those involved in the budding/initiation of tubular carrier precursors (for example, the phosphoinositide kinase PI(4)KIIIβ, the GTPase ARF, and FAPP2), and in the fission of these precursors (for example, PKD, CtBP1-S/BARS). However, how these proteins interact to bring about carrier formation is poorly understood. Here, we describe a protein complex that mediates carrier formation and contains budding and fission molecules, as well as other molecules, such as the adaptor protein 14-3-3γ. Specifically, we show that 14-3-3γ dimers bridge CtBP1-S/BARS with PI(4)KIIIβ, and that the resulting complex is stabilized by phosphorylation by PKD and PAK. Disrupting the association of these proteins inhibits the fission of elongating carrier precursors, indicating that this complex couples the carrier budding and fission processes.

  11. Stereo- and regio-selectivity in the photosensitized dimerization of 1, 3-dimethylthymine in solution

    Institute of Scientific and Technical Information of China (English)

    HEI Xiaoming; SONG Qinhua; TANG Wenjian; WANG Hongbo; GUO Qingxiang; YU Shuqin

    2005-01-01

    The effects of reaction pathway and temperature on stereo- and regio-selectivity of photocycloaddition of 1, 3-dimethylthymine (DMT) which gives four cyclobutane type dimers in solution using acetone as the photosensitizer, are investigated by measuring the product distribution. It is demonstrated that the ground-state aggregation between DMT molecules mainly leads to (h-t)dimers, and the diffusion-controlled triplet dimerization is favorable to the formation of (h-h) dimers.

  12. Alkane dimers interaction

    DEFF Research Database (Denmark)

    Ferrighi, Lara; Madsen, Georg Kent Hellerup; Hammer, Bjørk

    2010-01-01

    The interaction energies of a series of n-alkane dimers, from methane to decane, have been investigated with Density Functional Theory (DFT), using the MGGA-M06-L density functional. The results are compared both to the available wavefunction-based values as well as to dispersion corrected DFT...

  13. Specialized transduction of D-serine deaminase genes: formation of lysogens that yield high lambda-d dsd/lambda ratios and formation of a dimeric lambda-d dsd.

    Science.gov (United States)

    Palchaudhuri, S; McFall, E; Carothers, A M

    1976-08-01

    We have obtained two classes of double lysogens that on induction yield higher titers of lambda-d dsd transducing phage than of helper phage. One class was obtained by lysogenization of strain EM6116 (dsddelta attlambdadelta HfrC) with lambda-dsd type 2 (dsdC+ dsdO+ dsdA+, head-tail substitution). In the absence of either a normal attlambda or the homology of a chromosomal dsd region, the transducing phage integrated at other sites, at least one of which, in strain EM6177, is near the origin of HfrC. On induction, strain EM6177 yields a phage burst of 20 to 50 with a lambdadsd:lambda ratio of 10(4):1. The asnychronously high yield of lambda dsd is attributed to an efficiency of excision greater than that of lambda. The other class was obtained by lysogenization of strain EM1407 (dsdA attlambda+) with lambda-dsd type 2 (dsdO6 dsdA, partial deletion of dsdC). The DNA of mature lambda-dsd type 2 is a complete dimer. It lacks nearly all the phage late genes and b2 and carries about five bacterial genes. It could not be packaged as a monomer but is just within the packaging size limit as a dimer. Models for the derivation of these lambda dsd phages and the high-yielding lysogens are presented.

  14. Pyrimidine biosynthetic pathway of Baccillus subtilis.

    Science.gov (United States)

    Potvin, B W; Kelleher, R J; Gooder, H

    1975-08-01

    Biochemical and genetic data were obtained from a series of 51 Pyr- strains of Bacillus subtilis. The observed enzymatic deficiencies allowed the mutants to be placed into 12 clases, some of which represent defects in more than one of the six known pyrimidine biosynthetic enzymes. Mapping analysis by transformation has shown that all the Pyr- mutations are located in a single small area of the B. subtilis genome. A correlation of the biochemical defects and the genetic data has been made. Those mutations conferring similar enzymatic deficiencies were found to be contiguous on the B. subtilis map. Regulatory aspects of the pyrimidine pathway have also been investigated and are compared to previously reported results from other organisms. Evidence is presented which bears upon the possible physical association of the first three enzymes and the association of at least some of the enzymes of this pathway with particulate elements of the cell. A model for the organization of the enzymes is presented with dihydroorotate dehydrogenase as the central enzyme in a proposed aggregate.

  15. 6-(3,5-Dimethylbenzyl-5-ethyl-1-[(2-phenylethoxymethyl]pyrimidine-2,4(1H,3Hdione

    Directory of Open Access Journals (Sweden)

    Nasser R. El-Brollosy

    2012-04-01

    Full Text Available In the title pyrimidine derivative, C24H28N2O3, the uracil unit is essentially planar with an r.m.s. deviation of 0.0054 (1 Å for the eight non-H atoms. The pyrimidine ring is tilted by a dihedral angle of 77.08 (7° with respect to the aromatic ring of the 3,5-dimethylbenzyl substituent, whereas it is nearly parallel to the benzene ring of the phenethoxymethyl unit, with a dihedral angle of 8.17 (8°. An intramolecular C—H...O hydrogen bond generates an S(6 ring motif. In the crystal, molecules are linked by a pair of amide–uracil N—H...O hydrogen bonds into an inversion R22(8 dimer. These dimers are stacked along the b axis through π–π interactions with a centroid–centroid distance of 3.9517 (8 Å. Weak C—H...π interactions are also present.

  16. Dimerization of A-[alpha]-[SiNb3W9O40]7- by pH-controlled formation of individual Nb−µ-O−Nb linkages

    Science.gov (United States)

    Gyu-Shik Kim; Huadong Zeng; Wade A. Neiwert; Jennifer J. Cowan; Donald VanDerveer; Craig L. Hill; Ira A. Weinstock

    2003-01-01

    The reversible, stepwise formation of individual Nb−µ-O−Nb linkages during acid condensation of 2 equiv of A-[alpha]-[SiNb3W9O40]7- (1) to the tri-µ-oxo-bridged structure A-[alpha]-[Si2Nb6W18O77]8- (4) is demonstrated by a combination of X-ray crystallography and variable-pD solution 183W and 29Si NMR spectroscopy. Addition of DCl to a pD 8.4...

  17. Acceleration of 5-methylcytosine deamination in cyclobutane dimers by G and its implications for UV-induced C-to-T mutation hotspots.

    Science.gov (United States)

    Cannistraro, Vincent J; Taylor, John-Stephen

    2009-10-01

    Sunlight-induced C-->T mutation hotspots occur most frequently at methylated CpG sites in tumor suppressor genes and are thought to arise from translesion synthesis past deaminated cyclobutane pyrimidine dimers (CPDs). While it is known that methylation enhances CPD formation in sunlight, little is known about the effect of methylation and sequence context on the deamination of 5-methylcytosine ((m)C) and its contribution to mutagenesis at these hotspots. Using an enzymatic method, we have determined the yields and deamination rates of C and (m)C in CPDs and find that the frequency of UVB-induced CPDs correlates with the oxidation potential of the flanking bases. We also found that the deamination of T(m)C and (m)CT CPDs is about 25-fold faster when flanked by G's than by A's, C's or T's in duplex DNA and appears to involve catalysis by the O6 group of guanine. In contrast, the first deamination of either C or (m)C in AC(m)CG with a flanking G was much slower (t(1/2) >250 h) and rate limiting, while the second deamination was much faster. The observation that C(m)CG dimers deaminate very slowly but at the same time correlate with C-->T mutation hotspots suggests that their repair must be slow enough to allow sufficient time for deamination. There are, however, a greater number of single C-->T mutations than CC-->TT mutations at C(m)CG sites even though the second deamination is very fast, which could reflect faster repair of doubly deaminated dimers.

  18. The photochemistry of pyrimidine in realistic astrophysical ices and the production of nucleobases

    Energy Technology Data Exchange (ETDEWEB)

    Nuevo, Michel; Materese, Christopher K.; Sandford, Scott A., E-mail: michel.nuevo-1@nasa.gov [NASA Ames Research Center, MS 245-6, Moffett Field, CA 94035 (United States)

    2014-10-01

    Nucleobases, together with deoxyribose/ribose and phosphoric acid, are the building blocks of DNA and RNA for all known life. The presence of nucleobase-like compounds in carbonaceous chondrites delivered to the Earth raises the question of an extraterrestrial origin for the molecules that triggered life on our planet. Whether these molecules are formed in interstellar/protostellar environments, in small parent bodies in the solar system, or both, is currently unclear. Recent experiments show that the UV irradiation of pyrimidine (C{sub 4}H{sub 4}N{sub 2}) in H{sub 2}O-rich ice mixtures that contain NH{sub 3}, CH{sub 3}OH, or CH{sub 4} leads to the formation of the pyrimidine-based nucleobases uracil, cytosine, and thymine. In this work, we discuss the low-temperature UV irradiation of pyrimidine in realistic astrophysical ice mixtures containing H{sub 2}O, CH{sub 3}OH, and NH{sub 3}, with or without CH{sub 4}, to search for the production of nucleobases and other prebiotic compounds. These experiments show the presence of uracil, urea, glycerol, hexamethylenetetramine, small amino acids, and small carboxylic acids in all samples. Cytosine was only found in one sample produced from ices irradiated with a higher UV dose, while thymine was not found in any sample, even after irradiation with a higher UV dose. Results are discussed to evaluate the role of the photochemistry of pyrimidine in the inventory of organic molecules detected in meteorites and their astrophysical/astrobiological implications.

  19. Synthesis and crystal structure of N-(4-chloro­phen­yl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-amine

    Science.gov (United States)

    Repich, Hlib; Orysyk, Svitlana; Savytskyi, Pavlo; Pekhnyo, Vasyl

    2017-01-01

    The title compound, C13H12ClN5, was synthesized by the cyclization of 1-(4,6-di­methyl­pyrimidin-2-yl)-4-phenyl­thio­semicarbazide in the presence of Ni(NO3)2. The mol­ecular structure of the compound is essentially planar. In the crystal, mol­ecules form dimers via pairs of N—H⋯N hydrogen bonds between the H atom of the exocyclic amino group and the N atom at the 4-position of the triazole ring. The resulting dimers are packed into layers which are connected by π-stacking inter­actions between the aromatic systems of the pyrimidine and benzene nuclei, and between the triazole cores. PMID:28083130

  20. Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis.

    Science.gov (United States)

    Moreno-Morcillo, María; Grande-García, Araceli; Ruiz-Ramos, Alba; Del Caño-Ochoa, Francisco; Boskovic, Jasminka; Ramón-Maiques, Santiago

    2017-06-06

    CAD, the multifunctional protein initiating and controlling de novo biosynthesis of pyrimidines in animals, self-assembles into ∼1.5 MDa hexamers. The structures of the dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains of human CAD have been previously determined, but we lack information on how these domains associate and interact with the rest of CAD forming a multienzymatic unit. Here, we prove that a construct covering human DHO and ATC oligomerizes as a dimer of trimers and that this arrangement is conserved in CAD-like from fungi, which holds an inactive DHO-like domain. The crystal structures of the ATC trimer and DHO-like dimer from the fungus Chaetomium thermophilum confirm the similarity with the human CAD homologs. These results demonstrate that, despite being inactive, the fungal DHO-like domain has a conserved structural function. We propose a model that sets the DHO and ATC complex as the central element in the architecture of CAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Synthesis of novel chiral compounds of purine and pyrimidine bases

    Institute of Scientific and Technical Information of China (English)

    汪毓海; 陈庆华

    1999-01-01

    The physiologically active groups such as purine and pyrimidine bases are introduced to the asymmetric ynthesis. The optically pure compounds bearing purine and pyrimidine bases (5a—5e) were prepared via the asymetric Michael addition reaction of purines and pyrimidines as Michael donators with the chiral source 5-(R)-[(1R, 2S, 5R)-menthyloxy]-2(5H)-furanone (3a), which was prepared from the natural chiral auxiliary (-)-menthol. The synthetic method was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]D20, IR, UV, 1H NMR, 13C NMR and MS. The absolute configuration of 5a was established by X-ray crystallography. The results provided an efficient synthetic route to chiral purines and pyrimidine analogues, and offered chiral sources for further research on the physiologically active compounds of chiral nucleotides.

  2. Threshold electron attachment and electron impact ionization involving oxygen dimers

    Science.gov (United States)

    Kreil, J.; Ruf, M.-W.; Hotop, H.; Ettischer, I.; Buck, U.

    1998-12-01

    Using two different crossed-beams machines we have carried out the first quantitative study of threshold electron attachment and electron impact-induced ionization and fragmentation involving oxygen dimers (O 2) 2. In the electron attachment experiment we study electron transfer from state-selected Ar **(20d) Rydberg atoms to O 2 molecules and dimers in a skimmed supersonic beam at variable nozzle temperatures ( T0) and stagnation pressures ( p0). The relative dimer density is determined through measurements of Penning ionization by metastable Ne *(3s 3P2,0) atoms and used to estimate the absolute cross-section for O 2- formation in collisions of Ar **(20d) Rydberg atoms with O 2 dimers to be nearly 10 -17 m 2, almost four orders of magnitude larger than that for O 2- formation in collisions of Ar **(20d) Rydberg atoms with O 2 monomers. The fragmentation of the oxygen cluster beam is quantitatively characterized by the transverse helium beam scattering method which allows us to spatially separate different clusters. It is shown that in 70 eV electron impact of (O 2) 2 only 3.6(4)% of the dimers are detected as dimer ions (O 2) 2+. In additional experiments involving SF 6 clusters we show that SF 6 dimers fragment nearly completely upon 70 eV electron impact, yielding SF 5+ ions (probability for (SF 6)·SF 5+ production at most 0.3%).

  3. Clay catalysis of oligonucleotide formation: kinetics of the reaction of the 5'-phosphorimidazolides of nucleotides with the non-basic heterocycles uracil and hypoxanthine

    Science.gov (United States)

    Kawamura, K.; Ferris, J. P.

    1999-01-01

    The montmorillonite clay catalyzed condensation of activated monocleotides to oligomers of RNA is a possible first step in the formation of the proposed RNA world. The rate constants for the condensation of the phosphorimidazolide of adenosine were measured previously and these studies have been extended to the phosphorimidazolides of inosine and uridine in the present work to determine of substitution of neutral heterocycles for the basic adenine ring changes the reaction rate or regioselectivity. The oligomerization reactions of the 5'-phosphoromidazolides of uridine (ImpU) and inosine (ImpI) on montmorillonite yield oligo(U)s and oligo(I)s as long as heptamers. The rate constants for oligonucleotide formation were determined by measuring the rates of formation of the oligomers by HPLC. Both the apparent rate constants in the reaction mixture and the rate constants on the clay surface were calculated using the partition coefficients of the oligomers between the aqueous and clay phases. The rate constants for trimer formation are much greater than those dimer synthesis but there was little difference in the rate constants for the formation of trimers and higher oligomers. The overall rates of oligomerization of the phosphorimidazolides of purine and pyrimidine nucleosides in the presence of montmorillonite clay are the same suggesting that RNA formed on the primitive Earth could have contained a variety of heterocyclic bases. The rate constants for oligomerization of pyrimidine nucleotides on the clay surface are significantly higher than those of purine nucleotides since the pyrimidine nucleotides bind less strongly to the clay than do the purine nucleotides. The differences in the binding is probably due to Van der Waals interactions between the purine bases and the clay surface. Differences in the basicity of the heterocyclic ring in the nucleotide have little effect on the oligomerization process.

  4. Experimental Observation of Strongly Bound Dimers of Sulfuric Acid: Application to Nucleation in the Atmosphere

    DEFF Research Database (Denmark)

    Petaja, Tuukka; Sipila, Mikko; Paasonen, Pauli

    2011-01-01

    Sulfuric acid is a key compound in atmospheric nucleation. Here we report on the observation of a close-to-collision-limited sulfuric acid dimer formation in atmospherically relevant laboratory conditions in the absence of measurable quantities of ammonia or organics. The observed dimer formation...... compound(s) with (a) concentration(s) high enough to prevent the dimer evaporation. Such a stabilizing compound should be abundant enough in any natural environment and would therefore not limit the formation of sulfuric acid dimers in the atmosphere....

  5. Synthesis of Polyfunctionally Substituted Fused Pyrimidine Derivatives as Antimicrobial Agents

    Institute of Scientific and Technical Information of China (English)

    EISSA, Abd EI-Monem Mohamed Farag

    2008-01-01

    A variety of pyrimidine derivatives 2--4 and annulated pyrimidine derivatives 5-17 have been synthesized via a sequence of heterocyclization reaction of readily available 6-naphthyl-4-oxo-2-thioxo-1,2,3,4-tetrahydroprimi-dine-5-carbonitrile (1) with different acidic and basic reagents. The new compounds were synthesized with the aim of study of their antimicrobial activity. The structures of all synthesized compounds were elucidated by elemental analysis and spectroscopic studies.

  6. Formation of non-viable spores of Dictyostelium discoideum by UV-irradiation and caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, T.; Hazama, M.; Okaichi, K.; Nozu, K. (Nara Medical Univ., Kashihara (Japan))

    1982-09-01

    The spores formed from amoeboid cells of the wild type strain of Dictyostelium discoideum after UV-irradiation were characterized. Cell differentiation in the presence of caffeine after a fluence of 300 J/m/sup 2/ resulted in a population of spores which was 98% non-viable. The UV-irradiation did not affect the conversion of the spores to swollen spores but did affect the conversion of swollen spores to amoeboid cells. When the germination of the spores was done without caffeine, only a small effect on conversion of swollen spores to amoeboid cells and on the beginning of growth was detected. On the other hand, in the presence of caffeine, the spores had a remarkable delay in both. It was also shown that few, if any, pyrimidine dimers exist in the DNA of the non-viable spores. Possible mechanisms of formation of non-viable spores are discussed.

  7. Cold molecules: formation, trapping and spectroscopy. - Piling up of cesium dimers in a quadrupolar magnetic trap. - Spectroscopy by lack of photo-association; Molecules froides: formation, piegeage et spectroscopie. - Accumulation de dimeres de cesium dans un piege quadrupolaire magnetique. - Spectroscopie par frustration de photoassociation

    Energy Technology Data Exchange (ETDEWEB)

    Vanhaecke, N

    2003-10-15

    This thesis deals with the study of cold molecules obtained through the cold atom photo-association technique. Our study is focused both on manipulating external degrees of freedom of these Cs{sub 2} molecules and on studying their internal interactions. A quadrupolar magnetic trap of about 2.10{sup 5} cold Cs{sub 2} molecules is demonstrated. The trap lifetime is on the order of 600 ms, mainly limited by the background gas pressure. The trapped molecules are identified, which allows the determination of the trapped molecule cloud temperature, which is about 35 {mu}K. A dipolar trap is set up by the use of a focused CO{sub 2} laser beam. Moreover, this thesis describes a two-photon photo-association spectroscopy. We report the first study of two-photon photo-association line shapes, which exhibit typical Fano profiles. Taking advantage of the detailed understanding of these line shapes, we measure over one hundred high-lying level energies with an accuracy on the order of 10 MHz. Then we interpret theoretically these energies. The huge hyperfine structure of the Cesium atom binds us to solve a coupled channel Schroedinger equation for internuclear distances above 15 a{sub 0}. Hence we use an asymptotic theory to fit the potential parameters of the Cs{sub 2} dimer. We adjust those parameters by the mean of both evolutionary strategies and deterministic optimum seeking. This is followed by a careful statistics study, which leads to a very accurate determination of the Vander Waals coefficient. Moreover we report the first experimental determination of the exchange interaction amplitude. (author)

  8. Facile Syntheses of New Pyrazolo[1,5-a] pyrimidines Derivatives via Reactions of Enaminones with Aminopyrazole

    Institute of Scientific and Technical Information of China (English)

    LI Ming; WANG Shu-wen; WEN Li-rong; KE Zi-qin

    2005-01-01

    Ethyl 7-aryl-2-benzylthiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates (3a-3f) were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzylthio-4-ethoxycarbonyl-1H-pyrazole in good yields and high regioselectivity. The structures of the new compounds were fully characterized by spectroscopic measurments, elemental analysis and X-ray diffraction analysis. A plausible reaction mechanism for the formation of the title compounds was also presented.

  9. Ethyl 4-(1,3-benzodioxol-5-yl)-6-methyl-2-sulfanylidene-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

    Science.gov (United States)

    Nayak, Susanta K; Venugopala, K N; Govender, Thavendran; Kruger, Hendrik G; Maguire, Glenn E M; Row, Tayur N Guru

    2011-11-01

    In the title compound, C(15)H(16)N(2)O(4)S, the dihedral angles between the planes of the benzodioxole and ester groups and the plane of the six-membered tetra-hydro-pyrimidine ring are 89.5 (1) and 20.2 (1)°, respectively. Inter-molecular N-H⋯S hydrogen bonds assemble the mol-ecules into dimers, which are further connected via N-H⋯O inter-actions into chains parallel to [010]. Weak C-H⋯S and C-H⋯π inter-actions enhance the stability of the crystal structure.

  10. Low-energy positron scattering by pyrimidine

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Alessandra Souza; Pastega, Diego F.; Bettega, Márcio H. F., E-mail: bettega@fisica.ufpr.br [Departamento de Física, Universidade Federal do Paraná, Caixa Postal 19044, 81531-990 Curitiba, Paraná (Brazil)

    2015-12-28

    This work reports elastic integral and differential cross sections for positron collisions with pyrimidine, for energies up to 20 eV. The cross sections were computed with the Schwinger multichannel method in the static plus polarization approximation. We also employed the Born closure procedure to account for the long range potential due to the permanent dipole moment of the molecule. Our results are compared with the experimental total cross section of Zecca et al. [J. Phys. B 43, 215204 (2010)], the experimental grand-total, quasi-elastic integral and differential cross section of Palihawadana et al. [Phys. Rev. A 88, 12717 (2013)]. We also compare our results with theoretical integral and differential cross sections obtained by Sanz et al. [Phys. Rev. A 88, 62704 (2013)] with the R-matrix and the independent atom model with screening-corrected additivity rule methods, and with the results computed by Franz and Gianturco [Phys. Rev. A 88, 042711 (2013)] using model correlation-polarization potentials. The agreement between the theory and the experiment is encouraging.

  11. Electronic structure of alloxan and its dimers: QM/QD simulations and quantum chemical topology analysis.

    Science.gov (United States)

    Allehyani, Basmah H; Elroby, Shaaban A; Aziz, Saadalluh G; Hilal, Rifaat H

    2015-01-01

    This study aims to identify the origin of the extra stability of alloxan, a biologically active pyrimidine. To achieve this goal, detailed DFT computations and quantum dynamics simulations have been performed to establish the most stable conformation and the global minimum structure on the alloxan potential energy surface. The effects of the solvent, basis set, and DFT method have been examined to validate the theoretical model adopted throughout the work. Two non-covalent intermolecular dimers of alloxan, the H-bonded and dipolar dimers, have been investigated at the ωB97X-D and M06-2X levels of theory using the triple zeta 6-311++G** to establish their relative stability. Quantum chemical topology features and natural bond orbital analysis (NBO) have been performed to identify and characterize the forces that govern the structures and underlie the extra stability of alloxan.

  12. Dynamics of a bouncing dimer

    CERN Document Server

    Dorbolo, S; Tsimring, L S; Kudrolli, A

    2005-01-01

    We investigate the dynamics of a dimer bouncing on a vertically oscillated plate. The dimer, composed of two spheres rigidly connected by a light rod, exhibits several modes depending on initial and driving conditions. The first excited mode has a novel horizontal drift in which one end of the dimer stays on the plate during most of the cycle, while the other end bounces in phase with the plate. The speed and direction of the drift depend on the aspect ratio of the dimer. We employ event-driven simulations based on a detailed treatment of frictional interactions between the dimer and the plate in order to elucidate the nature of the transport mechanism in the drift mode.

  13. Novel Air Stable Organic Radical Semiconductor of Dimers of Dithienothiophene, Single Crystals, and Field-Effect Transistors.

    Science.gov (United States)

    Zhang, Hantang; Dong, Huanli; Li, Yang; Jiang, Wei; Zhen, Yonggang; Jiang, Lang; Wang, Zhaohui; Chen, Wei; Wittmann, Angela; Hu, Wenping

    2016-09-01

    Singly linked and vinyl-linked dimers of dithienothiophenes exhibit different electronic behaviors. Single crystals of the singly linked dimer show a high conductivity of 0.265 S cm(-1) , five orders of magnitude higher than that of the vinyl-linked dimer. The huge increase in the hole density of singly linked dimers results from the formation of radicals, which can be reversibly tuned by facile thermal de-doping.

  14. A model for triplet mutation formation based on error-prone translesional DNA synthesis opposite UV photolesions.

    Science.gov (United States)

    Ikehata, Hironobu; Ono, Tetsuya; Tanaka, Kiyoji; Todo, Takeshi

    2007-05-01

    A triplet mutation is defined as multiple base substitutions or frameshifts within a three-nucleotide sequence which includes a dipyrimidine sequence. Triplet mutations have recently been identified as a new type of UV-specific mutation, although the mechanism of their formation is unknown. A total of 163 triplet mutations were identified through an extensive search of previously published data on UV-induced mutations, including mutations from skin, skin cancer, and cultured mammalian cells. Seven common patterns of sequence changes were found: Type I, NTC-->TTT; Type IIa, NCC-->PyTT or PyCT (Py, pyrimidine); Type IIb, TCC-->PuTT or PuCT (Pu, purine); Type III, NCC-->NAT or NTA; Type IV, NTT-->AAT; Type Va, NCT-->NTX; and Type Vb, PuCT-->XTT (N and X, independent anonymous bases). Furthermore, it is suggested that the type of UV lesion responsible for each of these triplet mutation classes are (a) pyrimidine(6-4)pyrimidone photoproducts for Types I, IIb, III, IV and Vb, (b) cyclobutane pyrimidine dimers for Type Va, and (c) Dewar valence isomers for Types IIa and IIb. These estimations are based primarily on results from previous studies using photolyases specific for each type of UV lesion. A model is proposed to explain the formation of each type of triplet mutation, based on error-prone translesional DNA synthesis opposite UV-specific photolesions. The model is largely consistent with the 'A-rule', and predicts error-prone insertions not only opposite photolesions but also opposite the undamaged template base one-nucleotide downstream from the lesions.

  15. Privileged substructure-based diversity-oriented synthesis pathway for diverse pyrimidine-embedded polyheterocycles

    DEFF Research Database (Denmark)

    Kim, Heejun; Thanh Tung, Truong; Park, Seung Bum

    2013-01-01

    A new diversity-oriented synthesis pathway for the fabrication of a pyrimidine-embedded polyheterocycles library was developed for potential interactions with diverse biopolymers. Five different pyrimidine-embedded core skeletons were synthesized from ortho-alkynylpyrimidine carbaldehydes...

  16. UV spectra of benzene isotopomers and dimers in helium nanodroplets

    Science.gov (United States)

    Schmied, Roman; ćarçabal, Pierre; Dokter, Adriaan M.; Lonij, Vincent P. A.; Lehmann, Kevin K.; Scoles, Giacinto

    2004-08-01

    We report spectra of various benzene isotopomers and their dimers in helium nanodroplets in the region of the first Herzberg-Teller allowed vibronic transition 601 1B2u←1A1g (the A00 transition) at ˜260 nm. Excitation spectra have been recorded using both beam depletion detection and laser-induced fluorescence. Unlike for many larger aromatic molecules, the monomer spectra consist of a single "zero-phonon" line, blueshifted by ˜30 cm-1 from the gas phase position. Rotational band simulations show that the moments of inertia of C6H6 in the nanodroplets are at least six-times larger than in the gas phase. The dimer spectra present the same vibronic fine structure (though modestly compressed) as previously observed in the gas phase. The fluorescence lifetime and quantum yield of the dimer are found to be equal to those of the monomer, implying substantial inhibition of excimer formation in the dimer in helium.

  17. Uptake and incorporation of pyrimidines in Euglena gracilis.

    Science.gov (United States)

    Wasternack, C H

    1976-08-01

    In photoorganotrophically grown cells of Euglena gracilis the uptake and incorporation degree of 12 different pyrimidines were tested. The rate of uptake of pyrimidines has distinct maxima in the late log phase and in the stationary phase of cell multiplication. The kinetics of uptake are linear in the first 2 h, do not show saturation at various concentrations and increase with the concetrations. No accumulation of the pyrimidines at various concentrations could be observed in the first 2 h of incubation. Membrane inhibitors as uranyl acetate inhibit the uptake of the reference substance alpha-AIB, which is wellknown transported by an active transport mechanism, but have no effect on uptake rate of uracil and cytosine. It could not be observed an energy requirement tested in temperature dependence and with electron transport inhibitors. Uptake of uridine, uracil, barbituric acid and alpha-AIB is inhibited by cycloheximide in a different manner after 5 - 10 min.

  18. Significance and Biological Importance of Pyrimidine in the Microbial World

    Directory of Open Access Journals (Sweden)

    Vinita Sharma

    2014-01-01

    Full Text Available Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions. The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities which can treat microbial infections. The present review aims to focus on account of important chemical moiety, that is, pyrimidine and its various derivatives as antimicrobial agents. In the current studies we represent more than 200 pyrimidines as antimicrobial agents with different mono-, di-, tri-, and tetrasubstituted classes along with in vitro antimicrobial activities of pyrimidines derivatives which can facilitate the development of more potent and effective antimicrobial agents.

  19. Photo association in metastable helium in the vicinity of the Bose-Einstein condensation and production of giant dimers; Photo-association de l'helium metastable au voisinage de la condensation de Bose-Einstein et formation de dimeres geants

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, J

    2003-11-15

    In the vicinity of Bose-Einstein condensation, the collisional properties of a dilute gas of metastable helium (He{sub 2}{sup 3}S) are governed by the rate of ionizing Penning collisions and the s-wave scattering length. In order to investigate these properties, we have carried out new photo-association experiments in which a pair of free atoms absorbs a photon to produce a molecule in an excited electronic state. In particular, we have observed 'giant dimers' for which the autoionizing process is inhibited. Accurate spectra have been acquired by the use of an original 'calorimetric' detection scheme. In addition, we have calculated long-range electronic potentials for the 2{sup 3} S + 2{sup 3} P system. Our asymptotic approach is described in detail, which reproduces the measured binding energies of the giant dimers with very good accuracy. (author)

  20. Dimeric boronates derived from the reaction of schiff bases and boronic acids

    Energy Technology Data Exchange (ETDEWEB)

    Barba, Victor [Universidad Autonoma del Estado de Morelos, Cuernavaca, Morelos (Mexico). Centro de Investigaciones Quimicas; Santillan, Rosa; Farfan, Norberto [Instituto Politecnico Nacional (IPN), Mexico, D.F. (Mexico). Centro de Investigacion y de Estudios Avanzados. Dept. de Quimica]. E-mail: jfarfan@cinvestav.mx

    2005-05-15

    The one-pot synthesis of dimeric boron complexes is reported. The compounds were obtained by reaction of Schiff bases (tridentate ligands) with trans-{beta}-phenylvinylboronic acid, 3-thiopheneboronic acid and methylboronic acid. Building of the dimeric structures is favored by the presence of intramolecular N{yields}B coordination bonds, resulting in the formation of ten-membered ring heterocycles. An X-ray crystallographic analysis for one of them confirmed the dimeric nature of these compounds. (author)

  1. Universal dimer-dimer scattering in lattice effective field theory

    CERN Document Server

    Elhatisari, Serdar; Lee, Dean; Meißner, Ulf-G; Rupak, Gautam

    2016-01-01

    We consider two-component fermions with short-range interactions and large scattering length. This system has universal properties that are realized in many different fields including atomic, nuclear and particle physics. In the limit of large fermion-fermion scattering length $a_\\mathrm{ff}$ and zero range interaction, all properties of the system scale proportionally with the only length scale $a_\\mathrm{ff}$. We consider the case where there are bound dimers and calculate the scattering phase shifts for the two-dimer system near threshold using lattice effective field theory. From the scattering phase shifts, we extract the universal dimer-dimer scattering length $a_\\mathrm{dd}/a_\\mathrm{ff}=0.645(89)$ and effective range $r_\\mathrm{dd}/a_\\mathrm{ff}=-0.413(79)$.

  2. Detection of alpha-helical coiled-coil dimer formation by spin-labeled synthetic peptides: a model parallel coiled-coil peptide and the antiparallel coiled coil formed by a replica of the ProP C-terminus.

    Science.gov (United States)

    Hillar, Alexander; Tripet, Brian; Zoetewey, David; Wood, Janet M; Hodges, Robert S; Boggs, Joan M

    2003-12-30

    Electron paramagnetic resonance spectroscopy was used to determine relative peptide orientation within homodimeric, alpha-helical coiled-coil structures. Introduction of cysteine (Cys) residues into peptides/proteins for spin labeling allows detection of their oligomerization from exchange broadening or dipolar interactions between residues within 25 A of each other. Two synthetic peptides containing Cys substitutions were used: a 35-residue model peptide and the 30-residue ProP peptide. The model peptide is known to form a stable, parallel homodimeric coiled coil, which is partially destabilized by Cys substitutions at heptad a and d positions (peptides C30a and C33d). The ProP peptide, a 30-residue synthetic peptide, corresponds to residues 468-497 of osmoregulatory transporter ProP from Escherichia coli. It forms a relatively unstable, homodimeric coiled coil that is predicted to be antiparallel in orientation. Cys was introduced in heptad g positions of the ProP peptide, near the N-terminus (K473C, creating peptide C473g) or closer to the center of the sequence (E480C, creating peptide C480g). In contrast to the destabilizing effect of Cys substitution at the core heptad a or d positions of model peptides C30a and C33d, circular dichroism spectroscopy showed that Cys substitutions at the heptad g positions of the ProP peptide had little or no effect on coiled-coil stability. Thermal denaturation analysis showed that spin labeling increased the stability of the coiled coil for all peptides. Strong exchange broadening was detected for both C30a and C33d, in agreement with a parallel structure. EPR spectra of C480g had a large hyperfine splitting of about 90 G, indicative of strong dipole-dipole interactions and a distance between spin-labeled residues of less than 9 A. Spin-spin interactions were much weaker for C473g. These results supported the hypothesis that the ProP peptide primarily formed an antiparallel coiled coil, since formation of a parallel dimer

  3. Irradiation of pyrimidine in pure H2O ice with high-energy ultraviolet photons.

    Science.gov (United States)

    Nuevo, Michel; Chen, Yu-Jung; Hu, Wei-Jie; Qiu, Jun-Ming; Wu, Shang-Ruei; Fung, Hok-Sum; Chu, Ching-Chi; Yih, Tai-Sone; Ip, Wing-Huen; Wu, C-Y Robert

    2014-02-01

    The detection of nucleobases, the informational subunits of DNA and RNA, in several meteorites suggests that these compounds of biological interest were formed via astrophysical, abiotic processes. This hypothesis is in agreement with recent laboratory studies of irradiation of pyrimidine in H2O-rich ices with vacuum UV photons emitted by an H2-discharge lamp in the 6.9-11.3 eV (110-180 nm) range at low temperature, shown to lead to the abiotic formation of several compounds including the nucleobases uracil, cytosine, and thymine. In this work, we irradiated H2O:pyrimidine ice mixtures under astrophysically relevant conditions (14 K, ≤10(-9) torr) with high-energy UV photons provided by a synchrotron source in three different ranges: the 0(th) order light (4.1-49.6 eV, 25-300 nm), the He i line (21.2 eV, 58.4 nm), and the He ii line (40.8 eV, 30.4 nm). The photodestruction of pyrimidine was monitored with IR spectroscopy, and the samples recovered at room temperature were analyzed with liquid and gas chromatographies. Uracil and its precursor 4(3H)-pyrimidone were found in all samples, with absolute and relative abundances varying significantly from one sample to another. These results support a scenario in which compounds of biological interest can be formed and survive in environments subjected to high-energy UV radiation fields.

  4. Contrasting reactions of hydrated electron and formate radical with 2-thio analogues of cytosine and uracil.

    Science.gov (United States)

    Prasanthkumar, Kavanal P; Alvarez-Idaboy, Juan R; Kumar, Pavitra V; Singh, Beena G; Priyadarsini, K Indira

    2016-10-19

    2-Thiocytosine (TC) and 2-thiouracil (TU) were subjected to hydrated electron (eaq(-)), formate radical (CO2˙(-)) and 2-hydroxypropan-2-yl radical ((CH3)2˙COH) reactions in aqueous medium. Transients were characterized by absorption spectroscopy and the experimental findings were rationalized by DFT calculations at LC-ωPBE and M06-2X levels using a 6-311+G(d,p) basis set and SMD solvation. In eaq(-) reactions, a ring N-atom protonated radical of TC and an exocyclic O-atom protonated radical of TU were observed via addition of eaq(-) and subsequent protonation by solvent molecules. However, two competing but simultaneous mechanisms are operative in CO2˙(-) reactions with TC and TU. The first one corresponds to formations of N(O)-atom protonated radicals (similar to eaq(-) reactions); the second mechanism led to 2 center-3 electron, sulfur-sulfur bonded neutral dimer radicals, TCdim˙ and TUdim˙. DFT calculations demonstrated that H-abstraction by CO2˙(-) from TC(TU) results in S-centered radical which upon combination with TC(TU) provide the dimer radical. In some cases, DFT energy profiles were further validated by CBS-QB3//M06-2X calculations. This is the first time report for a contradictory behavior in the mechanisms of eaq(-) and CO2˙(-) reactions with any pyrimidines or their thio analogues.

  5. Tetramerization reinforces the dimer interface of MnSOD.

    Directory of Open Access Journals (Sweden)

    Yuewei Sheng

    Full Text Available Two yeast manganese superoxide dismutases (MnSOD, one from Saccharomyces cerevisiae mitochondria (ScMnSOD and the other from Candida albicans cytosol (CaMnSODc, have most biochemical and biophysical properties in common, yet ScMnSOD is a tetramer and CaMnSODc is a dimer or "loose tetramer" in solution. Although CaMnSODc was found to crystallize as a tetramer, there is no indication from the solution properties that the functionality of CaMnSODc in vivo depends upon the formation of the tetrameric structure. To elucidate further the functional significance of MnSOD quaternary structure, wild-type and mutant forms of ScMnSOD (K182R, A183P mutant and CaMnSODc (K184R, L185P mutant with the substitutions at dimer interfaces were analyzed with respect to their oligomeric states and resistance to pH, heat, and denaturant. Dimeric CaMnSODc was found to be significantly more subject to thermal or denaturant-induced unfolding than tetrameric ScMnSOD. The residue substitutions at dimer interfaces caused dimeric CaMnSODc but not tetrameric ScMnSOD to dissociate into monomers. We conclude that the tetrameric assembly strongly reinforces the dimer interface, which is critical for MnSOD activity.

  6. Multi-Component Protein - Protein Docking Based Protocol with External Scoring for Modeling Dimers of G Protein-Coupled Receptors.

    Science.gov (United States)

    Kaczor, Agnieszka A; Guixà-González, Ramon; Carrió, Pau; Poso, Antti; Dove, Stefan; Pastor, Manuel; Selent, Jana

    2015-04-01

    In order to apply structure-based drug design techniques to GPCR complexes, it is essential to model their 3D structure. For this purpose, a multi-component protocol was derived based on protein-protein docking which generates populations of dimers compatible with membrane integration, considering all reasonable interfaces. At the next stage, we applied a scoring procedure based on up to eleven different parameters including shape or electrostatics complementarity. Two methods of consensus scoring were performed: (i) average scores of 100 best scored dimers with respect to each interface, and (ii) frequencies of interfaces among 100 best scored dimers. In general, our multi-component protocol gives correct indications for dimer interfaces that have been observed in X-ray crystal structures of GPCR dimers (opsin dimer, chemokine CXCR4 and CCR5 dimers, κ opioid receptor dimer, β1 adrenergic receptor dimer and smoothened receptor dimer) but also suggests alternative dimerization interfaces. Interestingly, at times these alternative interfaces are scored higher than the experimentally observed ones suggesting them to be also relevant in the life cycle of studied GPCR dimers. Further results indicate that GPCR dimer and higher-order oligomer formation may involve transmembrane helices (TMs) TM1-TM2-TM7, TM3-TM4-TM5 or TM4-TM5-TM6 but not TM1-TM2-TM3 or TM2-TM3-TM4 which is in general agreement with available experimental and computational data.

  7. Collisional properties of weakly bound heteronuclear dimers

    NARCIS (Netherlands)

    Marcelis, B.; Kokkelmans, S.J.J.M.F.; Shlyapnikov, G.V.; Petrov, D.S.

    2008-01-01

    We consider collisional properties of weakly bound heteronuclear molecules (dimers) formed in a two-species mixture of atoms with a large mass difference. We focus on dimers containing light fermionic atoms as they manifest collisional stability due to an effective dimer-dimer repulsion originating

  8. Reversible Dimerization of Acid-Denatured ACBP Controlled by Helix A4

    DEFF Research Database (Denmark)

    Fieber, Wolfgang; Kragelund, Birthe Brandt; Meldal, Morten Peter;

    2005-01-01

    of dimers and revealed a cooperative stabilization of helix A4 in this process. This emphasizes its special role in the structure formation in the denatured state of ACBP. No dimers are formed in the presence of guanidine hydrochloride, which underlines the fundamental difference between the nature...

  9. Nucleotide metabolism in Lactococcus lactis: Salvage pathways of exogenous pyrimidines

    DEFF Research Database (Denmark)

    Martinussen, Jan; Andersen, Paal Skytt; Hammer, Karin

    1994-01-01

    By measuring enzyme activities in crude extracts and studying the effect of toxic analogs (5-fluoropyrimidines) on cell growth, the metabolism of pyrimidines in Lactococcus lactis was analyzed. Pathways by which uracil, uridine, deoxyuridine, cytidine, and deoxycytidine are metabolized in L. lact...

  10. Intramolecular inverse electron demand Diels-Alder reactions of pyrimidines.

    NARCIS (Netherlands)

    Frissen, A.E.

    1990-01-01

    This thesis deals with the intramolecular inverse electron demand Diels-Alder reaction of pyrimidines. The main objective of the study was to investigate the synthetic applicability of this reaction and to get more insight in the electronic and steric effects which determine the reactivity of compou

  11. Dimerization of a flocculent protein from Moringa oleifera: experimental evidence and in silico interpretation.

    Science.gov (United States)

    Pavankumar, Asalapuram R; Kayathri, Rajarathinam; Murugan, Natarajan A; Zhang, Qiong; Srivastava, Vaibhav; Okoli, Chuka; Bulone, Vincent; Rajarao, Gunaratna K; Ågren, Hans

    2014-01-01

    Many proteins exist in dimeric and other oligomeric forms to gain stability and functional advantages. In this study, the dimerization property of a coagulant protein (MO2.1) from Moringa oleifera seeds was addressed through laboratory experiments, protein-protein docking studies and binding free energy calculations. The structure of MO2.1 was predicted by homology modelling, while binding free energy and residues-distance profile analyses provided insight into the energetics and structural factors for dimer formation. Since the coagulation activities of the monomeric and dimeric forms of MO2.1 were comparable, it was concluded that oligomerization does not affect the biological activity of the protein.

  12. Vortexlike topological defects in nematic colloids: chiral colloidal dimers and 2D crystals.

    Science.gov (United States)

    Tkalec, U; Ravnik, M; Zumer, S; Musevic, I

    2009-09-18

    We show that chiral ordering of the underlying complex fluid strongly influences defect formation and colloidal interactions. Nonsingular defect loops with a topological charge -2 are observed, with a cross section identical to hyperbolic vortices in magnetic systems. These loops are binding spontaneously formed pairs of colloidal particles and dimers, which are chiral objects. Chiral dimer-dimer interaction weakly depends on the chirality of dimers and leads to the assembly of 2D nematic colloidal crystals of pure or "mixed" chirality, intercalated with a lattice of nonsingular vortexlike defects.

  13. Intermolecular disulfide bond influences unphosphorylated STAT3 dimerization and function.

    Science.gov (United States)

    Butturini, Elena; Gotte, Giovanni; Dell'Orco, Daniele; Chiavegato, Giulia; Marino, Valerio; Canetti, Diana; Cozzolino, Flora; Monti, Maria; Pucci, Piero; Mariotto, Sofia

    2016-10-01

    Signal transducer and activator of transcription 3 (STAT3) is a transcription factor activated by the phosphorylation of tyrosine 705 in response to many cytokines and growth factors. Recently, the roles for unphosphorylated STAT3 (U-STAT3) have been described in response to cytokine stimulation, in cancers, and in the maintenance of heterochromatin stability. It has been reported that U-STAT3 dimerizes, shuttles between the cytoplasm and nucleus, and binds to DNA, thereby driving genes transcription. Although many reports describe the active role of U-STAT3 in oncogenesis in addition to phosphorylated STAT3, the U-STAT3 functional pathway remains elusive.In this report, we describe the molecular mechanism of U-STAT3 dimerization, and we identify the presence of two intermolecular disulfide bridges between Cys367 and Cys542 and Cys418 and Cys426, respectively. Recently, we reported that the same cysteines contribute to the redox regulation of STAT3 signaling pathway both in vitro and in vivo The presence of these disulfides is here demonstrated to largely contribute to the structure and the stability of U-STAT3 dimer as the dimeric form rapidly dissociates upon reduction in the S-S bonds. In particular, the Cys367-Cys542 disulfide bridge is shown to be critical for U-STAT3 DNA-binding activity. Mutation of the two Cys residues completely abolishes the DNA-binding capability of U-STAT3. Spectroscopic investigations confirm that the noncovalent interactions are sufficient for proper folding and dimer formation, but that the interchain disulfide bonds are crucial to preserve the functional dimer. Finally, we propose a reaction scheme of U-STAT3 dimerization with a first common step followed by stabilization through the formation of interchain disulfide bonds. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  14. Threshold electron attachment and electron impact ionization involving oxygen dimers

    Energy Technology Data Exchange (ETDEWEB)

    Kreil, J.; Ruf, M.-W.; Hotop, H. [Fachbereich Physik, Universitaet Kaiserslautern, D-67653 Kaiserslautern (Germany); Ettischer, I.; Buck, U. [Max-Planck-Institut fuer Stroemungsforschung, Bunsenstrasse 10, D-37073 Goettingen (Germany)

    1998-12-15

    Using two different crossed-beams machines we have carried out the first quantitative study of threshold electron attachment and electron impact-induced ionization and fragmentation involving oxygen dimers (O{sub 2}){sub 2}. In the electron attachment experiment we study electron transfer from state-selected Ar{sup **}(20d) Rydberg atoms to O{sub 2} molecules and dimers in a skimmed supersonic beam at variable nozzle temperatures (T{sub 0}) and stagnation pressures (p{sub 0}). The relative dimer density is determined through measurements of Penning ionization by metastable Ne{sup *}(3s {sup 3}P{sub 2,0}) atoms and used to estimate the absolute cross-section for O{sub 2}{sup -} formation in collisions of Ar{sup **}(20d) Rydberg atoms with O{sub 2} dimers to be nearly 10{sup -17} m{sup 2}, almost four orders of magnitude larger than that for O{sub 2}{sup -} formation in collisions of Ar{sup **}(20d) Rydberg atoms with O{sub 2} monomers. The fragmentation of the oxygen cluster beam is quantitatively characterized by the transverse helium beam scattering method which allows us to spatially separate different clusters. It is shown that in 70 eV electron impact of (O{sub 2}){sub 2} only 3.6(4)% of the dimers are detected as dimer ions (O{sub 2}){sub 2}{sup +}. In additional experiments involving SF{sub 6} clusters we show that SF{sub 6} dimers fragment nearly completely upon 70 eV electron impact, yielding SF{sub 5}{sup +} ions (probability for (SF{sub 6}){center_dot}SF{sub 5}{sup +} production at most 0.3%). (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  15. Products and mechanism of acene dimerization. A computational study.

    Science.gov (United States)

    Zade, Sanjio S; Zamoshchik, Natalia; Reddy, A Ravikumar; Fridman-Marueli, Galit; Sheberla, Dennis; Bendikov, Michael

    2011-07-20

    The high reactivity of acenes can reduce their potential applications in the field of molecular electronics. Although pentacene is an important material for use in organic field-effect transistors because of its high charge mobility, its reactivity is a major disadvantage hindering the development of pentacene applications. In this study, several reaction pathways for the thermal dimerization of acenes were considered computationally. The formation of acene dimers via a central benzene ring and the formation of acene-based polymers were found to be the preferred pathways, depending on the length of the monomer. Interestingly, starting from hexacene, acene dimers are thermodynamically disfavored products, and the reaction pathway is predicted to proceed instead via a double cycloaddition reaction (polymerization) to yield acene-based polymers. A concerted asynchronous reaction mechanism was found for benzene and naphthalene dimerization, while a stepwise biradical mechanism was predicted for the dimerization of anthracene, pentacene, and heptacene. The biradical mechanism for dimerization of anthracene and pentacene proceeds via syn or anti transition states and biradical minima through stepwise biradical pathways, while dimerization of heptacene proceeds via asynchronous ring closure of the complex formed by two heptacene molecules. The activation barriers for thermal dimerization decrease rapidly with increasing acene chain length and are calculated (at M06-2X/6-31G(d)+ZPVE) to be 77.9, 57.1, 33.3, -0.3, and -12.1 kcal/mol vs two isolated acene molecules for benzene, naphthalene, anthracene, pentacene, and heptacene, respectively. If activation energy is calculated vs the initially formed complex of two acene molecules, then the calculated barriers are 80.5, 63.2, 43.7, 16.7, and 12.3 kcal/mol. Dimerization is exothermic from anthracene onward, but it is endothermic at the terminal rings, even for heptacene. Phenyl substitution at the most reactive meso

  16. Stabilities and Spectroscopy of Hydrogen Bonding Complexes Formed by 2,4-Bis(acrylamido)pyrimidines

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ye; LI Ting; TENG Qi-Wen

    2008-01-01

    Hydrogen bonds play important roles to living organisms containing pyrimidine-based derivatives.The electronic structures of the hydrogen bonding complexes formed by 2,4-bis(acrylamido)pyrimidine (2,4-BAAP) derivatives with 1-substituted uracil were studied using Austin Model 1 (AMl) and density function theory (DFT) methods.The UV and NMR spectra of the complexes were calculated with the INDO/CIS (configuration interaction for singlet in intermediate neglect of differential overlap) and B3LYP/6-31G(d)methods.It was shown that the complexes could be formed via the triple hydrogen bonding between two monomers owing to the negative binding energies.The binding energies of the complexes were weakened in the presence of substituents,but this weakening effect depended on the simultaneous influence of the electronic and steric effects.The binding energies of the complexes were also decreased owing to the formation of the isomeric complexes in the presence of piperidyl on 2,4-BAAP.The energy gaps of the complexes were lessened in the presence of electron-donating groups.Holes and electrons were easily injected to the complexes due to the extension of the conjugation chain.The first UV absorptions of the complexes relative to those of the parent compound were red-shifted because of the narrow energy gaps.The chemical shifts of the carbon atoms on the C=O bonds in the complexes were changed downfield.

  17. OCLI-023, a Novel Pyrimidine Compound, Suppresses Osteoclastogenesis In Vitro and Alveolar Bone Resorption In Vivo

    Science.gov (United States)

    Kim, Ju Ang; Lee, Doohyun; Kim, Nam Doo; Shin, Hong-In; Bae, Yong Chul; Park, Eui Kyun

    2017-01-01

    An abnormal increase in osteoclast differentiation and activation results in various bone-resorptive diseases, including periodontitis, rheumatoid arthritis, and osteoporosis. Chemical compounds containing pyrimidine ring have been shown to regulate a variety of biological processes. Therefore, in order to identify an antiresorptive agent, we synthesized a series of pyrimidine ring-containing chemical compounds, and found that OCLI-023 suppressed the differentiation and activation of osteoclasts in vitro. OCLI-023 directly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced differentiation of bone marrow macrophages into osteoclasts, without a cytotoxic response. OCLI-023 also downregulated the RANKL-induced mRNA expression of osteoclast markers as well as inhibited the formation of actin rings and resorption pits. OCLI-023 attenuated the RANKL-induced activation of c-Jun N-terminal kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. In a mouse model of periodontitis, ligature induced an increase of distance between cementoenamel junction (CEJ) and alveolar bone crest (ABC) in the second molar, and OCLI-023 significantly reduced it. Histological analysis showed ligature-induced increase of osteoclast numbers was also significantly reduced by OCLI-023. These data demonstrated the inhibitory effect of OCLI-023 on osteoclast differentiation and activity of osteoclasts in vitro, as well as on ligature-induced bone loss in vivo, and OCLI-023 can be proposed as a novel anti-resorptive compound. PMID:28085946

  18. Synthesis of a distinct water dimer inside fullerene C70

    Science.gov (United States)

    Zhang, Rui; Murata, Michihisa; Aharen, Tomoko; Wakamiya, Atsushi; Shimoaka, Takafumi; Hasegawa, Takeshi; Murata, Yasujiro

    2016-05-01

    The water dimer is an ideal chemical species with which to study hydrogen bonds. Owing to the equilibrium between the monomer and oligomer structure, however, selective generation and separation of a genuine water dimer has not yet been achieved. Here, we report a synthetic strategy that leads to the successful encapsulation of one or two water molecules inside fullerene C70. These endohedral C70 compounds offer the opportunity to study the intrinsic properties of a single water molecule without any hydrogen bonding, as well as an isolated water dimer with a single hydrogen bond between the two molecules. The unambiguously determined off-centre position of water in (H2O)2@C70 by X-ray diffraction provides insights into the formation of (H2O)2@C70. Subsequently, the 1H NMR spectroscopic measurements for (H2O)2@C70 confirmed the formation of a single hydrogen bond rapidly interchanging between the encapsulated water dimer. Our theoretical calculations revealed a peculiar cis-linear conformation of the dimer resulting from confinement effects inside C70.

  19. Regulation of primate lentiviral RNA dimerization by structural entrapment

    Directory of Open Access Journals (Sweden)

    Lodmell J Stephen

    2008-07-01

    Full Text Available Abstract Background Genomic RNA dimerization is an important process in the formation of an infectious lentiviral particle. One of the signals involved is the stem-loop 1 (SL1 element located in the leader region of lentiviral genomic RNAs which also plays a role in encapsidation and reverse transcription. Recent studies revealed that HIV types 1 and 2 leader RNAs adopt different conformations that influence the presentation of RNA signals such as SL1. To determine whether common mechanisms of SL1 regulation exist among divergent lentiviral leader RNAs, here we compare the dimerization properties of SIVmac239, HIV-1, and HIV-2 leader RNA fragments using homologous constructs and experimental conditions. Prior studies from several groups have employed a variety of constructs and experimental conditions. Results Although some idiosyncratic differences in the dimerization details were observed, we find unifying principles in the regulation strategies of the three viral RNAs through long- and short-range base pairing interactions. Presentation and efficacy of dimerization through SL1 depends strongly upon the formation or dissolution of the lower stem of SL1 called stem B. SL1 usage may also be down-regulated by long-range interactions involving sequences between SL1 and the first codons of the gag gene. Conclusion Despite their sequence differences, all three lentiviral RNAs tested in this study showed a local regulation of dimerization through the stabilization of SL1.

  20. Dimer-tetramer transition controls RUNX1/ETO leukemogenic activity.

    Science.gov (United States)

    Wichmann, Christian; Becker, Yvonne; Chen-Wichmann, Linping; Vogel, Vitali; Vojtkova, Anna; Herglotz, Julia; Moore, Sandra; Koch, Joachim; Lausen, Jörn; Mäntele, Werner; Gohlke, Holger; Grez, Manuel

    2010-07-29

    RUNX1/ETO, the fusion protein resulting from the chromosomal translocation t(8;21), is one of the most frequent translocation products in acute myeloid leukemia. Several in vitro and in vivo studies have shown that the homo-tetramerization domain of ETO, the nervy homology region 2 (NHR2), is essential for RUNX1/ETO oncogenic activity. We analyzed the energetic contribution of individual amino acids within the NHR2 to RUNX1/ETO dimer-tetramer transition and found a clustered area of 5 distinct amino acids with strong contribution to the stability of tetramers. Substitution of these amino acids abolishes tetramer formation without affecting dimer formation. Similar to RUNX1/ETO monomers, dimers failed to bind efficiently to DNA and to alter expression of RUNX1-dependent genes. RUNX1/ETO dimers do not block myeloid differentiation, are unable to enhance the self-renewal capacity of hematopoietic progenitors, and fail to induce leukemia in a murine transplantation model. Our data reveal the existence of an essential structural motif (hot spot) at the NHR2 dimer-tetramer interface, suitable for a molecular intervention in t(8;21) leukemias.

  1. Annellation of Triazole and Tetrazole Systems onto Pyrrolo[2,3-d]pyrimidines: Synthesis of Tetrazolo[1,5-c]-pyrrolo[3,2-e]-pyrimidines and Triazolo[1,5-c]pyrrolo-[3,2-e]pyrimidines as Potential Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Rina D. Shah

    2002-07-01

    Full Text Available Syntheses of several novel 4-chloropyrrolo[2,3-d]pyrimidines (1, 4-hydrazinopyrrolo[2,3-d]pyrimidines (2 and 3-amino-4-iminopyrrolo[2,3-d]pyrimidines (7 and their use in the synthesis of tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines (3 and triazolo[1,5-c]pyrrolo[3,2-e]pyrimidines (4 required for biological screening are reported.

  2. Crystal structure of (S-5,7-diphenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine

    Directory of Open Access Journals (Sweden)

    Ivy K. Price

    2015-04-01

    Full Text Available The title compound, C16H13N5, was synthesized by coupling aminotetrazole with chalcone in the presence of an amine organocatalyst derived from chincona alkaloid. There are two molecules, A and B, in the asymmetric unit. In molecule A, the dihedral angles between the partly hydrogenated pyrimidine ring system (r.m.s. deviation = 0.056 Å and the sp2- and sp3-bonded phenyl groups are 33.32 (11 and 86.53 (11°, respectively. The equivalent data for molecule B are 0.049 Å, and 27.05 (10 and 85.27 (11°, respectively. In the crystal, A+B dimers linked by pairs of N—H...N hydrogen bonds generate R22(8 loops. The dimers are linked by aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.5367 (15 Å], which results in a three-dimensional network.

  3. Synthesis of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: potent and selective adenosine A3 receptor antagonists.

    Science.gov (United States)

    Banda, Veeraswamy; Chandrasekaran, Balakumar; Köse, Meryem; Vielmuth, Christin; Müller, Christa E; Chavva, Kurumurthy; Gautham, Santhosh Kumar; Pillalamarri, Sambasivarao; Mylavaram, Raghuprasad; Akkinepally, Raghuramarao; Pamulaparthy, Shanthanrao; Banda, Narsaiah

    2013-10-01

    A series of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 5 was prepared from 2-amino-3-cyano-4-trifluoromethyl-6-phenylpyridine 1 in two steps via formation of iminoether 3 followed by reaction with different aroylhydrazides 4. Representative products 5 were evaluated for their affinity towards all four subtypes of human adenosine receptors. Compounds 2-(3-fluorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5b), 2-(furan-2-yl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5d), and 2-(furan-2-yl)-5-methyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5j) showed high affinity for the A3 receptors, with Ki values of 8.1, 10.4, and 12.1 nM, respectively, and were >1000-fold selective versus all other adenosine receptor subtypes.

  4. Nucleobases and Prebiotic Molecules in Organic Residues Produced from the Ultraviolet Photo-Irradiation of Pyrimidine in NH3 and H2O+NH3 Ices

    Science.gov (United States)

    Nuevo, Michel; Milam, Stefanie N.; Sandford, Scott

    2012-01-01

    Although not yet identified in the interstellar medium (ISM), N-heterocycles including nucleobases the information subunits of DNA and RNA are present in carbonaceous chondrites, which indicates that molecules of biological interest can be formed in non-terrestrial environments via abiotic pathways. Recent laboratory experiments and ab-initio calculations have already shown that the irradiation of pyrimidine in pure H2O ices leads to the formation of a suite of oxidized pyrimidine derivatives, including the nucleobase uracil. In the present work, NH3:pyrimidine and H2O:NH3:pyrimidine ice mixtures with different relative proportions were irradiated with UV photons under astrophysically relevant conditions. Liquid- and gas-chromatography analysis of the resulting organic residues has led to the detection of the nucleobases uracil and cytosine, as well as other species of prebiotic interest such as urea and small amino acids. The presence of these molecules in organic residues formed under abiotic conditions supports scenarios in which extraterrestrial organics that formed in space and were subsequently delivered to telluric planets via comets and meteorites could have contributed to the inventory of molecules that triggered the first biological reactions on their surfaces.

  5. Adventures in Holographic Dimer Models

    Energy Technology Data Exchange (ETDEWEB)

    Kachru, Shamit; /Stanford U., Phys. Dept. /SLAC; Karch, Andreas; /Washington U., Seattle; Yaida, Sho; /Stanford U., Phys. Dept.

    2011-08-12

    We abstract the essential features of holographic dimer models, and develop several new applications of these models. Firstly, semi-holographically coupling free band fermions to holographic dimers, we uncover novel phase transitions between conventional Fermi liquids and non-Fermi liquids, accompanied by a change in the structure of the Fermi surface. Secondly, we make dimer vibrations propagate through the whole crystal by way of double trace deformations, obtaining nontrivial band structure. In a simple toy model, the topology of the band structure experiences an interesting reorganization as we vary the strength of the double trace deformations. Finally, we develop tools that would allow one to build, in a bottom-up fashion, a holographic avatar of the Hubbard model.

  6. A novel and convenient synthesis of thiazolo[3,2-a]pyrimidin-7-ones and pyrido[1,2-a]pyrimidin-2-ones using Vilsmeier reagent

    Institute of Scientific and Technical Information of China (English)

    Yi Yi Weng; Lei Ming Ying; Qi Xu Chen; Wei Ke Su

    2012-01-01

    A novel route for the synthesis of thiazolo[3,2-a]pyrimidin-7-ones and pyrido[1,2-a]pyrimidin-2-ones from acetylated 2-aminothiazoles and 2-aminopyridines under Vilsmeier conditions has been developed.The plausible mechanism has also been proposed.

  7. Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles.

    Science.gov (United States)

    Crow, Matthew J; Seekell, Kevin; Ostrander, Julie H; Wax, Adam

    2011-11-22

    The dimerization of receptors on the cell membrane is an important step in the activation of cell signaling pathways. Several methods exist for observing receptor dimerization, including coimmunoprecipitation, chemical cross-linking, and fluorescence resonance energy transfer (FRET). These techniques are limited in that only FRET is appropriate for live cells, but even that method suffers from photobleaching and bleed-through effects. In this study, we implement an alternative method for the targeting of HER-2 homodimer formation based on the plasmonic coupling of gold nanoparticles functionalized with HER-2 Ab. In the presented studies, SK-BR-3 cells, known to overexpress HER-2, are labeled with these nanoparticles and receptor colocalization is observed using plasmonic coupling. HER-2 targeted nanoparticles bound to these cells exhibit a peak resonance that is significantly red-shifted relative to those bound to similar receptors on A549 cells, which have significantly lower levels of HER-2 expression. This significant red shift indicates plasmonic coupling is occurring and points to a new avenue for assessing dimerization by monitoring their colocalization. To determine that dimerization is occurring, the refractive index of the nanoenvironment of the labels is assessed using a theoretical analysis based on the Mie coated sphere model. The results indicate scattering by single, isolated nanoparticles for the low HER-2 expressing A549 cell line, but the scattering observed for the HER-2 overexpressing SK-BR-3 cell line may only be explained by plasmonic-coupling of proximal nanoparticle pairs. To validate the conformation of nanoparticles bound to HER-2 receptors undergoing dimerization, discrete dipole approximation (DDA) models are used to assess spectra of scattering by coupled nanoparticles. Comparison of the experimental results with theoretical models indicates that NP dimers are formed for the labeling of SK-BR-3 cells, suggesting that receptor

  8. Dimerization in Highly Concentrated Solutions of Phosphoimidazolide Activated Monomucleotides

    Science.gov (United States)

    Kanavarioti, Anastassia

    1997-08-01

    Phosphoimidazolide activated ribomononucleotides (*pN) are useful substrates for the non-enzymatic synthesis of polynucleotides. However, dilute neutral aqueous solutions of *pN typically yield small amounts of dimers and traces of polymers; most of *pN hydrolyzes to yield nucleoside 5'-monophosphate. Here we report the self-condensation of nucleoside 5'-phosphate 2-methylimidazolide (2-MeImpN with N = cytidine, uridine or guanosine) in the presence of Mg2+ in concentrated solutions, such as might have been found in an evaporating lagoon on prebiotic Earth. The product distribution indicates that oligomerization is favored at the expense of hydrolysis. At 1.0 M, 2-MeImpU and 2-MeImpC produce about 65% of oligomers including 4% of the 3',5'-linked dimer. Examination of the product distribution of the three isomeric dimers in a self-condensation allows identification of reaction pathways that lead to dimer formation. Condensations in a concentrated mixture of all three nucleotides (U,C,G mixtures) is made possible by the enhanced solubility of 2-MeImpG in such mixtures. Although percent yield of internucleotide linked dimers is enhanced as a function of initial monomer concentration, pyrophosphate dimer yields remain practically unchanged at about 20% for 2-MeImpU, 16% for 2-MeImpC and 25% of the total pyrophosphate in the U,C,G mixtures. The efficiency by which oligomers are produced in these concentrated solutions makes the evaporating lagoon scenario a potentially interesting medium for the prebiotic synthesis of dimers and short RNAs.

  9. The Renaissance of Metal-Pyrimidine Nucleobase Coordination Chemistry.

    Science.gov (United States)

    Lippert, Bernhard; Sanz Miguel, Pablo J

    2016-08-16

    The significance of metal ions for the function and properties of DNA and RNA, long seen primarily under biological aspects and medicinal uses, has recently gained a renewed momentum. This is a consequence of the advent of novel applications in the fields of materials science, biotechnology, and analytical sensor chemistry that relate to the designed incorporation of transition metal ions into nucleic acid base pairs. Ag(+) and Hg(2+) ions, binding to pyrimidine (pym) nucleobases, represent major players in this development. Interestingly, these metal ions were the ones that some 60 years ago started the field! At the same time, the mentioned metal ions had demonstrated a "special relationship" with the pym nucleobases cytosine, thymine, and uracil! Parallel work conducted with oligonucleotides and model nucleobases fostered numerous significant details of these interactions, in particular when X-ray crystallography was involved, correcting earlier views occasionally. Our own activities during the past three to four decades have focused on, among others, the coordination chemistry of transition and main-group metal ions with pym model nucleobases, with an emphasis on Pt(II) and Pd(II). It has always been our goal to deduce, if possible, the potential relevance of our findings for biological processes. It is interesting to put our data, in particular for trans-a2Pt(II) (a = NH3 or amine), into perspective with those of other metal ions, notably Ag(+) and Hg(2+). Irrespective of major differences in kinetics and lability/inertness between d(8) and d(10) metal ions, there is also a lot of similarity in structural aspects as a result of the preferred linear coordination geometry of these species. Moreover, the apparent clustering of metal ions to the pym nucleobases, which is presumably essential for the formation of nanoclusters on oligonucleotide scaffolds, is impressively reflected in model systems, as are reasons for inter-nucleobase cross-links containing more

  10. Novel pyrimidine-2,4-dione-1,2,3-triazole and furo[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation.

    Science.gov (United States)

    Gregorić, Tomislav; Sedić, Mirela; Grbčić, Petra; Tomljenović Paravić, Andrea; Kraljević Pavelić, Sandra; Cetina, Mario; Vianello, Robert; Raić-Malić, Silvana

    2017-01-05

    Regioselective 1,4-disubstituted 1,2,3-triazole tethered pyrimidine-2,4-dione derivatives (5-23) were successfully prepared by the copper(I)-catalyzed click chemistry. While known palladium/copper-cocatalyzed method based on Sonogashira cross-coupling followed by the intramolecular 5-endo-dig ring closure generated novel 6-alkylfuro[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids (24b-37b), a small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and described for the first time by tandem terminal alkyne dimerization and subsequent 5-endo-trig cyclization, which was additionally corroborated with computational and X-ray crystal structure analyses. The nature of substituents on alkynes and thereof homocoupled 1,3-diynes predominantly influenced the ratio of the formed products in both pathways. In vitro antiproliferative activity of prepared compounds evaluated on five human cancer cell lines revealed that N,N-1,3-bis-(1,2,3-triazole)-5-bromouracil (5-7) and 5,6-disubstituted furo[2,3-d]pyrimidine-2-one-1,2,3-triazole 34a hybrids exhibited the most pronounced cytostatic acitivities against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cells with higher potencies than the reference drug 5-fluorouracil. Cytostatic effect of pyrimidine-2,4-dione-1,2,3-triazole hybrid 7 in HepG2 cells could be attributed to the Wee-1 kinase inhibition and abolishment of sphingolipid signaling mediated by acid ceramidase and sphingosine kinase 1. Importantly, this compound proved to be a non-mitochondrial toxicant, which makes it a promising candidate for further lead optimization and development of a new and more efficient agent for the treatment of hepatocellular carcinoma.

  11. Self-deactivation of water vapor - Role of the dimer

    Science.gov (United States)

    Zuckerwar, A. J.

    1984-01-01

    A phenomenological multiple-relaxation theory of the deactivation rate constant for the nu-2 (1 - 0) bending mode of water vapor is presented which incorporates the role not only of the excited monomer but also of the bound molecular complex, in particular the dimer. The deactivation takes place by means of three parallel processes: (1) collisional deexcitation of the excited monomer, (2) a two-step reaction involving association and spontaneous redissociation of an H2O collision complex, and (3) spontaneous dissociation of the stably bound H2O dimer. Oxygen, but not nitrogen or argon, serves as an effective chaperon for the formation of the activated complex. This observation explains the impurity dependence of the self-deactivation rate constant of water vapor. Analysis of an ultrasonic absorption peak based on the third process yields values for the standard entropy and enthalpy of dissociation of the stably bound H2O dimer.

  12. Characterization of oxygen dimer-enriched silicon detectors

    CERN Document Server

    Boisvert, V; Moll, M; Murin, L I; Pintilie, I

    2005-01-01

    Various types of silicon material and silicon p+n diodes have been treated to increase the concentration of the oxygen dimer (O2i) defect. This was done by exposing the bulk material and the diodes to 6 MeV electrons at a temperature of about 350 °C. FTIR spectroscopy has been performed on the processed material confirming the formation of oxygen dimer defects in Czochralski silicon pieces. We also show results from TSC characterization on processed diodes. Finally, we investigated the influence of the dimer enrichment process on the depletion voltage of silicon diodes and performed 24 GeV/c proton irradiations to study the evolution of the macroscopic diode characteristics as a function of fluence.

  13. Cooperative binding mode of the inhibitors of R6K replication, pi dimers.

    Science.gov (United States)

    Bowers, Lisa M; Filutowicz, Marcin

    2008-03-28

    The replication initiator protein, pi, plays an essential role in the initiation of plasmid R6K replication. Both monomers and dimers of pi bind to iterons in the gamma origin of plasmid R6K, yet monomers facilitate open complex formation, while dimers, the predominant form in the cell, do not. Consequently, pi monomers activate replication, while pi dimers inhibit replication. Recently, it was shown that the monomeric form of pi binds multiple tandem iterons in a strongly cooperative fashion, which might explain how monomers outcompete dimers for replication initiation when plasmid copy number and pi supply are low. Here, we examine cooperative binding of pi dimers and explore the role that these interactions may have in the inactivation of gamma origin. To examine pi dimer/iteron interactions in the absence of competing pi monomer/iteron interactions using wild-type pi, constructs were made with key base changes to each iteron that eliminate pi monomer binding yet have no impact on pi dimer binding. Our results indicate that, in the absence of pi monomers, pi dimers bind with greater cooperativity to alternate iterons than to adjacent iterons, thus preferentially leaving intervening iterons unbound and the origin unsaturated. We discuss new insights into plasmid replication control by pi dimers.

  14. The EGF repeat-specific O-GlcNAc-transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila.

    Directory of Open Access Journals (Sweden)

    Reto Müller

    Full Text Available The O-GlcNAc transferase Eogt modifies EGF repeats in proteins that transit the secretory pathway, including Dumpy and Notch. In this paper, we show that the Notch ligands Delta and Serrate are also substrates of Eogt, that mutation of a putative UDP-GlcNAc binding DXD motif greatly reduces enzyme activity, and that Eogt and the cytoplasmic O-GlcNAc transferase Ogt have distinct substrates in Drosophila larvae. Loss of Eogt is larval lethal and disrupts Dumpy functions, but does not obviously perturb Notch signaling. To identify novel genetic interactions with eogt, we investigated dominant modification of wing blister formation caused by knock-down of eogt. Unexpectedly, heterozygosity for several members of the canonical Notch signaling pathway suppressed wing blister formation. And importantly, extensive genetic interactions with mutants in pyrimidine metabolism were identified. Removal of pyrimidine synthesis alleles suppressed wing blister formation, while removal of uracil catabolism alleles was synthetic lethal with eogt knock-down. Therefore, Eogt may regulate protein functions by O-GlcNAc modification of their EGF repeats, and cellular metabolism by affecting pyrimidine synthesis and catabolism. We propose that eogt knock-down in the wing leads to metabolic and signaling perturbations that increase cytosolic uracil levels, thereby causing wing blister formation.

  15. Tetraoxane-pyrimidine nitrile hybrids as dual stage antimalarials.

    Science.gov (United States)

    Oliveira, Rudi; Guedes, Rita C; Meireles, Patrícia; Albuquerque, Inês S; Gonçalves, Lídia M; Pires, Elisabete; Bronze, Maria Rosário; Gut, Jiri; Rosenthal, Philip J; Prudêncio, Miguel; Moreira, Rui; O'Neill, Paul M; Lopes, Francisca

    2014-06-12

    The use of artemisinin or other endoperoxides in combination with other drugs is a strategy to prevent development of resistant strains of Plasmodium parasites. Our previous work demonstrated that hybrid compounds, comprising endoperoxides and vinyl sulfones, were capable of high activity profiles comparable to artemisinin and chloroquine while acting through two distinct mechanisms of action: oxidative stress and falcipain inhibition. In this study, we adapted this approach to a novel class of falcipain inhibitors: peptidomimetic pyrimidine nitriles. Pyrimidine tetraoxane hybrids displayed potent nanomolar activity against three strains of Plasmodium falciparum and falcipain-2, combined with low cytotoxicity. In vivo, a decrease in parasitemia and an increase in survival of mice infected with Plasmodium berghei was observed when compared to control. All tested compounds combined good blood stage activity with significant effects on liver stage parasitemia, a most welcome feature for any new class of antimalarial drug.

  16. 5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors.

    Science.gov (United States)

    Arasappan, Ashok; Bennett, Frank; Girijavallabhan, Vinay; Huang, Yuhua; Huelgas, Regina; Alvarez, Carmen; Chen, Lei; Gavalas, Stephen; Kim, Seong-Heon; Kosinski, Aneta; Pinto, Patrick; Rizvi, Razia; Rossman, Randall; Shankar, Bandarpalle; Tong, Ling; Velazquez, Francisco; Venkatraman, Srikanth; Verma, Vishal A; Kozlowski, Joseph; Shih, Neng-Yang; Piwinski, John J; MacCoss, Malcolm; Kwong, Cecil D; Clark, Jeremy L; Fowler, Anita T; Geng, Feng; Kezar, Hollis S; Roychowdhury, Abhijit; Reynolds, Robert C; Maddry, Joseph A; Ananthan, Subramaniam; Secrist, John A; Li, Cheng; Chase, Robert; Curry, Stephanie; Huang, Hsueh-Cheng; Tong, Xiao; Njoroge, F George

    2012-05-01

    Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol.

  17. Pyrimidine Nucleobase Radical Reactivity in DNA and RNA.

    Science.gov (United States)

    Greenberg, Marc M

    2016-11-01

    Nucleobase radicals are major products of the reactions between nucleic acids and hydroxyl radical, which is produced via the indirect effect of ionizing radiation. The nucleobase radicals also result from hydration of cation radicals that are produced via the direct effect of ionizing radiation. The role that nucleobase radicals play in strand scission has been investigated indirectly using ionizing radiation to generate them. More recently, the reactivity of nucleobase radicals resulting from formal hydrogen atom or hydroxyl radical addition to pyrimidines has been studied by independently generating the reactive intermediates via UV-photolysis of synthetic precursors. This approach has provided control over where the reactive intermediates are produced within biopolymers and facilitated studying their reactivity. The contributions to our understanding of pyrimidine nucleobase radical reactivity by this approach are summarized.

  18. Pyrimidine nucleobase radical reactivity in DNA and RNA

    Science.gov (United States)

    Greenberg, Marc M.

    2016-11-01

    Nucleobase radicals are major products of the reactions between nucleic acids and hydroxyl radical, which is produced via the indirect effect of ionizing radiation. The nucleobase radicals also result from hydration of cation radicals that are produced via the direct effect of ionizing radiation. The role that nucleobase radicals play in strand scission has been investigated indirectly using ionizing radiation to generate them. More recently, the reactivity of nucleobase radicals resulting from formal hydrogen atom or hydroxyl radical addition to pyrimidines has been studied by independently generating the reactive intermediates via UV-photolysis of synthetic precursors. This approach has provided control over where the reactive intermediates are produced within biopolymers and facilitated studying their reactivity. The contributions to our understanding of pyrimidine nucleobase radical reactivity by this approach are summarized.

  19. Elements located upstream and downstream of the major splice donor site influence the ability of HIV-2 leader RNA to dimerize in vitro.

    Science.gov (United States)

    Lanchy, Jean-Marc; Rentz, Casey A; Ivanovitch, John D; Lodmell, J Stephen

    2003-03-11

    An essential step in the replication cycle of all retroviruses is the dimerization of genomic RNA prior to or during budding and maturation of the viral particle. In HIV-1, a 5' leader region site termed stem-loop 1 (SL1) promotes RNA dimerization in vitro and influences dimerization in vivo. In HIV-2, two sequences promote dimerization of RNA fragments in vitro: the 5'-end of the primer-binding site (PBS) and a stem-loop region homologous to the HIV-1 SL1 sequence. Because HIV-2 RNA constructs of different lengths use these two dimerization signals disproportionately, we hypothesized that other sequences could modulate their relative utilization. Here, we characterized the influence of sequences upstream and downstream of the major splice donor site on the formation of HIV-2 RNA dimers in vitro using a variety of RNA constructs and dimerization and electrophoresis protocols. We first assayed the formation of loose or tight dimers for 1-444 and 1-561 model RNAs. Although both RNAs could form PBS-dependent loose dimers, the 1-561 RNA was unable to make SL1-dependent tight dimers. Using RNAs truncated at their 5'- and/or 3'-ends and by making compensatory base substitutions, we found that two elements interfere with the formation of SL1-dependent tight dimers. The cores of these elements are located at nucleotides 189-196 and 543-550. Our results suggest that base pairing between these sequences prevents the formation of SL1-dependent tight dimers, probably by sequestering SL1 in a stable intramolecular arrangement. Moreover, we found that nucleotides downstream of SL1 decreased the rate of tight dimerization. Interestingly, dimerization at 37 degrees C in the presence of nucleocapsid protein increased the yield of SL1-mediated tight dimerization in vitro, even in the presence of the two interfering elements, suggesting a relationship between the nucleocapsid protein and activation of the SL1 dimerization signal in vivo.

  20. Structural basis for sequence specific DNA binding and protein dimerization of HOXA13.

    Directory of Open Access Journals (Sweden)

    Yonghong Zhang

    Full Text Available The homeobox gene (HOXA13 codes for a transcription factor protein that binds to AT-rich DNA sequences and controls expression of genes during embryonic morphogenesis. Here we present the NMR structure of HOXA13 homeodomain (A13DBD bound to an 11-mer DNA duplex. A13DBD forms a dimer that binds to DNA with a dissociation constant of 7.5 nM. The A13DBD/DNA complex has a molar mass of 35 kDa consistent with two molecules of DNA bound at both ends of the A13DBD dimer. A13DBD contains an N-terminal arm (residues 324 - 329 that binds in the DNA minor groove, and a C-terminal helix (residues 362 - 382 that contacts the ATAA nucleotide sequence in the major groove. The N370 side-chain forms hydrogen bonds with the purine base of A5* (base paired with T5. Side-chain methyl groups of V373 form hydrophobic contacts with the pyrimidine methyl groups of T5, T6* and T7*, responsible for recognition of TAA in the DNA core. I366 makes similar methyl contacts with T3* and T4*. Mutants (I366A, N370A and V373G all have decreased DNA binding and transcriptional activity. Exposed protein residues (R337, K343, and F344 make intermolecular contacts at the protein dimer interface. The mutation F344A weakens protein dimerization and lowers transcriptional activity by 76%. We conclude that the non-conserved residue, V373 is critical for structurally recognizing TAA in the major groove, and that HOXA13 dimerization is required to activate transcription of target genes.

  1. Synthesis and biological evaluation of some New pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Firyal Weli Askar

    2017-06-01

    Full Text Available New pyrimidine derivatives comprising azo, schiff's bases, chalcones, and chromene ring moieties were prepared.The newly synthesized compounds have been established on the basis of their m.p., TLC, FT-IR, UV-Vis ,¹H-NMR data and element analysis. These compounds were screened for their antimicrobial and in vitro antioxidant properties. The results of this investigation revealed that these compounds are potent antimicrobial and antioxidant agent.

  2. Synthesis and Antibacterial Activity of Chalcones and Pyrimidine-2-ones

    OpenAIRE

    2005-01-01

    Some new chalcones have been prepared by Claisen-schmidt condensation of ketone and different aromatic aldehydes. These chalcones on condensation with urea in presence of acid gave Pyrimidine-2-ones. The synthesized compounds have been characterized by elemental analysis, IR and 1H NMR spectral data. They have been screened for their antibacterial activity against Gram positive bacteria B. subtillis & S. aureus and Gram negative bacteria E. coli & S. typhi.

  3. Kinetics of DNA tile dimerization.

    Science.gov (United States)

    Jiang, Shuoxing; Yan, Hao; Liu, Yan

    2014-06-24

    Investigating how individual molecular components interact with one another within DNA nanoarchitectures, both in terms of their spatial and temporal interactions, is fundamentally important for a better understanding of their physical behaviors. This will provide researchers with valuable insight for designing more complex higher-order structures that can be assembled more efficiently. In this report, we examined several spatial factors that affect the kinetics of bivalent, double-helical (DH) tile dimerization, including the orientation and number of sticky ends (SEs), the flexibility of the double helical domains, and the size of the tiles. The rate constants we obtained confirm our hypothesis that increased nucleation opportunities and well-aligned SEs accelerate tile-tile dimerization. Increased flexibility in the tiles causes slower dimerization rates, an effect that can be reversed by introducing restrictions to the tile flexibility. The higher dimerization rates of more rigid tiles results from the opposing effects of higher activation energies and higher pre-exponential factors from the Arrhenius equation, where the pre-exponential factor dominates. We believe that the results presented here will assist in improved implementation of DNA tile based algorithmic self-assembly, DNA based molecular robotics, and other specific nucleic acid systems, and will provide guidance to design and assembly processes to improve overall yield and efficiency.

  4. Spectral and photophysical studies of inclusion complexes of 2-amino-4,6-dimethyl pyrimidine with beta-cyclodextrin.

    Science.gov (United States)

    El-Kemary, M A; El-Gezawy, H S; El-Baradie, H Y; Issa, R M

    2002-02-01

    The interaction of 2-amino-4,6-dimethyl pyrimidine (ADMP) with beta-cyclodextrin (beta-CD) has been studied by means of UV absorption, steady state and time resolved fluorescence techniques. Spectral characteristics, bandwidths and photophysical parameters indicating that ADMP experience two different environments in aqueous solutions: bulk water and 1:1 (ADMP:beta-CD) inclusion complexation. The size restriction of the upper rim of beta-CD partially include ADMP and prevent the possibility of formation of 1:2 complex. The effective polarity of the cyclodextrin cavity experienced by the induced ADMP is equivalent with the polarity of an 80:20 methanol-water mixture.

  5. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    DEFF Research Database (Denmark)

    Ussery, David; Bohlin, J; Hardy, SP

    2009-01-01

    -tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p factors......BACKGROUND: The genomic fractions of purine (RR) and alternating pyrimidine/purine (YR) stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors...... regression analysis to investigate how AT content, habitat, growth temperature, pathogenicity, phyla, oxygen requirement and halotolerance correlated with the distribution of RR and YR stretches in prokaryotes. RESULTS: Our results indicate that RR and YR-stretches are differently distributed in prokaryotic...

  6. NMR Structural Studies on Alamethicin Dimers

    Institute of Scientific and Technical Information of China (English)

    李星

    2003-01-01

    15N labeled alamethicin dimer was synthesized. The structure and dynamics of alamethicin dimers were studied with nuclear magnetic resonance (NMR) spectroscopy. The data from 15N-labeled alamethicin dimer suggest little differences in conformation between the dimer and monomer in the Aib1-Pro14 region. Significant difference in the conformation of the C-terminus are manifest in the NH chemical shifts in the Val15-Pho20 region.

  7. Synthesis and Applications of Non-spherical Dimer Colloids

    Science.gov (United States)

    Yoon, Kisun

    Colloids are promising building blocks in material synthesis because of their controllability of size and surface properties. The synthesis of chemically and/or geometrically anisotropic colloidal particles has received attentions with the expectation of building blocks for complex structures. However, the synthesis of anisotropic colloidal particles is by far more difficult than the synthesis of spherical colloidal particles. Lack of monodispersity and productivity of many anisotropic particles often limits their applications as a building block for complex structures. Thus, it is highly desirable to develop methods which can produce a large amount of monodisperse non-spherical particles with controllable asymmetric surface properties. This dissertation details the work for developing such a method. The major result of this dissertation is a synthetic method to produce monodisperse non-spherical colloids with anisotropic surface property in a large quantity. The anisotropic colloid, which we call it as Dimer particle, has two fused lobes like a dumbbell and each lobe's size can be independently controlled. We present a novel method to synthesize sub-micron size Dimer particles. This method can produce a large amount of submicron-sized Dimer particles with good monodispersity and well-controlled shape. Submicron-sized Dimer particles have been highly desired since they can be used as a building block for self assembly using Brownian motion, colloidal surfactant for Pickering emulsion, and photonic materials. To fully take advantage of the anisotropy of the particles, we develop a facile method to tailor the surface property of each lobe independently by asymmetrically coating the particles with gold nanoparticles. This method doesn't need the arrangement of particles onto any type of interfaces. Asymmetric coating of gold nanoparticles can be carried out simply by mixing Dimer particles with gold nanoparticles. The formation mechanism of the submicron-sized Dimer

  8. Micellisation and immunoreactivities of dimeric beta-caseins.

    Science.gov (United States)

    Yousefi, Reza; Gaudin, Jean-Charles; Chobert, Jean-Marc; Pourpak, Zahra; Moin, Mostafa; Moosavi-Movahedi, Ali Akbar; Haertle, Thomas

    2009-12-01

    Bovine beta-casein (beta-CN) is a highly amphiphilic micellising phospho-protein showing chaperone-like activity in vitro. Recently, existence of multiple sequential epitopes on beta-CN polypeptide chain in both hydrophilic-polar (psi) and hydrophobic-apolar domains (phi) has been evidenced. In order to clarify specific contribution of polar and apolar domains in micellisation process and in shaping immunoreactivity of beta-CN, its dimeric/bi-amphiphilic "quasi palindromic" forms covalently connected by a disulfide bond linking either N-terminal (C4 beta-CND) or C-terminal domain (C208 beta-CND) were produced and studied. Depending on the C- or N-terminal position of inserted cysteine, each dimeric beta-CN contains one polar/apolar region at the centre and two external hydrophobic/hydrophilic ends. Consequently, such casein dimers have radically different polarities/hydrophobicities on their outside surfaces. Dynamic light scattering (DLS) measurements indicate that these dimeric casein molecules form micelles of different sizes depending on arrangement of polar fragments of the beta-CN mutants in their constrained dimers. Non-aggregated dimers have different hydrodynamic diameters that could be explained by their different geometries. Measurements of fluorescence showed more hydrophobic environment of Trp residues of C208 beta-CND, while in similar experimental conditions Trp residues of C4 beta-CND and native beta-CN were more exposed to the polar medium. Both fluorescence and DLS studies showed greater propensity for micellisation of the dimeric beta-CNs, suggesting that the factors inducing the formation of micelles are stronger in the bi-amphiphilic dimers. 1-anilino-naphthalene-8-sulfonate (ANS) binding studies showed different binding of ANS by these dimers as well as different exposition of ANS binding (hydrophobic) regions in the micellar states. The differences in fluorescence resonance energy transfer (FRET) profiles of C4 beta-CND and C208 beta-CND can

  9. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich

    2012-03-01

    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  10. Rubidium dimers in paraffin-coated cells

    CERN Document Server

    Acosta, V M; Windes, D; Corsini, E; Ledbetter, M P; Karaulanov, T; Auzinsh, M; Rangwala, S A; Kimball, D F Jackson; Budker, D

    2010-01-01

    Measurements were made to determine the density of rubidium dimer vapor in paraffin-coated cells. The number density of dimers and atoms in similar paraffin-coated and uncoated cells was measured by optical spectroscopy. Due to the relatively low melting point of paraffin, a limited temperature range of 43-80 deg C was explored, with the lower end corresponding to a dimer density of less than 10^7 cm^(-3). With one-minute integration time, a sensitivity to dimer number density of better than 10^6 cm^(-3) was achieved. No significant difference in dimer density was observed between the cells.

  11. Antimicrobial peptide protegrin-3 adopt an antiparallel dimer in the presence of DPC micelles: a high-resolution NMR study

    Energy Technology Data Exchange (ETDEWEB)

    Usachev, K. S., E-mail: k.usachev@kpfu.ru; Efimov, S. V.; Kolosova, O. A.; Klochkova, E. A.; Aganov, A. V.; Klochkov, V. V. [Kazan Federal University, NMR Laboratory, Institute of Physics (Russian Federation)

    2015-05-15

    A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel β-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric β-barrels.

  12. An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

    Indian Academy of Sciences (India)

    SOMESHWAR DESHMUKH; KUNAL DINGORE; VISHWAS GAIKWAD; MADHUKAR JACHAK

    2016-09-01

    A series of new pyrazolo[1,5-a]pyrimidine derivatives has been synthesized by using 7-hydrazinyl- 5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 1 and 7-amino-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 2 as precursors. The pyrazolo[3,4-d] pyrimidines 3a–b have been synthesized by a three-step reactionstarting with 1. Compound 1 was utilized for the synthesis of dioxopyrrolidindolinylamio-pyrazolo-pyrimidines 4a–b, and dioxoisoindolin-pyrazolo-pyrimidines 4c–d. Also, compounds 4a-d were synthesized using deepeutectic solvents (DES). This method using DES provides several advantages such as benign environment, high yield, scalable and simple work-up procedure. Similarly, the cyclocondensation of 2 with α-acetyl- γ -butyrolactone afforded pyrazolo-pyrido-pyrimidine 5 and dihydrofuro-pyrido-pyrazolo-pyrimidine 6. All synthesized compounds were screened for antimicrobial activity.

  13. Fiber optic D dimer biosensor

    Science.gov (United States)

    Glass, Robert S.; Grant, Sheila A.

    1999-01-01

    A fiber optic sensor for D dimer (a fibrinolytic product) can be used in vivo (e.g., in catheter-based procedures) for the diagnosis and treatment of stroke-related conditions in humans. Stroke is the third leading cause of death in the United States. It has been estimated that strokes and stroke-related disorders cost Americans between $15-30 billion annually. Relatively recently, new medical procedures have been developed for the treatment of stroke. These endovascular procedures rely upon the use of microcatheters. These procedures could be facilitated with this sensor for D dimer integrated with a microcatheter for the diagnosis of clot type, and as an indicator of the effectiveness, or end-point of thrombolytic therapy.

  14. Mechanism of FGF receptor dimerization and activation

    Science.gov (United States)

    Sarabipour, Sarvenaz; Hristova, Kalina

    2016-01-01

    Fibroblast growth factors (fgfs) are widely believed to activate their receptors by mediating receptor dimerization. Here we show, however, that the FGF receptors form dimers in the absence of ligand, and that these unliganded dimers are phosphorylated. We further show that ligand binding triggers structural changes in the FGFR dimers, which increase FGFR phosphorylation. The observed effects due to the ligands fgf1 and fgf2 are very different. The fgf2-bound dimer structure ensures the smallest separation between the transmembrane (TM) domains and the highest possible phosphorylation, a conclusion that is supported by a strong correlation between TM helix separation in the dimer and kinase phosphorylation. The pathogenic A391E mutation in FGFR3 TM domain emulates the action of fgf2, trapping the FGFR3 dimer in its most active state. This study establishes the existence of multiple active ligand-bound states, and uncovers a novel molecular mechanism through which FGFR-linked pathologies can arise.

  15. DNA repair mechanism by photolyase: electron transfer path from the photolyase catalytic cofactor FADH(-) to DNA thymine dimer.

    Science.gov (United States)

    Medvedev, D; Stuchebrukhov, A A

    2001-05-21

    Photolyase is an enzyme that catalyses photorepair of thymine dimers in UV damaged DNA by electron transfer reaction. The structure of the photolyase/DNA complex is unknown at present. Using crystal structure coordinates of the substrate-free enzyme from E. coli, we have recently built a computer molecular model of a thymine dimer docked to photolyase catalytic site and studied molecular dynamics of the system. In this paper, we present analysis of the electronic coupling and electron transfer pathway between the catalytic cofactor FADH(-) and the pyrimidine dimer by the method of interatomic tunneling currents. Electronic structure is treated in the extended Hückel approximation. The root mean square transfer matrix element is about 6 cm(-1), which is consistent with the experimentally determined rate of transfer. We find that electron transfer mechanism responsible for the repair utilizes an unusual folded conformation of FADH(-) in photolyases, in which the isoalloxazine ring of the flavin and the adenine are in close proximity, and the peculiar features of the docked orientation of the dimer. The tunneling currents show explicitly that despite of the close proximity between the donor and acceptor complexes, the electron transfer mechanism between the flavin and the thymine bases is not direct, but indirect, with the adenine acting as an intermediate. These calculations confirm the previously made conclusion based on an indirect evidence for such mechanism.

  16. Kinetics of cyclobutane thymine dimer splitting by DNA photolyase directly monitored in the UV.

    Science.gov (United States)

    Thiagarajan, Viruthachalam; Byrdin, Martin; Eker, André P M; Müller, Pavel; Brettel, Klaus

    2011-06-07

    CPD photolyase uses light to repair cyclobutane pyrimidine dimers (CPDs) formed between adjacent pyrimidines in UV-irradiated DNA. The enzyme harbors an FAD cofactor in fully reduced state (FADH(-)). The CPD repair mechanism involves electron transfer from photoexcited FADH(-) to the CPD, splitting of its intradimer bonds, and electron return to restore catalytically active FADH(-). The two electron transfer processes occur on time scales of 10(-10) and 10(-9) s, respectively. Until now, CPD splitting itself has only been poorly characterized by experiments. Using a previously unreported transient absorption setup, we succeeded in monitoring cyclobutane thymine dimer repair in the main UV absorption band of intact thymine at 266 nm. Flavin transitions that overlay DNA-based absorption changes at 266 nm were monitored independently in the visible and subtracted to obtain the true repair kinetics. Restoration of intact thymine showed a short lag and a biexponential rise with time constants of 0.2 and 1.5 ns. We assign these two time constants to splitting of the intradimer bonds (creating one intact thymine and one thymine anion radical T(∘-)) and electron return from T(∘-) to the FAD cofactor with recovery of the second thymine, respectively. Previous model studies and computer simulations yielded various CPD splitting times between < 1 ps and < 100 ns. Our experimental results should serve as a benchmark for future efforts to model enzymatic photorepair. The technique and methods developed here may be applied to monitor other photoreactions involving DNA.

  17. A Model for Dimerization of the SOX Group E Transcription Factor Family.

    Science.gov (United States)

    Ramsook, Sarah N; Ni, Joyce; Shahangian, Shokofeh; Vakiloroayaei, Ana; Khan, Naveen; Kwan, Jamie J; Donaldson, Logan W

    2016-01-01

    Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG) domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

  18. Evidence for the dimerization-mediated catalysis of methionine sulfoxide reductase A from Clostridium oremlandii.

    Science.gov (United States)

    Lee, Eun Hye; Lee, Kitaik; Kwak, Geun-Hee; Park, Yeon Seung; Lee, Kong-Joo; Hwang, Kwang Yeon; Kim, Hwa-Young

    2015-01-01

    Clostridium oremlandii MsrA (CoMsrA) is a natively selenocysteine-containing methionine-S-sulfoxide reductase and classified into a 1-Cys type MsrA. CoMsrA exists as a monomer in solution. Herein, we report evidence that CoMsrA can undergo homodimerization during catalysis. The monomeric CoMsrA dimerizes in the presence of its substrate methionine sulfoxide via an intermolecular disulfide bond between catalytic Cys16 residues. The dimeric CoMsrA is resolved by the reductant glutaredoxin, suggesting the relevance of dimerization in catalysis. The dimerization reaction occurs in a concentration- and time-dependent manner. In addition, the occurrence of homodimer formation in the native selenoprotein CoMsrA is confirmed. We also determine the crystal structure of the dimeric CoMsrA, having the dimer interface around the two catalytic Cys16 residues. A central cone-shaped hole is present in the surface model of dimeric structure, and the two Cys16 residues constitute the base of the hole. Collectively, our biochemical and structural analyses suggest a novel dimerization-mediated mechanism for CoMsrA catalysis that is additionally involved in CoMsrA regeneration by glutaredoxin.

  19. Synchronized oscillations of dimers in biphasic charged fd-virus suspensions

    Science.gov (United States)

    Kang, K.; Piao, S. H.; Choi, H. J.

    2016-08-01

    Micron-sized colloidal spheres that are dispersed in an isotropic-nematic biphasic host suspension of charged rods (fd-virus particles) are shown to spontaneously form dimers, which exhibit a synchronized oscillatory motion. Dimer formation is not observed in the monophase of isotropic and nematic suspensions. The synchronized oscillations of dimers are connected to the inhomogeneous state of the host suspension of charged rods (fd viruses) where nematic domains are in coexistence with isotropic regions. The synchronization of oscillations occurs in bulk states, in the absence of an external field. With a low field strength of an applied electric field, the synchronization is rather reduced, but it recovers again when the field is turned off. In this Rapid Communication, we report this observation as an example of the strange attractor, occurring in the mixture of PS (polystyrene) dimers in an isotropic-nematic coexistence biphasic fd-virus network. Furthermore, we highlight that the synchronization of PS-dimer oscillations is the result of a global bifurcation diagram, driven by a delicate balance between the short-attractive "twisted" interaction of PS dimers and long-ranged electrostatic repulsive interactions of charged fd rods. The interest is then in the local enhancement of "twist-nematic" elasticity in reorientation of the dimer oscillations. An analysis of image-time correlations is provided with the data movies and Fourier transforms of averaged orientations for the synchronized oscillations of dimers in the biphasic I -N coexistence concentration of charged fd-virus suspensions.

  20. Fourier transform infrared spectroscopy and theoretical study of dimethylamine dimer in the gas phase.

    Science.gov (United States)

    Du, Lin; Kjaergaard, Henrik G

    2011-11-10

    Dimethylamine (DMA) has been studied by gas-phase Fourier transform infrared (FTIR) spectroscopy. We have identified a spectral transition that is assigned to the DMA dimer. The IR spectra of the dimer in the gas phase are obtained by spectral subtraction of spectra recorded at different pressures. The enthalpy of hydrogen bond formation was obtained for the DMA dimer by temperature-dependence measurements. We complement the experimental results with ab initio and anharmonic local mode model calculations of monomer and dimer. Compared to the monomer, our calculations show that in the dimer the N-H bond is elongated, and the NH-stretching fundamental shifts to a lower wavenumber. More importantly, the weak NH-stretching fundamental transition has a pronounced intensity increase upon complexation. However, the first NH-stretching overtone transition is not favored by the same intensity enhancement, and we do not observe the first NH-stretching overtone of the dimer. On the basis of the measured and calculated intensity of the NH-stretching transition of the dimer, the equilibrium constant for dimerization at room temperature was determined.

  1. Palladium-catalyzed regioselective arylation of imidazo[1,2-a]pyrimidine.

    Science.gov (United States)

    Li, Wenjie; Nelson, Dorian P; Jensen, Mark S; Hoerrner, R Scott; Javadi, Gary J; Cai, Dongwei; Larsen, Robert D

    2003-12-11

    Imidazo[1,2-a]pyrimidine can be arylated at the 3-position with aryl bromides in the presence of base and a catalytic amount of palladium. This provides an efficient one-step synthesis of 3-arylimidazo[1,2-a]pyrimidines from the unsubstituted heterocycle. [reaction: see text

  2. Carbon-Carbon Bond Cleavage Reaction: Synthesis of Multisubstituted Pyrazolo[1,5-a]pyrimidines.

    Science.gov (United States)

    Saikia, Pallabi; Gogoi, Sanjib; Boruah, Romesh C

    2015-07-02

    A new carbon-carbon bond cleavage reaction was developed for the efficient synthesis of multisubstituted pyrazolo[1,5-a]pyrimidines. This base induced reaction of 1,3,5-trisubstituted pentane-1,5-diones and substituted pyrazoles afforded good yields of the pyrazolo[1,5-a]pyrimidines.

  3. Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain

    Directory of Open Access Journals (Sweden)

    Cowburn David

    2011-05-01

    Full Text Available Abstract Background The C-terminal domain (CTD of HIV-1 capsid (CA, like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs. Results Due to the pivotal role of the dimer interface, we reasoned that peptides from the α-helical region of the dimer interface might be effective as decoys to prevent CTD dimer formation. However, these small peptides do not have any structure in solution and they do not penetrate cells. Therefore, we used the hydrocarbon stapling technique to stabilize the α-helical structure and confirmed by confocal microscopy that this modification also made these peptides cell-penetrating. We also confirmed by using isothermal titration calorimetry (ITC, sedimentation equilibrium and NMR that these peptides indeed disrupt dimer formation. In in vitro assembly assays, the peptides inhibited mature-like virus particle formation and specifically inhibited HIV-1 production in cell-based assays. These peptides also showed potent antiviral activity against a large panel of laboratory-adapted and primary isolates, including viral strains resistant to inhibitors of reverse transcriptase and protease. Conclusions These preliminary data serve as the foundation for designing small, stable, α-helical peptides and small-molecule inhibitors targeted against the CTD dimer interface. The observation that relatively weak CA binders, such as NYAD-201 and NYAD-202, showed specificity and are able to disrupt the CTD dimer is encouraging for further exploration of a much broader class of antiviral compounds targeting CA. We cannot exclude the possibility that the CA-based peptides described here could elicit additional effects on virus replication not directly linked to their ability to bind

  4. Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

    NARCIS (Netherlands)

    Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.

    2001-01-01

    The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals

  5. Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

    NARCIS (Netherlands)

    Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.

    2001-01-01

    The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals synthes

  6. Wave packet dynamics of potassium dimers attached to helium nanodroplets

    OpenAIRE

    Claas, P.; Droppelmann, G.; Schulz, C. P.; Mudrich, M.; Stienkemeier, F.

    2006-01-01

    The dynamics of vibrational wave packets excited in K$_2$ dimers attached to superfluid helium nanodroplets is investigated by means of femtosecond pump-probe spectroscopy. The employed resonant three-photon-ionization scheme is studied in a wide wavelength range and different pathways leading to K$^+_2$-formation are identified. While the wave packet dynamics of the electronic ground state is not influenced by the helium environment, perturbations of the electronically excited states are obs...

  7. Synthesis of steroidal dimers: Selective amine catalysed steroidal dimerization

    Indian Academy of Sciences (India)

    Shamsuzzaman; Mohd Gulfam Aalam; Tabassum Siddiqui

    2011-07-01

    Some new dimeric steroids namely cholest-5-en-3-spiro-[6',5'-oxa]-5'-cholest-3'-one (2), cholest-5-en-7-spiro-[4',5'-oxa]-5'-cholest-7'-one (4a) and 3-substitutedcholest-5-en-7-spiro-[4',5'-oxa]-3'-substituted-5'-cholestan-7'-ones (4b, c) are synthesized starting from cholest-5-en-3-one (1), cholest-5-en-7-one (3a) and 3-substituted-cholest-5-en-7-ones (3b, c) respectively by using DMAP and xylene. All the synthesized compounds were characterized by using IR, MS and 1H, 13C NMR spectral and elemental analysis.

  8. 2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

    Science.gov (United States)

    Somasundaram, S; Simpson, R; Rafi, S; Shergill, JK; Bjarnason, I; Wrigglesworth, J

    2002-01-01

    Background It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. Results Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g ~ 2.01) at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g ~2.07) suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO•). In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. Conclusion The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO• appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity. PMID:11960558

  9. 2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

    Directory of Open Access Journals (Sweden)

    Bjarnason I

    2002-04-01

    Full Text Available Abstract Background It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. Results Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g ~ 2.01 at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g ~2.07 suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO•. In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. Conclusion The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO• appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity.

  10. Infrared study of some 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. Correlation with MO-calculations

    Directory of Open Access Journals (Sweden)

    IVAN O. JURANIC

    2000-06-01

    Full Text Available The IR spectra of a series of 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids (substituent = OH, SH, CH3, CH3S and NH2 were studied from the aspect of the influence of the subsitutent on the polarizability of some bonds, keto-enol tautomerism and hydrogen bond formation. The spectra were taken using solids due to the low solubility of the acids. Theoretical calculations were done using the MNDO-AM1 semiempirical molecular-orbital method. The stabilities of various tautomers were calculated simulating the dielectric continuum using the COSMO facility of the MOPAC program package. Theoretical calculations were made for all the possible tautomers of the 2-substituted-6-hydroxy-4-pyrimidine carboxylic acids. For the most stable isomers, the vibrational spectra were calculated. For the majority of the compounds the most stable isomer was identified having the structure 2-Y-6-oxo-4-carboxy-3H-pyrimidine. Besides this structure, for the 2-amino-, and 2-methyl- derivatives the zwitterionic forms have very similar stability. The 2-hydroxy compound is most stable as the 2,6-dioxo-1H, 3H isomer. The calculated vibrations for the compounds with a single stable structure correlate very well with the experimental frequencies. For the 2-methyl- and 2-amino- compounds the correlation is considerably less satisfactory. The most probable reason for this deviation is the existence of two or more tautomets in equilibrium. The correlation of the measured frequencies and the pKa values of the acids, indicate that the same tautomers exist in the solid state and in the solution.

  11. Thermodynamics of oligomer formation: implications for secondary organic aerosol formation and reactivity.

    Science.gov (United States)

    DePalma, Joseph W; Horan, Andrew J; Hall, Wiley A; Johnston, Murray V

    2013-05-14

    Dimers and higher order oligomers, whether in the gas or particle phase, can affect important atmospheric processes such as new particle formation, and gas-particle partitioning. In this study, the thermodynamics of dimer formation from various oxidation products of α-pinene ozonolysis are investigated using a combination of Monte Carlo configuration sampling, semi-empirical and density functional theory (DFT) quantum mechanics, and continuum solvent modeling. Favorable dimer formation pathways are found to exist in both gas and condensed phases. The free energies of dimer formation are used to calculate equilibrium constants and expected dimer concentrations under a variety of conditions. In the gas phase, favorable pathways studied include formation of non-covalent dimers of terpenylic acid and/or cis-pinic acid and a covalently-bound peroxyhemiacetal. Under atmospherically relevant conditions, only terpenylic acid forms a dimer in sufficient quantities to contribute to new particle formation. Under conditions typically used in laboratory experiments, several dimer formation pathways may contribute to particle formation. In the condensed phase, non-covalent dimers of terpenylic acid and/or cis-pinic acid and covalently-bound dimers representing a peroxyhemiacetal and a hydrated aldol are favorably formed. Dimer formation is both solution and temperature dependent. A water-like solution appears to promote dimer formation over methanol- or acetonitrile-like solutions. Heating from 298 K to 373 K causes extensive decomposition back to monomers. Dimers that are not favorably formed in either the gas or condensed phase include hemi-acetal, ester, anhydride, and the di(α-hydroxy) ether.

  12. Structure and Stability of a Dimeric G-Quadruplex Formed by Cyclic Oligonucleotides

    Directory of Open Access Journals (Sweden)

    Joan Casals

    2010-01-01

    containing two copies of the human telomeric repeat. In the presence of sodium, NMR data are consistent with a dimeric structure of the molecule in which two cycles self-associate forming a quadruplex with three guanine tetrads connected by edgewise loops. The two macrocycles are arranged in a parallel way, and the dimeric structure exhibits a high melting temperature. These results indicate that cyclization of the phosphodiester chain does not prevent quadruplex formation, although it affects the global topology of the quadruplex.

  13. Dimer models and Calabi-Yau algebras

    CERN Document Server

    Broomhead, Nathan

    2008-01-01

    In this thesis we study dimer models, as introduced in string theory, which give a way of writing down a class of non-commutative `superpotential' algebras. Some examples are 3-dimensional Calabi-Yau algebras, as defined by Ginzburg, and some are not. We consider two types of `consistency' condition on dimer models, and show that a `geometrically consistent' model is `algebraically consistent'. Finally we prove that the algebras obtained from algebraically consistent dimer models are 3-dimensional Calabi-Yau algebras.

  14. On Dimer Models and Closed String Theories

    OpenAIRE

    Sarkar, Tapobrata

    2007-01-01

    We study some aspects of the recently discovered connection between dimer models and D-brane gauge theories. We argue that dimer models are also naturally related to closed string theories on non compact orbifolds of $\\BC^2$ and $\\BC^3$, via their twisted sector R charges, and show that perfect matchings in dimer models correspond to twisted sector states in the closed string theory. We also use this formalism to study the combinatorics of some unstable orbifolds of $\\BC^2$.

  15. Inhibition of arenavirus by A3, a pyrimidine biosynthesis inhibitor.

    Science.gov (United States)

    Ortiz-Riaño, Emilio; Ngo, Nhi; Devito, Stefanie; Eggink, Dirk; Munger, Joshua; Shaw, Megan L; de la Torre, Juan Carlos; Martínez-Sobrido, Luis

    2014-01-01

    Arenaviruses merit significant interest as important human pathogens, since several of them cause severe hemorrhagic fever disease that is associated with high morbidity and significant mortality. Currently, there are no FDA-licensed arenavirus vaccines available, and current antiarenaviral therapy is limited to an off-labeled use of the nucleoside analog ribavirin, which has limited prophylactic efficacy. The pyrimidine biosynthesis inhibitor A3, which was identified in a high-throughput screen for compounds that blocked influenza virus replication, exhibits a broad-spectrum antiviral activity against negative- and positive-sense RNA viruses, retroviruses, and DNA viruses. In this study, we evaluated the antiviral activity of A3 against representative Old World (lymphocytic choriomeningitis virus) and New World (Junin virus) arenaviruses in rodent, monkey, and human cell lines. We show that A3 is significantly more efficient than ribavirin in controlling arenavirus multiplication and that the A3 inhibitory effect is in part due to its ability to interfere with viral RNA replication and transcription. We document an additive antiarenavirus effect of A3 and ribavirin, supporting the potential combination therapy of ribavirin and pyrimidine biosynthesis inhibitors for the treatment of arenavirus infections.

  16. Synthesis and characterization of novel Schiff bases containing pyrimidine unit

    Directory of Open Access Journals (Sweden)

    Jumbad H. Tomma

    2014-01-01

    Full Text Available The work involves synthesis of novel Schiff base derivatives containing a pyrimidine unit starting with chalcones. 4-Aminoacetophenone was reacted with 4-nitrobenzaldehyde or 4-chlorobenzaldehyde in basic medium giving chalcones, [I]a and [I]b, respectively, by Claisen-Schemidt reaction. The chalcones [I]a and [I]b were reacted with urea in HCl medium giving oxopyrimidines, [II]a and [II]b. They were also reacted with thiourea in basic medium to give thioxopyrimidines, [III]a and [III]b. The novel mono and bis Schiff bases, [VIII]na, [VIII]nb, [IX]na, [IX]nb, [X]na, [X]nb, [XI]na, and [XI]nb were synthesized by the reaction of pyrimidine derivatives; oxopyrimdines, [II]a and [II]b and thioxopyrimidines, [III]a and [III]b with 4-(4′-n-alkoxybenzoloxybenzaldehyde [VI] and polymethylene-α,ω-bis-4-oxybenzaldehydes [VII]m, respectively, in dry benzene using drops of glacial acetic acid as a catalyst. The synthesized compounds were characterized by melting points, elemental analysis, FTIR, and 1H NMR spectroscopy.

  17. Enhanced Chiral Recognition by Cyclodextrin Dimers

    Directory of Open Access Journals (Sweden)

    Bart Jan Ravoo

    2011-07-01

    Full Text Available In this article we investigate the effect of multivalency in chiral recognition. To this end, we measured the host-guest interaction of a β-cyclodextrin dimer with divalent chiral guests. We report the synthesis of carbohydrate-based water soluble chiral guests functionalized with two borneol, menthol, or isopinocampheol units in either (+ or (– configuration. We determined the interaction of these divalent guests with a β-cyclodextrin dimer using isothermal titration calorimetry. It was found that—in spite of a highly unfavorable conformation—the cyclodextrin dimer binds to guest dimers with an increased enantioselectivity, which clearly reflects the effect of multivalency.

  18. Sputtering of dimers off a silicon surface

    Energy Technology Data Exchange (ETDEWEB)

    Nietiadi, Maureen L. [Physics Department, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Research Center OPTIMAS, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Rosandi, Yudi [Physics Department, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Research Center OPTIMAS, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Department of Physics, Universitas Padjadjaran, Jatinangor, Sumedang 45363 (Indonesia); Kopnarski, Michael [Physics Department, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Research Center OPTIMAS, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Institut fuer Oberflaechen- und Schichtanalytik IFOS GmbH, Trippstadter Strasse 120, D-67663 Kaiserslautern (Germany); Urbassek, Herbert M., E-mail: urbassek@rhrk.uni-kl.de [Physics Department, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany); Research Center OPTIMAS, University Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany)

    2012-10-15

    We present experimental and molecular-dynamics simulation results of the sputtering of a Si surface by 2 keV Ar ions. Results on both the monomer and dimer distributions are presented. In simulation, these distributions follow a generalized Thompson law with power exponent n=2 and n=3, respectively. The experimental data, obtained via plasma post-ionization in an SNMS (secondary neutral mass spectrometry) apparatus, show good agreement with respect to the dimer fraction, and the relative energy distributions of dimers and monomers. The consequences for the dimer sputtering mechanism are discussed.

  19. Crystal structures of two 6-(2-hydroxybenzoyl-5H-thiazolo[3,2-a]pyrimidin-5-ones

    Directory of Open Access Journals (Sweden)

    Ligia R. Gomes

    2015-07-01

    Full Text Available The title compounds, 6-(2-hydroxybenzyl-5H-thiazolo[3,2-a]pyrimidin-5-one, C13H8N2O3S, (1, and 6-(2-hydroxybenzyl-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, C14H10N2O3S, (2, were synthesized when a chromone-3-carboxylic acid, activated with (benzotriazol-1-yloxytripyrrolidinylphosphonium hexafluoridophosphate (PyBOP, was reacted with a primary heteromamine. Instead of the expected amidation, the unusual title thiazolopyrimidine-5-one derivatives were obtained serendipitously and a mechanism of formation is proposed. Both compounds present an intramolecular O—H...O hydrogen bond, which generates an S(6 ring. The dihedral angles between the heterocyclic moiety and the 2-hydroxybenzoyl ring are 55.22 (5 and 46.83 (6° for (1 and (2, respectively. In the crystals, the molecules are linked by weak C—H...O hydrogen bonds and π–π stacking interactions.

  20. Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

    Directory of Open Access Journals (Sweden)

    Jackie Penn

    2015-02-01

    Full Text Available The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE and Bruch’s membrane (BM. However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.

  1. Catabolism of pyrimidines in yeast: a tool to understand degradation of anticancer drugs

    DEFF Research Database (Denmark)

    Andersen, G; Merico, A; Björnberg, O;

    2006-01-01

    The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides....../antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway...

  2. Stopping power for electrons in pyrimidine in the energy range 20-3000 eV.

    Science.gov (United States)

    Colmenares, R; Sanz, A G; Fuss, M C; Blanco, F; García, G

    2014-01-01

    In this work, we present new experimental electron energy loss distribution functions for pyrimidine (C4H4N2) measured for the incident energy range 30-2000 eV. Theoretical total and elastic cross sections for electron scattering from pyrimidine were calculated using the screening-corrected additivity rule (IAM-SCAR) method. Based on the mean energy loss observed in the experiment and the theoretical integral inelastic cross section, the stopping power for electrons in pyrimidine is calculated in the energy range 20-3000 eV.

  3. Catabolism of pyrimidines in yeast: A tool to understand degradation of anticancer drugs

    DEFF Research Database (Denmark)

    Andersen, Gorm; Merico, A.; Bjornberg, O.

    2006-01-01

    The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides....../antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway...

  4. An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry

    Directory of Open Access Journals (Sweden)

    M. Mamaghani

    2014-01-01

    Full Text Available In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio-pyrimidin-4(3Hone, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97% and short reaction times (10–33 min.

  5. An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry

    OpenAIRE

    2014-01-01

    In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3H)one, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97%) and short reaction times (10–33 min).

  6. Intramolecular hydrophobic interactions are critical mediators of STAT5 dimerization

    Science.gov (United States)

    Fahrenkamp, Dirk; Li, Jinyu; Ernst, Sabrina; Schmitz-van de Leur, Hildegard; Chatain, Nicolas; Küster, Andrea; Koschmieder, Steffen; Lüscher, Bernhard; Rossetti, Giulia; Müller-Newen, Gerhard

    2016-10-01

    STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins. We identified a novel intramolecular interaction mediated through F706, adjacent to the phosphotyrosine motif, and a unique hydrophobic interface on the surface of the SH2 domain. Analysis of corresponding STAT5 mutants revealed that this interaction is dispensable for Epo receptor-mediated phosphorylation of STAT5 but essential for dimer formation and subsequent nuclear accumulation. Moreover, the herein presented model clarifies molecular mechanisms of recently discovered leukemic STAT5 mutants and will help to guide future drug development.

  7. Measurement of oxidative damage at pyrimidine bases in gamma-irradiated DNA.

    Science.gov (United States)

    Douki, T; Delatour, T; Paganon, F; Cadet, J

    1996-01-01

    Oxidized nucleobases represent one of the main classes of damage induced in DNA by ionizing radiation. Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5-(hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxycytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra), in isolated DNA upon exposure to gamma radiation in aerated aqueous solution. For this purpose, both high performance liquid chromatography associated with electrochemical detection (HPLC-EC) and gas chromatography coupled to mass spectrometry (GC-MS) were used. Conditions of hydrolysis of the N-glycosidic bond were carefully checked in order to achieve a quantitative release of the lesions. We showed that 60% formic acid treatment leads to the decomposition of the four lesions studied. On the other hand, hydrolysis based on the use of either 88% formic acid or 70% hydrogen fluoride in pyridine (HF/Pyr) allowed the quantitative release of the modified bases, with the exception of 5-HMUra when the latter reagent was utilized. A dose course study of the radiation-induced formation of 5-HMUra and 5-ForUra in DNA by using the GC-MS assay showed that the latter lesion was produced in a 2.1-fold higher yield than the former one. HF/Pyr and 88% formic acid hydrolysis provided similar results for 5-ForUra, indicating the reliability of both techniques for the measurement of this lesion. For 5-OHUra and 5-OHCyt, the level of modification determined by GC-MS analysis was higher after 88% formic acid treatment than upon HF/Pyr hydrolysis. When DNA was enzymatically digested and analyzed by HPLC-EC for 5-OHdCyd and 5-OHdUrd, the results were very close to those obtained by GC-MS following HF/Pyr treatment. It was concluded that additional amounts of both 5-OHUra and 5-OHCyt are produced during the 88% formic acid treatment from radiation-induced 5,6-saturated pyrimidine precursors. It is likely that cytosine and uracil diols are involved in this reaction. The

  8. Mahler Measure, Eisenstein Series and Dimers

    NARCIS (Netherlands)

    Stienstra, J.

    2007-01-01

    This note reveals a mysterious link between the partition function of certain dimer models on 2-dimensional tori and the L-function of their spectral curves. It also relates the partition function in certain families of dimer models to Eisenstein series. http://www.arxiv.org/abs/math.NT/0502197

  9. Dimeric assembly of enterocyte brush border enzymes

    DEFF Research Database (Denmark)

    Danielsen, E M

    1994-01-01

    temperature (20 degrees C) reduced the rate of, but did not prevent, dimerization. Maltase-glucoamylase (EC 3.2.1.20) only appeared as a dimer when extracted and analyzed under low salt conditions, suggesting a weak association between the two subunits. This finding is consistent with the electronmicroscopic...

  10. Dimerization of the D1 dopamine receptors is related with agonist and inverse agonist-induced receptor internalization

    Institute of Scientific and Technical Information of China (English)

    Yi-minTAO; Xue-junXU; Min-huaHONG; JieCHEN; Zhi-qiangCHI; Jing-genLIU

    2004-01-01

    AIM: To examine the relationship between D1 dopamine receptor dimer formation and ligand-induced receptor internalization. METHODS: FLAG-tagged D 1 dopamine receptor was transiently expressed in Sf9 cells. The cells were treated with SKF38393 or (+)butaclamol 1 μmol/L for different periods timeor at different doses for 30 min respectively. Western blot assaywas performed to assess dimer formation and flow evtomv.tv.r

  11. Statistical transmutation in doped quantum dimer models.

    Science.gov (United States)

    Lamas, C A; Ralko, A; Cabra, D C; Poilblanc, D; Pujol, P

    2012-07-06

    We prove a "statistical transmutation" symmetry of doped quantum dimer models on the square, triangular, and kagome lattices: the energy spectrum is invariant under a simultaneous change of statistics (i.e., bosonic into fermionic or vice versa) of the holes and of the signs of all the dimer resonance loops. This exact transformation enables us to define the duality equivalence between doped quantum dimer Hamiltonians and provides the analytic framework to analyze dynamical statistical transmutations. We investigate numerically the doping of the triangular quantum dimer model with special focus on the topological Z(2) dimer liquid. Doping leads to four (instead of two for the square lattice) inequivalent families of Hamiltonians. Competition between phase separation, superfluidity, supersolidity, and fermionic phases is investigated in the four families.

  12. Dimerization of tetherin is not essential for its antiviral activity against Lassa and Marburg viruses.

    Directory of Open Access Journals (Sweden)

    Toshie Sakuma

    Full Text Available Tetherin (also known as BST2, CD317 or HM1.24 has recently been reported to inhibit a wide range of viruses. However, the antiviral mechanism of action of tetherin has not been determined. Both ends of the tetherin molecule are associated with the plasma membrane and it forms a homodimer. Therefore, a model in which progeny virions are retained on the cell surface by dimer formation between tetherin molecules on the viral envelope and plasma membrane has been proposed as the antiviral mechanism of action of this molecule. To investigate this possibility, we examined the correlation between dimerization and antiviral activity of tetherin in Lassa and Marburg virus-like particle production systems using tetherin mutants deficient in dimer formation. However, the tetherin mutant with complete loss of dimerization activity still showed apparent antiviral activity, indicating that dimerization of tetherin is not essential for its antiviral activity. This suggests that tetherin retains progeny virions on the cell surface by a mechanism other than dimerization.

  13. Biosynthesis of intestinal microvillar proteins. Dimerization of aminopeptidase N and lactase-phlorizin hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    Danielsen, E.M. (Univ. of Cophenhagen (Denmark))

    1990-01-09

    The pig intestinal brush border enzymes aminopeptidase and lactase-phlorizin hydrolase are present in the microvilla membrane as homodimers. Dimethyl adipimidate was used to cross-link the two ({sup 35}S)methionine-labeled brush border enzymes from cultured mucosal explants. For aminopeptidase N, dimerization did not begin until 5-10 min after synthesis, and maximal dimerization by cross-linking of the transient form of the enzyme required 1 h, whereas the mature form of aminopeptidase N cross-linked with unchanged efficiency from 45 min to 3 h of labeling. Formation of dimers of this enzyme therefore occurs prior to the Golgi-associated processing, and the slow rate of dimerization may be the rate-limiting step in the transport from the endoplasmic reticulum to the Golgi complex. For lactase-phlorizin hydrolase, the posttranslational processing includes a proteolytic cleavage of its high molecular weight precursor. Since only the mature form and not the precursor of this enzyme could be cross-linked, formation of tightly associated dimers only takes place after transport out of the endoplasmic reticulum. Dimerization of the two brush border enzymes therefore seems to occur in different organelles of the enterocyte.

  14. Biosynthesis of intestinal microvillar proteins. Dimerization of aminopeptidase N and lactase-phlorizin hydrolase

    DEFF Research Database (Denmark)

    Danielsen, E M

    1990-01-01

    The pig intestinal brush border enzymes aminopeptidase N (EC 3.4.11.2) and lactase-phlorizin hydrolase (EC 3.2.1.23-62) are present in the microvillar membrane as homodimers. Dimethyl adipimidate was used to cross-link the two [35S]methionine-labeled brush border enzymes from cultured mucosal...... explants. For aminopeptidase N, dimerization did not begin until 5-10 min after synthesis, and maximal dimerization by cross-linking of the transient form of the enzyme required 1 h, whereas the mature form of aminopeptidase N cross-linked with unchanged efficiency from 45 min to 3 h of labeling. Formation...... of dimers of this enzyme therefore occurs prior to the Golgi-associated processing, and the slow rate of dimerization may be the rate-limiting step in the transport from the endoplasmic reticulum to the Golgi complex. For lactase-phlorizin hydrolase, the posttranslational processing includes a proteolytic...

  15. Synthesis and comparing the antibacterial activities of pyrimidine derivatives

    Indian Academy of Sciences (India)

    B ANDREWS; K KOMATHI; S MOHAN

    2017-03-01

    A series of 10 derivatives of 5-(5-amino-1,3,4-thiadiazole-2-yl)-3,4-dihydro-6-methyl-4-phenylpyrimidin-2(1H)-one and 10 derivatives of 3,4-dihydro-5-(5-mercapto-4H-1,2,4-triazol-3-yl)-6-methyl-4-phenyl pyrimidin-2(1H)-one have been synthesized. Among the synthesized derivatives, triazole substitutedcompounds have shown higher antibacterial inhibition when compared to the thiadiazole derivatives. All the structures of the newly synthesized compounds have been characterized by IR, 1H and 13C NMR, GC-MS and CHN analysis. Most of the compounds have shown promising antibacterial activity when compared with the standard drug ciprofloxacin.

  16. New insights on pyrimidine signalling within the arterial vasculature

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Spray, Stine; Syberg, Susanne;

    2016-01-01

    and relaxation in the coronary circulation and to establish whether P2Y receptors have different functions along the mouse coronary vascular tree. We tested stable pyrimidine analogues on isolated coronary arteries from P2Y2 and P2Y6 receptor KO mice in a myograph setup. In larger diameter segments of the left...... descending coronary artery (LAD) (lumen diameter~150μm) P2Y6 is the predominant contractile receptor for both UTP (uridine triphosphate) and UDP (uridine diphosphate) induced contraction. In contrast, P2Y2 receptors mediate endothelial-dependent relaxation. However, in smaller diameter LAD segments (lumen...... diameter~50μm), the situation is opposite, with P2Y2 being the contractile receptor and P2Y6 functioning as a relaxant receptor along with P2Y2. Immunohistochemistry was used to confirm smooth muscle and endothelial localization of the receptors. In vivo measurements of blood pressure in WT mice revealed...

  17. 1,4-Bis(pyrimidin-2-ylsulfanylbutane

    Directory of Open Access Journals (Sweden)

    Muhammad Akbar

    2010-11-01

    Full Text Available The –SCH2CH2CH2CH2S– portion of the title compound, C12H14N2S2, adopts an extended zigzag conformation. The angles at the tetrahedral carbon atoms are marginally increased [113.63 (12° and 111.38 (17° for S—C—C and C—C—C respectively] from the idealized tetrahedral angle. The molecule lies on an inversion center located at the mid-point of the butyl chain. In the crystal, there is a π–π stacking interaction between inversion-related pyrimidine rings with mean interplanar spacing of 3.494 (2 Å.

  18. Dimerization of the glucan phosphatase laforin requires the participation of cysteine 329.

    Directory of Open Access Journals (Sweden)

    Pablo Sánchez-Martín

    Full Text Available Laforin, encoded by a gene that is mutated in Lafora Disease (LD, OMIM 254780, is a modular protein composed of a carbohydrate-binding module and a dual-specificity phosphatase domain. Laforin is the founding member of the glucan-phosphatase family and regulates the levels of phosphate present in glycogen. Multiple reports have described the capability of laforin to form dimers, although the function of these dimers and their relationship with LD remains unclear. Recent evidence suggests that laforin dimerization depends on redox conditions, suggesting that disulfide bonds are involved in laforin dimerization. Using site-directed mutagenesis we constructed laforin mutants in which individual cysteine residues were replaced by serine and then tested the ability of each protein to dimerize using recombinant protein as well as a mammalian cell culture assay. Laforin-Cys329Ser was the only Cys/Ser mutant unable to form dimers in both assays. We also generated a laforin truncation lacking the last three amino acids, laforin-Cys329X, and this truncation also failed to dimerize. Interestingly, laforin-Cys329Ser and laforin-Cys329X were able to bind glucans, and maintained wild type phosphatase activity against both exogenous and biologically relevant substrates. Furthermore, laforin-Cys329Ser was fully capable of participating in the ubiquitination process driven by a laforin-malin complex. These results suggest that dimerization is not required for laforin phosphatase activity, glucan binding, or for the formation of a functional laforin-malin complex. Cumulatively, these results suggest that cysteine 329 is specifically involved in the dimerization process of laforin. Therefore, the C329S mutant constitutes a valuable tool to analyze the physiological implications of laforin's oligomerization.

  19. CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity.

    Science.gov (United States)

    Liu, Jiping; Deng, Ya-Hui; Yang, Ling; Chen, Yijuan; Lawali, Manzo; Sun, Li-Ping; Liu, Yu

    2015-09-01

    Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5-methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU-12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50 value at 9.30 ± 1.24 μM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex-vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti-angiogenic activity in vitro. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  20. Mutational Analysis and Allosteric Effects in the HIV-1 Capsid Protein Carboxyl-Terminal Dimerization Domain

    Science.gov (United States)

    2009-01-01

    The carboxyl-terminal domain (CTD, residues 146−231) of the HIV-1 capsid (CA) protein plays an important role in the CA−CA dimerization and viral assembly of the human immunodeficiency virus type 1. Disrupting the native conformation of the CA is essential for blocking viral capsid formation and viral replication. Thus, it is important to identify the exact nature of the structural changes and driving forces of the CTD dimerization that take place in mutant forms. Here, we compare the structural stability, conformational dynamics, and association force of the CTD dimers for both wild-type and mutated sequences using all-atom explicit-solvent molecular dynamics (MD). The simulations show that Q155N and E159D at the major homology region (MHR) and W184A and M185A at the helix 2 region are energetically less favorable than the wild-type, imposing profound negative effects on intermolecular CA−CA dimerization. Detailed structural analysis shows that three mutants (Q155N, E159D, and W184A) display much more flexible local structures and weaker CA−CA association than the wild-type, primarily due to the loss of interactions (hydrogen bonds, side chain hydrophobic contacts, and π-stacking) with their neighboring residues. Most interestingly, the MHR that is far from the interacting dimeric interface is more sensitive to the mutations than the helix 2 region that is located at the CA−CA dimeric interface, indicating that structural changes in the distinct motif of the CA could similarly allosterically prevent the CA capsid formation. In addition, the structural and free energy comparison of the five residues shorter CA (151−231) dimer with the CA (146−231) dimer further indicates that hydrophobic interactions, side chain packing, and hydrogen bonds are the major, dominant driving forces in stabilizing the CA interface. PMID:19199580

  1. Bis(pyrimidine-2-carboxylato-κ2N,Ocopper(II

    Directory of Open Access Journals (Sweden)

    Bing-Yu Zhang

    2008-01-01

    Full Text Available The title compound, [Cu(C5H3N2O22], was prepared in a water–ethanol solution containing 2-cyanopyrimidine, malonic acid and copper(II nitrate trihydrate. The CuII ion, located on an inversion center, is chelated by two pyrimidine-2-carboxylate anions in a CuO2N2 square-planar geometry. The uncoordinated carboxylate O atom and pyrimidine N atoms are linked to adjacent pyrimidine rings via weak C—H...O and C—H...N hydrogen bonding. π–π Stacking is observed between nearly parallel pyrimidine rings, the centroid-to-centroid separation being 3.8605 (13 Å.

  2. divalent metal complexes of 4-amino-n-pyrimidin-2-ylbenzene ...

    African Journals Online (AJOL)

    Preferred Customer

    use of metal complexes as chemotherapeutic drugs has become a vibrant and growing area of ..... through the pyrimidine nitrogen atom [17]. ... binding can take place by the acceptance of a one pair of electron from the donor nitrogen atom.

  3. Absorption and Intermediary Metabolism of Purines and Pyrimidines in Lactating Dairy Cows

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Stentoft; Røjen, Betina Amdisen; Jensen, Søren Krogh

    2015-01-01

    About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic...... metabolism were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was sampled simultaneously from four veins with eight hourly samples from four multi-catheterised Holstein cows. Quantification of twenty purines and pyrimidines was performed with HPLC–MS/MS, and net fluxes were estimated...... across the PDV, hepatic tissue and total splanchnic tissue (TSP). Concentration differences between veins of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation products (DP) were different from zero (P≤ 0·05), resulting in the net PDV releases of purine NS (0·33–1·3 mmol...

  4. Synthesis of 2-Arylimidazo[1,2-a]pyrimidines in Ionic Liquids

    Institute of Scientific and Technical Information of China (English)

    Dan Qian XU; Bao You LIU; Zhen Yuan XU

    2003-01-01

    Room temperature ionic liquids were used as a "green" recyclable alternative toconventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a]pyrimidines through Tschotschibabin reaction of α-bromoacetophenones with 2-aminopyfinidinein good yields.

  5. Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors.

    Science.gov (United States)

    Bukhari, S N A; Butt, A M; Amjad, M W B; Ahmad, W; Shah, V H; Trivedi, A R

    2013-11-01

    Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.

  6. Smectic Phase Formed by DNA Dimers

    Science.gov (United States)

    Salamonczyk, Miroslaw; Gleeson, James; Jakli, Antal; Sprunt, Samuel; Dhont, Jan; Stiakakis, Emmanuel

    The rapidly expanding bio market is driving the development and characterization of new multifunctional materials. In particular, nucleic acids are under intense study for gene therapy, drug delivery and other bio-safe applications [1,2,3]. DNA is well-known to form a cholesteric nematic liquid crystal in its native form; however, much recent research has focused on self-assembly and mesomorphic behavior in concentrated solutions of short DNA helices [4]. Our work focuses on DNA dimers, consisting of 48 base-pair double-stranded helices connected by a 5 to 20 base flexible single strand, and suspended in a natural buffer. Depending on temperature, concentration and length of the flexible spacer, polarizing optical microscopy and small angle x-ray scattering reveal cholesteric nematic and, remarkably, smectic liquid crystalline phases. A model for smectic phase formation in this system will be presented. 1] J.-L. Lim et al., Int. J. of. Pharm. 490 (2015) 2652] D.-H. Kim et al., Nature Biotech. 23 (2005) 2223] K. Liu et al., Chem. Eur. J. 21 (2015) 48984] M. Nakata et al., Science 318 (2007) 1276 NSF DMR 1307674.

  7. The 3-ureidopropionase of Caenorhabditis elegans, an enzyme involved in pyrimidine degradation.

    Science.gov (United States)

    Janowitz, Tim; Ajonina, Irene; Perbandt, Markus; Woltersdorf, Christian; Hertel, Patrick; Liebau, Eva; Gigengack, Ulrike

    2010-10-01

    Pyrimidines are important metabolites in all cells. Levels of cellular pyrimidines are controlled by multiple mechanisms, with one of these comprising the reductive degradation pathway. In the model invertebrate Caenorhabditis elegans, two of the three enzymes of reductive pyrimidine degradation have previously been characterized. The enzyme catalysing the final step of pyrimidine breakdown, 3-ureidopropionase (β-alanine synthase), had only been identified based on homology. We therefore cloned and functionally expressed the 3-ureidopropionase of C. elegans as hexahistidine fusion protein. The purified recombinant enzyme readily converted the two pyrimidine degradation products: 3-ureidopropionate and 2-methyl-3-ureidopropionate. The enzyme showed a broad pH optimum between pH 7.0 and 8.0. Activity was highest at approximately 40 °C, although the half-life of activity was only 65 s at that temperature. The enzyme showed clear Michaelis-Menten kinetics, with a K(m) of 147 ± 26 μM and a V(max) of 1.1 ± 0.1 U·mg protein(-1). The quaternary structure of the recombinant enzyme was shown to correspond to a dodecamer by 'blue native' gel electrophoresis and gel filtration. The organ specific and subcellular localization of the enzyme was determined using a translational fusion to green fluorescent protein and high expression was observed in striated muscle cells. With the characterization of the 3-ureidopropionase, the reductive pyrimidine degradation pathway in C. elegans has been functionally characterized.

  8. Structural and spectral characteristics of the cross-linked dimer derived from electrooxidation of cyclic 1,N2-propanoguanosine.

    Science.gov (United States)

    Murakami, Hiroya; Esaka, Yukihiro; Uno, Bunji

    2011-01-01

    The acetaldehyde-derived cyclic propano adduct of 2'-deoxyguanosine was easily oxidized electrochemically into the cross-linked dimer as an oxidative product. The structural and spectroscopic characteristics of the dimer were investigated by MS, (1)H and (13)C-NMR, UV, and DFT calculations. The dimer formation was inferred from a molecular ionic peak of m/z 705 ([(2M-2H)+H](+), M being the molecular weight of the monomer) on the ESI-MS spectra and the chemical formula as C(28)H(36)N(10)O(12) provided by the high-resolution ESI-MS results. The C2-N5 linkage between the two monomers in the dimer was deduced from the (1)H- and (13)C-NMR spectral results. In addition, the correlations in the 2-dimensional NMR spectra (DQF-COSY and HMBC) were consistently explained by the structure of the C2-N5 cross-linked dimer. UV spectral measurements also support the C2-N5 linking in the dimer formation. The formation of the cross-link dimer as an oxidative lesion of the acetaldehyde-derived cyclic propano adduct of guanosine is expected to interfere with DNA replication and to contribute to acetaldehyde-mediated genotoxicity.

  9. Investigating the role of vibrational excitation in simulating charged-particle tracks in liquid pyrimidine

    Science.gov (United States)

    Brunger, Michael J.; Ratnavelu, Kuru; Buckman, Stephen J.; Jones, Darryl B.; Muñoz, Antonio; Blanco, Francisco; García, Gustavo

    2016-03-01

    We report on our results of a study into the sensitivity of charged-particle (electron) track simulations in liquid pyrimidine, to the vibrational cross sections and vibrational energy loss distribution function employed in those simulations. We achieve this by repeating the earlier investigation of Fuss et al. [J. Appl. Phys. 117, 214701 (2015)], but now incorporating more accurate data for the vibrational integral cross sections and the energy loss distribution function that have recently become available. We find that while changes in absorbed dose or particle range are quite minor, due to the energy transferred via vibrational excitations being low in comparison to that for other processes such as ionisation, at the very end of the tracks, where non-ionizing interactions dominate, the significantly large numbers of vibrational excitation processes increases the electrons' ability to induce other effects (e.g. sample heating, bond breaking and radical formation) that might cause damage. Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  10. Dimerization of HCN in the gas phase: A theoretical mechanistic study

    Science.gov (United States)

    Yim, Min Kyoung; Choe, Joong Chul

    2012-06-01

    Potential energy surfaces for the formation of covalently bound HCN dimers from two molecules of HCN or HNC were determined from CBS-QB3/APNO calculations. Several novel pathways, with and without the aid of protons, were found for the formation of iminoacetonitrile (HNdbnd CHCN), an intermediate in adenine synthesis from HCN by oligomerization. Covalent C-C or C-N bonds between the two monomers were formed after rearrangement of bimolecular complex intermediates. Energetic and kinetic analyses suggest that the proton-catalyzed dimerizations substantially lower reaction barriers but cannot occur efficiently under interstellar conditions.

  11. Nonlinearity and trapping in excitation transfer Dimers and Trimers.

    CERN Document Server

    Barvik, I; Schanz, H; Barvik, Ivan; Esser, Bernd; Schanz, Holger

    1995-01-01

    We study the interplay between nonlinearity in exciton transport and trapping due to a sink site for the dimer and the trimer with chain configuration by a numerical integration of the discrete nonlinear Schroedinger equation. Our results for the dimer show, that the formation of a self trapped state due to the nonlinear coupling increases the life time of the exciton substantially. Self trapping can be enhanced by the sink for short times, but for long times it disappears. In the trimer consisting of a subdimer extended by a sink site exists a transition between states localized on the two sites of the subdimer before for larger nonlinear coupling self trapping on one site of the subdimer is observed. For large trapping rates the fear of death effect leads to an increasing life time of the excitation on both, the dimer and the trimer. The sink site is then effectively decoupled. We explain this effect using an asymptotic theory for strong trapping and demonstrate it by direct numerical computation.

  12. Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N-substituted amino and N-sulfonamide derivatives of pyrimidines.

    Science.gov (United States)

    Elgemeie, Galal H; Salah, Ali M; Abbas, Nermeen S; Hussein, Hoda A; Mohamed, Reham A

    2017-03-04

    A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.

  13. Quantum dimer model for the pseudogap metal

    Science.gov (United States)

    Punk, Matthias; Allais, Andrea; Sachdev, Subir

    2015-01-01

    We propose a quantum dimer model for the metallic state of the hole-doped cuprates at low hole density, p. The Hilbert space is spanned by spinless, neutral, bosonic dimers and spin S=1/2, charge +e fermionic dimers. The model realizes a “fractionalized Fermi liquid” with no symmetry breaking and small hole pocket Fermi surfaces enclosing a total area determined by p. Exact diagonalization, on lattices of sizes up to 8×8, shows anisotropic quasiparticle residue around the pocket Fermi surfaces. We discuss the relationship to experiments. PMID:26195771

  14. Quantum dimer model for the pseudogap metal.

    Science.gov (United States)

    Punk, Matthias; Allais, Andrea; Sachdev, Subir

    2015-08-04

    We propose a quantum dimer model for the metallic state of the hole-doped cuprates at low hole density, p. The Hilbert space is spanned by spinless, neutral, bosonic dimers and spin S = 1/2, charge +e fermionic dimers. The model realizes a "fractionalized Fermi liquid" with no symmetry breaking and small hole pocket Fermi surfaces enclosing a total area determined by p. Exact diagonalization, on lattices of sizes up to 8 × 8, shows anisotropic quasiparticle residue around the pocket Fermi surfaces. We discuss the relationship to experiments.

  15. Glutamine-dependent carbamoyl-phosphate synthetase and other enzyme activities related to the pyrimidine pathway in spleen of Squalus acanthias (spiny dogfish).

    Science.gov (United States)

    Anderson, P M

    1989-07-15

    The first two steps of urea synthesis in liver of marine elasmobranchs involve formation of glutamine from ammonia and of carbamoyl phosphate from glutamine, catalysed by glutamine synthetase and carbamoyl-phosphate synthetase, respectively [Anderson & Casey (1984) J. Biol. Chem. 259, 456-462]; both of these enzymes are localized exclusively in the mitochondrial matrix. The objective of this study was to establish the enzymology of carbamoyl phosphate formation and utilization for pyrimidine nucleotide biosynthesis in Squalus acanthias (spiny dogfish), a representative elasmobranch. Aspartate carbamoyltransferase could not be detected in liver of dogfish. Spleen extracts, however, had glutamine-dependent carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, dihydro-orotase, and glutamine synthetase activities, all localized in the cytosol; dihydro-orotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine-5'-decarboxylase activities were also present. Except for glutamine synthetase, the levels of all activities were very low. The carbamoyl-phosphate synthetase activity is inhibited by UTP and is activated by 5-phosphoribosyl 1-pyrophosphate. The first three enzyme activities of the pyrimidine pathway were eluted in distinctly different positions during gel filtration chromatography under a number of different conditions; although complete proteolysis of inter-domain regions of a multifunctional complex during extraction cannot be excluded, the evidence suggests that in dogfish, in contrast to mammalian species, these three enzymes of the pyrimidine pathway exist as individual polypeptide chains. These results: (1) establish that dogfish express two different glutamine-dependent carbamoyl-phosphate synthetase activities, (2) confirm the report [Smith, Ritter & Campbell (1987) J. Biol. Chem. 262, 198-202] that dogfish express two different glutamine synthetases, and (3) provide indirect evidence that glutamine may not be available in liver for

  16. Effect of the cyclobutane cytidine dimer on the properties of Escherichia coli DNA photolyase.

    Science.gov (United States)

    Murphy, Anar K; Tammaro, Margaret; Cortazar, Frank; Gindt, Yvonne M; Schelvis, Johannes P M

    2008-11-27

    Cyclobutane pyrimidine dimer (CPD) photolyases are structure specific DNA-repair enzymes that specialize in the repair of CPDs, the major photoproducts that are formed upon irradiation of DNA with ultraviolet light. The purified enzyme binds a flavin adenine dinucleotide (FAD), which is in the neutral radical semiquinone (FADH(*)) form. The CPDs are repaired by a light-driven, electron transfer from the anionic hydroquinone (FADH(-)) singlet excited state to the CPD, which is followed by reductive cleavage of the cyclobutane ring and subsequent monomerization of the pyrimidine bases. CPDs formed between two adjacent thymidine bases (TT) are repaired with greater efficiency than those formed between two adjacent cytidine bases (CC). In this paper, we investigate the changes in Escherichia coli photolyase that are induced upon binding to DNA containing CC lesions using resonance Raman, UV-vis absorption, and transient absorption spectroscopies, spectroelectrochemistry, and computational chemistry. The binding of photolyase to a CC lesion modifies the energy levels of FADH(*), the rate of charge recombination between FADH(-) and Trp(306)(*), and protein-FADH(*) interactions differently than binding to a TT lesion. However, the reduction potential of the FADH(-)/FADH(*) couple is modified in the same way with both substrates. Our calculations show that the permanent electric dipole moment of CC is stronger (12.1 D) and oriented differently than that of TT (8.7 D). The possible role of the electric dipole moment of the CPD in modifying the physicochemical properties of photolyase as well as in affecting CPD repair will be discussed.

  17. Quantitative analysis of cyclic dimer fatty acid content in the dimerization product by proton NMR spectroscopy.

    Science.gov (United States)

    Park, Kyun Joo; Kim, Minyoung; Seok, Seunghwan; Kim, Young-Wun; Kim, Do Hyun

    2015-01-01

    In this work, (1)H NMR is utilized for the quantitative analysis of a specific cyclic dimer fatty acid in a dimer acid mixture using the pseudo-standard material of mesitylene on the basis of its structural similarity. Mesitylene and cyclic dimer acid levels were determined using the signal of the proton on the cyclic ring (δ=6.8) referenced to the signal of maleic acid (δ=6.2). The content of the cyclic dimer fatty acid was successfully determined through the standard curve of mesitylene and the reported equation. Using the linearity of the mesitylene curve, the cyclic dimer fatty acid in the oil mixture was quantified. The results suggest that the proposed method can be used to quantify cyclic compounds in mixtures to optimize the dimerization process.

  18. [Principles of the hydrolysis of bound purine and pyrimidine bases in foods and program-controlled calculation of nucleic acid content].

    Science.gov (United States)

    Herbel, W; Montag, A

    1987-01-01

    In order to determine the amount of combined purine and pyrimidine bases in foods we investigated the chemical fundamentals of their hydrolytic digestion it was demonstrated that the digestion mixture used, containing trifluoracetic- and formic acids, protected the purine bases during hydrolysis from oxidative degradation due to carbon monoxide formation. Further, a time-saving computer-program was developed and presented. This program allows, depending on the purine composition, the calculation of the corresponding nucleic acids, the nucleotides and the purine-nitrogen-content of the food.

  19. Hexafluoroisopropyl alcohol mediated synthesis of 2,3-dihydro-4H-pyrido[1,2-a]pyrimidin-4-ones

    Science.gov (United States)

    Alam, Mohammad A.; Alsharif, Zakeyah; Alkhattabi, Hessa; Jones, Derika; Delancey, Evan; Gottsponer, Adam; Yang, Tianhong

    2016-11-01

    An efficient synthesis of novel 2,3-dihydro-4H-pyrido[1,2-a]pyrimidin-4-ones has been reported. Inexpensive and readily available substrates, environmentally benign reaction condition, and product formation up to quantitative yield are the key features of this methodology. Products are formed by the aza-Michael addition followed by intramolecular acyl substitution in a domino process. The polar nature and strong hydrogen bond donor capability of 1,1,1,3,3,3-hexafluoropropan-2-ol is pivotal in this cascade protocol.

  20. Approach for in vivo protein binding of 5-n-butyl-pyrazolo[1,5-a]pyrimidine bioactivated in chimeric mice with humanized liver by two-dimensional electrophoresis with accelerator mass spectrometry.

    Science.gov (United States)

    Yamazaki, Hiroshi; Kuribayashi, Shunji; Inoue, Tae; Tateno, Chise; Nishikura, Yasufumi; Oofusa, Ken; Harada, Daisuke; Naito, Shinsaku; Horie, Toru; Ohta, Shigeru

    2010-01-01

    Drug development of a potential analgesic agent 5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimidine was withdrawn because of its limited hepatotoxic effects in humans that could not be predicted from regulatory animal or in vitro studies. In vivo formation of glutathione conjugates and covalent binding of a model compound 5-n-butyl-pyrazolo[1,5-a]pyrimidine were investigated in the present study after intravenous administration to chimeric mice with a human or rat liver because of an interesting capability of human cytochrome P450 1A2 in forming a covalently bound metabolite in vitro. Rapid distribution and elimination of radiolabeled 5-n-butyl-pyrazolo[1,5-a]pyrimidine in plasma or liver fractions were seen in chimeric mice after intravenous administration. However, similar covalent binding in liver was detected over 0.17-24 h after intravenous administration. Radio-LC analyses revealed that the chimeric mice with humanized liver preferentially gave the 3-hydroxylated metabolite and its glutathione conjugate in the plasma and liver. On the contrary, chimeric mice with a rat liver had some rat-specific metabolites in vivo. Analyses by electrophoresis with accelerator mass spectrometry of in vivo radiolabeled liver proteins in chimeric mice revealed that bioactivated 5-n-butyl-pyrazolo[1,5-a]pyrimidine bound nonspecifically to a variety of microsomal proteins including human P450 1A2 as well as cytosolic proteins in the livers from chimeric mice with humanized liver. These results suggest that the hepatotoxic model compound 5-n-butyl-pyrazolo[1,5-a]pyrimidine was activated by human liver microsomal P450 1A2 to reactive intermediate(s) in vivo in humanized chimeric mice and could relatively nonspecifically bind to biomolecules such as P450 1A2 and other proteins.

  1. A New Dimeric Phthalide from Angelica sinensis

    Institute of Scientific and Technical Information of China (English)

    Ling YI; Ping LI; Zhi Ming BI

    2006-01-01

    A new dimeric phthalide named Z, Z'-3.3'a, 7.7'a-diligustilide was isolated from the roots of Angelica sinensis. Its structure was determined using spectroscopic methods and X-ray crystallographic diffraction analysis.

  2. Spectroscopic and thermodynamic evidence of dimer and trimer hydrogen bonded complex formation between chloroform and 2-butanone. Excess Molar enthalpy for the chloroform + 2-butanone binary system at 303 K.

    Science.gov (United States)

    Gómez Marigliano, Ana C; Campos, Viviana del Valle; Fernández, Lis; Roldán, M L; Sólimo, Horacio N

    2013-05-02

    FT-Raman and FT-infrared spectra of pure chloroform (A) and 2-butanone (B), as well as of the binary system chloroform + 2-butanone, were recorded to investigate the type and nature of the intermolecular complexes formed when both chemicals are mixed. The optimized structures and vibrational frequencies for 2-butanone, chloroform, and their 1:1 and 1:2 complexes were calculated by means of density functional theory (DFT) techniques using the B3LYP functional combined with the 6-31G(d,p) and 6-311++G(d,p) basis set. The recorded FTIR and Raman spectra confirm the existence of these types of hydrogen-bonded complexes, making it possible, furthermore, to calculate the heteroassociation constants. Heat of mixing at 303 K over the whole mole fraction range at atmospheric pressure was also measured. The excess molar enthalpy was fitted to a Redlich-Kister-type equation, using least-squares to obtain its dependence on concentration. The ideal associated solution model was also used to calculate these equilibrium constants among the chemical species in solution, which compare well with that calculated with the spectral determinations and the enthalpy of hydrogen bond formation. Furthermore, the McGlashan-Rastogi linearization test was also used to provide thermodynamic evidence about the stoichiometry of the formed complexes.

  3. Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro.

    Science.gov (United States)

    Zhang, Jin; Peng, Ju-Fang; Bai, Yu-Bin; Wang, Ping; Wang, Tao; Gao, Jin-Ming; Zhang, Zun-Ting

    2016-11-01

    5,6-Diarylpyrazolo[1,5-a]pyrimidines (3) and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4) were chemoselectively synthesized by the condensation of isoflavone (1) and 3-aminopyrazole (2). 5,6-Diarylpyrazolo[1,5-a]pyrimidines (3) were obtained via microwave irradiation, and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4) were obtained via conventional heating. In addition, the pyrimidine derivatives 3 and 4 were evaluated against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) using the mycelium growth rate method. Some of them were effective in inhibiting the growth of the five phytopathogenic fungi. For instance, 6,7-diarylpyrazolo[1,5-a]pyrimidines (4j) inhibited the growth of A. solani with an [Formula: see text] value of 17.11 [Formula: see text], and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4h) inhibited the growth of both Cytospora sp. and F. solani with [Formula: see text] values of 27.32 and 21.04 [Formula: see text], respectively. A chemoselective synthesis of 5,6-pyrazolo[1,5-a]pyrimidines 3 derivatives in excellent yields was performed under microwave irradiation and 6,7-pyrazolo[1,5-a]pyrimidines 4 were also prepared using heating method. The antifungal properties of 3 and 4 were tested against Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani.

  4. Designing Stable Antiparallel Coiled Coil Dimers

    Institute of Scientific and Technical Information of China (English)

    曾宪纲; 周海梦

    2001-01-01

    The history of antiparallel coiled coil dimer design is briefly reviewed and the main principles governing the successful designs are explained. They include analysis of the inter-subunit electrostatic repulsion for determining partners for dimerization and of the buried polar interaction for determining the relative orientation of the partners. A theory is proposed to explain the lack of antiparallel coiled coil homodimers in nature.

  5. Role of Rydberg states in the photostability of heterocyclic dimers: the case of pyrazole dimer.

    Science.gov (United States)

    Zilberg, Shmuel; Haas, Yehuda

    2012-11-26

    A new route for the nonradiative decay of photoexcited, H-bonded, nitrogen-containing, heterocyclic dimers is offered and exemplified by a study of the pyrazole dimer. In some of these systems the N(3s) Rydberg state is the lowest excited singlet state. This state is formed by direct light absorption or by nonradiative transition from the allowed ππ* state. An isomer of this Rydberg state is formed by H atom transfer to the other component of the dimer. The newly formed H-bonded radical pair is composed of two radicals (a H-adduct of pyrazole, a heterocyclic analogue of the NH(4) radical) and the pyrazolium π-radical. It is calculated to have a shallow local minimum and is the lowest point on the PES of the H-pyrazole/pyrazolium radical pair. This species can cross back to the ground state of the original dimer through a relatively small energy gap and compete with the H-atom loss channel, known for the monomer. In both Rydberg dimers, an electron occupies a Rydberg orbital centered mostly on one of the two components of the dimer. This Rydberg Center Shift (RCS) mechanism, proposed earlier (Zilberg, S.; Kahan, A.; Haas, Y. Phys. Chem. Chem. Phys. 2012, 14, 8836), leads to deactivation of the electronically excited dimer while keeping it intact. It, thus, may explain the high photostability of the pyrazole dimer as well as other heterocyclic dimers.

  6. Functional role of dimerization of human peptidylarginine deiminase 4 (PAD4.

    Directory of Open Access Journals (Sweden)

    Yi-Liang Liu

    Full Text Available Peptidylarginine deiminase 4 (PAD4 is a homodimeric enzyme that catalyzes Ca²⁺-dependent protein citrullination, which results in the conversion of arginine to citrulline. This paper demonstrates the functional role of dimerization in the regulation of PAD4 activity. To address this question, we created a series of dimer interface mutants of PAD4. The residues Arg8, Tyr237, Asp273, Glu281, Tyr435, Arg544 and Asp547, which are located at the dimer interface, were mutated to disturb the dimer organization of PAD4. Sedimentation velocity experiments were performed to investigate the changes in the quaternary structures and the dissociation constants (K(d between wild-type and mutant PAD4 monomers and dimers. The kinetic data indicated that disrupting the dimer interface of the enzyme decreases its enzymatic activity and calcium-binding cooperativity. The K(d values of some PAD4 mutants were much higher than that of the wild-type (WT protein (0.45 µM and were concomitant with lower k(cat values than that of WT (13.4 s⁻¹. The K(d values of the monomeric PAD4 mutants ranged from 16.8 to 45.6 µM, and the k(cat values of the monomeric mutants ranged from 3.3 to 7.3 s⁻¹. The k(cat values of these interface mutants decreased as the K(d values increased, which suggests that the dissociation of dimers to monomers considerably influences the activity of the enzyme. Although dissociation of the enzyme reduces the activity of the enzyme, monomeric PAD4 is still active but does not display cooperative calcium binding. The ionic interaction between Arg8 and Asp547 and the Tyr435-mediated hydrophobic interaction are determinants of PAD4 dimer formation.

  7. On the gas-phase dimerization of negatively charged closo-dodecaborates: a theoretical study.

    Science.gov (United States)

    Zeonjuk, Lei Liu; Vankova, Nina; Knapp, Carsten; Gabel, Detlef; Heine, Thomas

    2013-07-07

    We have studied the intriguing gas-phase dimerization of the B12In(-) (n = 9, 8) anions to B24I2n(2-) dianions by means of density functional theory calculations. The dimerization of B12I9(-) to B24I18(2-) has been detected experimentally in a previous study (Phys. Chem. Chem. Phys., 2011, 13, 5712) utilizing electrospray ionization ion trap mass spectrometry (ESI-IT-MS), whereas the formation of B24I16(2-) from B12I8(-) is modeled here prior to experiment. Calculations are carried out to determine the molecular and electronic structures, the bonding situation and the stability of the dimers relative to the respective monomers. The dimerization process is found to be thermodynamically favorable, and the stability of the lowest-energy structures is substantiated by molecular dynamics simulations. The calculations imply that the experimentally observed B24I18(2-) and the hypothetical B24I16(2-) species are formed through dimerization of the respective B12In(-) (n = 9, 8) monomers, rather than through loss of two I radicals from B24I2n+2(2-) dimers. Electronic properties such as natural charges, vertical detachment energies (VDEs), frontier molecular orbitals (FMOs), and HOMO-LUMO gaps are computed and analyzed in detail for all monomers and dimers. The analysis shows that the most stable B24I2n(2-) dimers are formed through two 2c-2e B-B and two 3c-2e B-I-B bridges between the parent B12In(-) (n = 9, 8) monomers. These new bridging bonds engage the deiodinated (bare) faces of the two B12 icosahedra, as well as one (per monomer) of the nearest boron neighbors and its iodine substituent.

  8. Substrate-Induced Dimerization of Engineered Monomeric Variants of Triosephosphate Isomerase from Trichomonas vaginalis.

    Directory of Open Access Journals (Sweden)

    Samuel Lara-Gonzalez

    Full Text Available The dimeric nature of triosephosphate isomerases (TIMs is maintained by an extensive surface area interface of more than 1600 Å2. TIMs from Trichomonas vaginalis (TvTIM are held in their dimeric state by two mechanisms: a ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.

  9. Dynamic interplay between adhesive and lateral E-cadherin dimers

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Laur, Oscar Y; Troyanovsky, Regina B;

    2002-01-01

    M. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime...

  10. De novo pyrimidine biosynthesis in the oomycete plant pathogen Phytophthora infestans.

    Science.gov (United States)

    García-Bayona, Leonor; Garavito, Manuel F; Lozano, Gabriel L; Vasquez, Juan J; Myers, Kevin; Fry, William E; Bernal, Adriana; Zimmermann, Barbara H; Restrepo, Silvia

    2014-03-10

    The oomycete Phytophthora infestans, causal agent of the tomato and potato late blight, generates important economic and environmental losses worldwide. As current control strategies are becoming less effective, there is a need for studies on oomycete metabolism to help identify promising and more effective targets for chemical control. The pyrimidine pathways are attractive metabolic targets to combat tumors, virus and parasitic diseases but have not yet been studied in Phytophthora. Pyrimidines are involved in several critical cellular processes and play structural, metabolic and regulatory functions. Here, we used genomic and transcriptomic information to survey the pyrimidine metabolism during the P. infestans life cycle. After assessing the putative gene machinery for pyrimidine salvage and de novo synthesis, we inferred genealogies for each enzymatic domain in the latter pathway, which displayed a mosaic origin. The last two enzymes of the pathway, orotate phosphoribosyltransferase and orotidine-5-monophosphate decarboxylase, are fused in a multi-domain enzyme and are duplicated in some P. infestans strains. Two splice variants of the third gene (dihydroorotase) were identified, one of them encoding a premature stop codon generating a non-functional truncated protein. Relative expression profiles of pyrimidine biosynthesis genes were evaluated by qRT-PCR during infection in Solanum phureja. The third and fifth genes involved in this pathway showed high up-regulation during biotrophic stages and down-regulation during necrotrophy, whereas the uracil phosphoribosyl transferase gene involved in pyrimidine salvage showed the inverse behavior. These findings suggest the importance of de novo pyrimidine biosynthesis during the fast replicative early infection stages and highlight the dynamics of the metabolism associated with the hemibiotrophic life style of pathogen.

  11. N-(4-Meth-oxy-phen-yl)-6-methyl-2-phenyl-5-{[4-(tri-fluoro-meth-yl)anilino]meth-yl}pyrimidin-4-amine.

    Science.gov (United States)

    Cieplik, Jerzy; Pluta, Janusz; Bryndal, Iwona; Lis, Tadeusz

    2013-11-27

    The title compound, C26H23F3N4O, crystallizes with two symmetry-independent mol-ecules in the asymmetric unit, denoted A and B, which differ mainly in the rotation of the meth-oxy-phenyl ring. The -CF3 group of mol-ecule B is disordered by rotation, with the F atoms split over two sets of sites; the occupancy factor for the major component is 0.853 (4). The dihedral angles between the pyrimidine ring and the attached phenyl, meth-oxy-phenyl and tri-fluoro-methyl-phenyl rings are 8.1 (2), 37.5 (2) and 70.7 (2)°, respectively, in mol-ecule A, and 9.3 (2), 5.3 (2) and 79.7 (2)° in mol-ecule B. An intra-molecular N-H⋯N hydrogen bond occurs in each mol-ecule. In the crystal, two crystallographically independent mol-ecules associate into a dimer via a pair of N-H⋯N hydrogen bonds, with a resulting R 2 (2)(12) ring motif and π-π stacking inter-actions [centroid-centroid distance = 3.517 (4) Å] between the pyrimidine rings. For the A mol-ecules, there are inter-molecular C-H⋯O hydrogen bonds between an aryl C atom of meth-oxy-phenyl ring and a meth-oxy O atom of an adjacent mol-ecule. A similar inter-action is lacking in the B mol-ecules.

  12. Competitive Energy and Electron Transfer in β-Functionalized Free-Base Porphyrin-Zinc Porphyrin Dimer Axially Coordinated to C60 : Synthesis, Supramolecular Formation and Excited-State Processes.

    Science.gov (United States)

    Hu, Yi; Thomas, Michael B; Jinadasa, R G Waruna; Wang, Hong; D'Souza, Francis

    2017-09-18

    Simultaneous occurrence of energy and electron transfer events involving different acceptor sites in a newly assembled supramolecular triad comprised of covalently linked free-base porphyrin-zinc porphyrin dyad, H2 P-ZnP axially coordinated to electron acceptor fullerene, has been successfully demonstrated. The dyad was connected through the β-pyrrole positions of the porphyrin macrocycle instead of the traditionally used meso-positions for better electronic communication. Interestingly, the β-pyrrole functionalization modulated the optical properties to such an extent that it was possible to almost exclusively excite the zinc porphyrin entity in the supramolecular triad. The measured binding constant for the complex with 1:1 molecular stoichiometry was in the order of 10(4)  m(-1) revealing moderately stable complex formation. An energy level diagram constructed using optical, electrochemical and computational results suggested that both the anticipated energy and electron events are thermodynamically feasible in the triad. Consequently, it was possible to demonstrate occurrence of excited state energy transfer to the covalently linked H2 P, and electron transfer to the coordinated ImC60 from studies involving steady-state and time-resolved emission, and femto- and nanosecond transient absorption studies. The estimated energy transfer was around 67 % in the dyad with a rate constant of 1.1×10(9)  s(-1) . In the supramolecular triad, the charge separated state was rather long-lived although it was difficult to arrive the exact lifetime of charge separated state from nanosecond transient spectral studies due to overlap of strong triplet excited signals of porphyrin in the monitoring wavelength window. Nevertheless, simultaneous occurrence of energy and electron transfer in the appropriately positioned energy and electron acceptor entities in a supramolecular triad was possible to demonstrate in the present study, a step forward to unraveling the complex

  13. Coatomer and dimeric ADP ribosylation factor 1 promote distinct steps in membrane scission

    Science.gov (United States)

    Beck, Rainer; Prinz, Simone; Diestelkötter-Bachert, Petra; Röhling, Simone; Adolf, Frank; Hoehner, Kathrin; Welsch, Sonja; Ronchi, Paolo; Brügger, Britta

    2011-01-01

    Formation of coated vesicles requires two striking manipulations of the lipid bilayer. First, membrane curvature is induced to drive bud formation. Second, a scission reaction at the bud neck releases the vesicle. Using a reconstituted system for COPI vesicle formation from purified components, we find that a dimerization-deficient Arf1 mutant, which does not display the ability to modulate membrane curvature in vitro or to drive formation of coated vesicles, is able to recruit coatomer to allow formation of COPI-coated buds but does not support scission. Chemical cross-linking of this Arf1 mutant restores vesicle release. These experiments show that initial curvature of the bud is defined primarily by coatomer, whereas the membrane curvature modulating activity of dimeric Arf1 is required for membrane scission. PMID:21893600

  14. Fenarimol, a Pyrimidine-Type Fungicide, Inhibits Brassinosteroid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Keimei Oh

    2015-07-01

    Full Text Available The plant steroid hormone brassinosteroids (BRs are important signal mediators that regulate broad aspects of plant growth and development. With the discovery of brassinoazole (Brz, the first specific inhibitor of BR biosynthesis, several triazole-type BR biosynthesis inhibitors have been developed. In this article, we report that fenarimol (FM, a pyrimidine-type fungicide, exhibits potent inhibitory activity against BR biosynthesis. FM induces dwarfism and the open cotyledon phenotype of Arabidopsis seedlings in the dark. The IC50 value for FM to inhibit stem elongation of Arabidopsis seedlings grown in the dark was approximately 1.8 ± 0.2 μM. FM-induced dwarfism of Arabidopsis seedlings could be restored by brassinolide (BL but not by gibberellin (GA. Assessment of the target site of FM in BR biosynthesis by feeding BR biosynthesis intermediates indicated that FM interferes with the side chain hydroxylation of BR biosynthesis from campestanol to teasterone. Determination of the binding affinity of FM to purified recombinant CYP90D1 indicated that FM induced a typical type II binding spectrum with a Kd value of approximately 0.79 μM. Quantitative real-time PCR analysis of the expression level of the BR responsive gene in Arabidopsis seedlings indicated that FM induces the BR deficiency in Arabidopsis.

  15. Stabilization of sulfuric acid dimers by ammonia, methylamine, dimethylamine, and trimethylamine

    Science.gov (United States)

    Jen, Coty N.; McMurry, Peter H.; Hanson, David R.

    2014-06-01

    This study experimentally explores how ammonia (NH3), methylamine (MA), dimethylamine (DMA), and trimethylamine (TMA) affect the chemical formation mechanisms of electrically neutral clusters that contain two sulfuric acid molecules (dimers). Dimers may also contain undetectable compounds, such as water or bases, that evaporate upon ionization and sampling. Measurements were conducted using a glass flow reactor which contained a steady flow of humidified nitrogen with sulfuric acid concentrations of 107 to 109 cm-3. A known molar flow rate of a basic gas was injected into the flow reactor. The University of Minnesota Cluster Chemical Ionization Mass Spectrometer was used to measure the resulting sulfuric acid vapor and cluster concentrations. It was found that, for a given concentration of sulfuric acid vapor, the dimer concentration increases with increasing concentration of the basic gas, eventually reaching a plateau. The base concentrations at which the dimer concentrations saturate suggest NH3 < MA < TMA ≲ DMA in forming stabilized sulfuric acid dimers. Two heuristic models for cluster formation by acid-base reactions are developed to interpret the data. The models provide ranges of evaporation rate constants that are consistent with observations and leads to an analytic expression for nucleation rates that is consistent with atmospheric observations.

  16. CtBP1/BARS Gly172-->Glu mutant structure: impairing NAD(H)-binding and dimerization.

    Science.gov (United States)

    Nardini, Marco; Valente, Carmen; Ricagno, Stefano; Luini, Alberto; Corda, Daniela; Bolognesi, Martino

    2009-03-27

    C-terminal binding proteins (CtBPs) are multi-functional proteins involved in nuclear transcriptional co-repression, Golgi membrane fission, and synaptic ribbon formation. Binding of NAD(H) to CtBPs promotes dimerization. CtBP dimers act as a scaffold for multimeric protein complex formation, thus bridging transcriptional repressors and their targets in the nucleus. Based on size-exclusion chromatography experiments and on the crystal structure of the NAD(H)-free G172E CtBP mutant, we show here that absence of NAD(H) induces flexibility/backbone conformational changes at the dimerization interface and at the CtBP interdomain region. The results presented shed first light on the correlation between NAD(H)-binding and functional CtBP dimerization.

  17. Solvent Effects on the Monomer/Hydrogen-Bonded Dimer Equilibrium in Carboxylic Acids: (+)-(S)-Ketopinic Acid as a Case Study.

    Science.gov (United States)

    Rodríguez Ortega, Pilar Gema; Montejo Gámez, Manuel; Márquez López, Fernando; López González, Juan Jesús

    2016-06-21

    The hydrogen-bond-assisted self-association process of a chiral semirigid carboxylic acid, namely, (+)-(S)-ketopinic acid, has been studied. The multiconformational monomer/dimer equilibrium has been evaluated by means of a concentration-dependent FTIR study that enabled the experimental equilibrium constants of the dimer formation reaction (Kdim ) to be determined in two solvents of different polarity. In CDCl3 , dimeric forms predominate, even in diluted solutions (KdimCF =5.074), whereas in CD3 CN the self-association process is hindered and monomers are always the main species, irrespective of solute concentration (KdimAN =0.194). The reliability of the dimerization constants and the derived mono- and dimeric experimental fractions have been proven by means of accurate matching between the experimental vibrational circular dichroism spectra of the species and the theoretical spectra generated by considering the simultaneous weighted contributions of the concomitant monomers and dimers.

  18. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...

  19. Calix[4]arene supported clusters: a dimer of [Mn(III)Mn(II)] dimers

    DEFF Research Database (Denmark)

    Taylor, Stephanie M; McIntosh, Ruaraidh D; Beavers, Christine M;

    2011-01-01

    Phosphinate ligands allow for the transformation of a calix[4]arene supported [Mn(III)(2)Mn(II)(2)] tetramer cluster motif into an unusual [Mn(III)Mn(II)](2) dimer of dimers; the clusters self-assemble in the crystal to form bi-layer arrays reminiscent of the typical packing of calixarene solvates....

  20. Lead optimization through VLAK protocol: new annelated pyrrolo-pyrimidine derivatives as antitumor agents.

    Science.gov (United States)

    Lauria, Antonino; Patella, Chiara; Abbate, Ilenia; Martorana, Annamaria; Almerico, Anna Maria

    2012-09-01

    The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line resulted the most sensitive (pGI(50) = 6.68). Moreover the derivative 7-(3-Chloropropyl)-9-methyl-5-(methylsulfanyl)-8-phenyl-3H-imidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-2(7H)-one showed a good antitumor activity against the leukemia subpanel with a low cytotoxic activity, above all against the HCT11 human tumour cell line. The VLAK protocol revealed a good method to design new molecules with good antitumor activity, starting from low active compounds. Moreover this protocol focused on the pyrrolo-pyrimidine derivatives as useful starting point for further development to obtain more potent antitumor agents.

  1. Synthesis, crystal structure, characterization and antifungal activity of pyrazolo[1,5-a]pyrimidines derivatives

    Science.gov (United States)

    Zhang, Jin; Peng, Ju-Fang; Wang, Tao; Wang, Ping; Zhang, Zun-Ting

    2016-09-01

    Under microwave radiation, isomers 2-(pyrazolo[1,5-a]pyrimidin-5-yl)phenols (3) and 2-(pyrazolo[1,5-a]pyrimidin-7-yl)phenols (4) were simultaneously obtained by the condensation of chromones and 3-aminopyrazoles. These two isomers were fully characterized by IR, 1H NMR, 13C NMR and HRMS. In addition, a representative product 5-chloro-2-(2-methyl-pyrazolo[1,5-a] pyrimidin-5-yl)phenol (3e) was further conformed by the single crystal X-ray diffraction. The antifungal abilities of the obtained products 3 and 4 were evaluated against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani and Fusarium solani). The results revealed that 2-(pyrazolo[1,5-a]pyrimidin-5-yl)phenol (3a) and 4-chloro-2-(2-methylpyrazolo[1,5-a]pyrimidin-7-yl)phenol (4e) exhibited good antifungal abilities against Colletotrichum gloeosporioides with the IC50 values of 24.90 and 28.28 μg/mL, respectively.

  2. Divergent prebiotic synthesis of pyrimidine and 8-oxo-purine ribonucleotides

    Science.gov (United States)

    Stairs, Shaun; Nikmal, Arif; Bučar, Dejan-Krešimir; Zheng, Shao-Liang; Szostak, Jack W.; Powner, Matthew W.

    2017-05-01

    Understanding prebiotic nucleotide synthesis is a long standing challenge thought to be essential to elucidating the origins of life on Earth. Recently, remarkable progress has been made, but to date all proposed syntheses account separately for the pyrimidine and purine ribonucleotides; no divergent synthesis from common precursors has been proposed. Moreover, the prebiotic syntheses of pyrimidine and purine nucleotides that have been demonstrated operate under mutually incompatible conditions. Here, we tackle this mutual incompatibility by recognizing that the 8-oxo-purines share an underlying generational parity with the pyrimidine nucleotides. We present a divergent synthesis of pyrimidine and 8-oxo-purine nucleotides starting from a common prebiotic precursor that yields the β-ribo-stereochemistry found in the sugar phosphate backbone of biological nucleic acids. The generational relationship between pyrimidine and 8-oxo-purine nucleotides suggests that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids prior to the emergence of the canonical nucleotides of biology.

  3. HIV-1 DIS stem loop forms an obligatory bent kissing intermediate in the dimerization pathway.

    Science.gov (United States)

    Mundigala, Hansini; Michaux, Jonathan B; Feig, Andrew L; Ennifar, Eric; Rueda, David

    2014-06-01

    The HIV-1 dimerization initiation sequence (DIS) is a conserved palindrome in the apical loop of a conserved hairpin motif in the 5'-untranslated region of its RNA genome. DIS hairpin plays an important role in genome dimerization by forming a 'kissing complex' between two complementary hairpins. Understanding the kinetics of this interaction is key to exploiting DIS as a possible human immunodeficiency virus (HIV) drug target. Here, we present a single-molecule Förster resonance energy transfer (smFRET) study of the dimerization reaction kinetics. Our data show the real-time formation and dissociation dynamics of individual kissing complexes, as well as the formation of the mature extended duplex complex that is ultimately required for virion packaging. Interestingly, the single-molecule trajectories reveal the presence of a previously unobserved bent intermediate required for extended duplex formation. The universally conserved A272 is essential for the formation of this intermediate, which is stabilized by Mg(2+), but not by K(+) cations. We propose a 3D model of a possible bent intermediate and a minimal dimerization pathway consisting of three steps with two obligatory intermediates (kissing complex and bent intermediate) and driven by Mg(2+) ions. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Molecular interaction of the first 3 enzymes of the de novo pyrimidine biosynthetic pathway of Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Nara, Takeshi, E-mail: tnara@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Hashimoto, Muneaki; Hirawake, Hiroko [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Liao, Chien-Wei [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Parasitology, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan, ROC (China); Fukai, Yoshihisa; Suzuki, Shigeo; Tsubouchi, Akiko; Morales, Jorge; Takamiya, Shinzaburo [Department of Molecular and Cellular Parasitology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko [Division of Proteomics and Biomolecular Science, Biomedical Research Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Fan, Chia-Kwung [Department of Parasitology, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan, ROC (China); Inaoka, Daniel Ken [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Inoue, Masayuki [Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Tanaka, Akiko [Systems and Structural Biology Center, RIKEN, Tsurumi, Yokohama 230-0045 (Japan); Harada, Shigeharu [Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Kita, Kiyoshi [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); and others

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer An Escherichia coli strain co-expressing CPSII, ATC, and DHO of Trypanosoma cruzi was constructed. Black-Right-Pointing-Pointer Molecular interactions between CPSII, ATC, and DHO of T. cruzi were demonstrated. Black-Right-Pointing-Pointer CPSII bound with both ATC and DHO. Black-Right-Pointing-Pointer ATC bound with both CPSII and DHO. Black-Right-Pointing-Pointer A functional tri-enzyme complex might precede the establishment of the fused enzyme. -- Abstract: The first 3 reaction steps of the de novo pyrimidine biosynthetic pathway are catalyzed by carbamoyl-phosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), respectively. In eukaryotes, these enzymes are structurally classified into 2 types: (1) a CPSII-DHO-ATC fusion enzyme (CAD) found in animals, fungi, and amoebozoa, and (2) stand-alone enzymes found in plants and the protist groups. In the present study, we demonstrate direct intermolecular interactions between CPSII, ATC, and DHO of the parasitic protist Trypanosoma cruzi, which is the causative agent of Chagas disease. The 3 enzymes were expressed in a bacterial expression system and their interactions were examined. Immunoprecipitation using an antibody specific for each enzyme coupled with Western blotting-based detection using antibodies for the counterpart enzymes showed co-precipitation of all 3 enzymes. From an evolutionary viewpoint, the formation of a functional tri-enzyme complex may have preceded-and led to-gene fusion to produce the CAD protein. This is the first report to demonstrate the structural basis of these 3 enzymes as a model of CAD. Moreover, in conjunction with the essentiality of de novo pyrimidine biosynthesis in the parasite, our findings provide a rationale for new strategies for developing drugs for Chagas disease, which target the intermolecular interactions of these 3 enzymes.

  5. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    Directory of Open Access Journals (Sweden)

    Hardy Simon P

    2009-07-01

    Full Text Available Abstract Background The genomic fractions of purine (RR and alternating pyrimidine/purine (YR stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors are a consequence of the chemical properties of purines and pyrimidines, a thorough statistical examination of the distributions of YR/RR stretches in sequenced prokaryotic chromosomes has to the best of our knowledge, not been undertaken. The aim of this study is to expand upon previous research by using regression analysis to investigate how AT content, habitat, growth temperature, pathogenicity, phyla, oxygen requirement and halotolerance correlated with the distribution of RR and YR stretches in prokaryotes. Results Our results indicate that RR and YR-stretches are differently distributed in prokaryotic phyla. RR stretches are overrepresented in all phyla except for the Actinobacteria and β-Proteobacteria. In contrast, YR tracts are underrepresented in all phyla except for the β-Proteobacterial group. YR-stretches are associated with phylum, pathogenicity and habitat, whilst RR-tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p . Conclusion Analysis of chromosomal distributions of RR/YR sequences in prokaryotes reveals a set of associations with environmental factors not observed with mono- and oligonucleotide frequencies. This implies that important information can be found in the distribution of RR/YR stretches that is more difficult to obtain from genomic mono- and oligonucleotide frequencies. The association between pathogenicity and fractions of YR stretches is assumed to be linked to recombination and horizontal transfer.

  6. Dimerization of human lysyl hydroxylase 3 (LH3) is mediated by the amino acids 541-547.

    Science.gov (United States)

    Heikkinen, Jari; Risteli, Maija; Lampela, Outi; Alavesa, Paula; Karppinen, Marjo; Juffer, André H; Myllylä, Raili

    2011-01-01

    Lysyl hydroxylases (LH), which catalyze the post-translational modifications of lysines in collagen and collagen-like proteins, function as dimers. However, the amino acids responsible for dimerization and the role of dimer formation in the enzymatic activities of LH have not yet been identified. We have localized the region responsible for the dimerization of lysyl hydroxylase 3 (LH3), a multifunctional enzyme of collagen biosynthesis, to a sequence of amino acids between the glycosyltransferase activity and the lysyl hydroxylase activity domains. This area is covered by amino acids 541-547 in human LH3, but contains no cysteine residues. The region is highly conserved among LH isoforms, and is also involved in the dimerization of LH1 subunits. Dimerization is required for the LH activity of LH3, whereas it is not obligatory for the glycosyltransferase activities. In order to determine whether complex formation can occur between LH molecules originating from different species, and between different LH isoforms, double expressions were generated in a baculovirus system. Heterocomplex formation between mouse and human LH3, between human LH1 and LH3 and between human LH2 and LH3 was detected by western blot analyses. However, due to the low amount of complexes formed, the in vivo function of heterocomplexes remains unclear. Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  7. Adaptive Reprogramming of De Novo Pyrimidine Synthesis Is a Metabolic Vulnerability in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Brown, Kristin K; Spinelli, Jessica B; Asara, John M; Toker, Alex

    2017-04-01

    Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC), and strategies to circumvent resistance are required. Using in vitro and in vivo metabolic profiling of TNBC cells, we show that an increase in the abundance of pyrimidine nucleotides occurs in response to chemotherapy exposure. Mechanistically, elevation of pyrimidine nucleotides induced by chemotherapy is dependent on increased activity of the de novo pyrimidine synthesis pathway. Pharmacologic inhibition of de novo pyrimidine synthesis sensitizes TNBC cells to genotoxic chemotherapy agents by exacerbating DNA damage. Moreover, combined treatment with doxorubicin and leflunomide, a clinically approved inhibitor of the de novo pyrimidine synthesis pathway, induces regression of TNBC xenografts. Thus, the increase in pyrimidine nucleotide levels observed following chemotherapy exposure represents a metabolic vulnerability that can be exploited to enhance the efficacy of chemotherapy for the treatment of TNBC.Significance: The prognosis for patients with TNBC with residual disease after chemotherapy is poor. We find that chemotherapy agents induce adaptive reprogramming of de novo pyrimidine synthesis and show that this response can be exploited pharmacologically, using clinically approved inhibitors of de novo pyrimidine synthesis, to sensitize TNBC cells to chemotherapy. Cancer Discov; 7(4); 391-9. ©2017 AACR.See related article by Mathur et al., p. 380This article is highlighted in the In This Issue feature, p. 339.

  8. Substrate specificity of pyrimidine nucleoside phosphorylases of NP-II family probed by X-ray crystallography and molecular modeling

    Science.gov (United States)

    Balaev, V. V.; Lashkov, A. A.; Prokofev, I. I.; Gabdulkhakov, A. G.; Seregina, T. A.; Mironov, A. S.; Betzel, C.; Mikhailov, A. M.

    2016-09-01

    Pyrimidine nucleoside phosphorylases, which are widely used in the biotechnological production of nucleosides, have different substrate specificity for pyrimidine nucleosides. An interesting feature of these enzymes is that the three-dimensional structure of thymidine-specific nucleoside phosphorylase is similar to the structure of nonspecific pyrimidine nucleoside phosphorylase. The three-dimensional structures of thymidine phosphorylase from Salmonella typhimurium and nonspecific pyrimidine nucleoside phosphorylase from Bacillus subtilis in complexes with a sulfate anion were determined for the first time by X-ray crystallography. An analysis of the structural differences between these enzymes demonstrated that Lys108, which is involved in the phosphate binding in pyrimidine nucleoside phosphorylase, corresponds to Met111 in thymidine phosphorylases. This difference results in a decrease in the charge on one of the hydroxyl oxygens of the phosphate anion in thymidine phosphorylase and facilitates the catalysis through SN2 nucleophilic substitution. Based on the results of X-ray crystallography, the virtual screening was performed for identifying a potent inhibitor (anticancer agent) of nonspecific pyrimidine nucleoside phosphorylase, which does not bind to thymidine phosphorylase. The molecular dynamics simulation revealed the stable binding of the discovered compound—2-pyrimidin-2-yl-1H-imidazole-4-carboxylic acid—to the active site of pyrimidine nucleoside phosphorylase.

  9. Dominant role of the 5' TAR bulge in dimerization of HIV-1 genomic RNA, but no evidence of TAR-TAR kissing during in vivo virus assembly.

    Science.gov (United States)

    Jalalirad, Mohammad; Saadatmand, Jenan; Laughrea, Michael

    2012-05-08

    The 5' untranslated region of HIV-1 genomic RNA (gRNA) contains two stem-loop structures that appear to be equally important for gRNA dimerization: the 57-nucleotide 5' TAR, at the very 5' end, and the 35-nucleotide SL1 (nucleotides 243-277). SL1 is well-known for containing the dimerization initiation site (DIS) in its apical loop. The DIS is a six-nucleotide palindrome. Here, we investigated the mechanism of TAR-directed gRNA dimerization. We found that the trinucleotide bulge (UCU24) of the 5' TAR has dominant impacts on both formation of HIV-1 RNA dimers and maturation of the formed dimers. The ΔUCU trinucleotide deletion strongly inhibited the first process and blocked the other, thus impairing gRNA dimerization as severely as deletion of the entire 5' TAR, and more severely than deletion of the DIS, inactivation of the viral protease, or most severe mutations in the nucleocapsid protein. The apical loop of TAR contains a 10-nucleotide palindrome that has been postulated to stimulate gRNA dimerization by a TAR-TAR kissing mechanism analogous to the one used by SL1 to stimulate dimerization. Using mutations that strongly destabilize formation of the TAR palindrome duplex, as well as compensatory mutations that restore duplex formation to a wild-type-like level, we found no evidence of TAR-TAR kissing, even though mutations nullifying the kissing potential of the TAR palindrome could impair dimerization by a mechanism other than hindering of SL1. However, nullifying the kissing potential of TAR had much less severe effects than ΔUCU. By not uncovering a dimerization mechanism intrinsic to TAR, our data suggest that TAR mutations exert their effect 3' of TAR, yet not on SL1, because TAR and SL1 mutations have synergistic effects on gRNA dimerization.

  10. Accumulation of the Cyclobutane Thymine Dimer in Defined Sequences of Free and Nucleosomal DNA

    Science.gov (United States)

    2013-08-01

    suppresses thymine dimerization in a helix .19,20 Along tracts of (dT)n/(dA)n, dimers seem to accumulate at the 3′-terminal dithymine when irradiated as a...may also reflect a minimal change in helix structure when free in solution versus assembled into a NCP. This possibility is consistent with pre- vious...of cyclobutane and ɞ-4> dipyrimidines formation in triple -stranded H-DNA, Biochemistry, 1991, 30, 7021–7026. 20 V. A. Malkov, V. N. Soyfer and M. D

  11. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome.

    Science.gov (United States)

    Chabosseau, Pauline; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Lambert, Sarah; Debatisse, Michelle; Brison, Olivier; Amor-Guéret, Mounira

    2011-06-28

    Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome. Features of this syndrome include a slowdown in replication speed, defective fork reactivation and high rates of sister chromatid exchange, with a general predisposition to cancer. Bloom syndrome is caused by mutations in the BLM gene encoding a RecQ helicase. Here we report that BLM deficiency is associated with a strong cytidine deaminase defect, leading to pyrimidine pool disequilibrium. In BLM-deficient cells, pyrimidine pool normalization leads to reduction of sister chromatid exchange frequency and is sufficient for full restoration of replication fork velocity but not the fork restart defect, thus identifying the part of the Bloom syndrome phenotype because of pyrimidine pool imbalance. This study provides new insights into the molecular basis of control of replication speed and the genetic instability associated with Bloom syndrome. Nucleotide pool disequilibrium could be a general phenomenon in a large spectrum of precancerous and cancer cells.

  12. Thiolated pyrimidine nucleotides may interfere thiol groups concentrated at lipid rafts of HIV-1 infected cells.

    Science.gov (United States)

    Kanizsai, Szilvia; Ongrádi, Joseph; Aradi, János; Nagy, Károly

    2014-12-01

    Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29. Selective cytotoxicity of thiolated pyrimidines on HIV-1 infected cells were observed. Results indicate that thiolated pyrimidine derivates may interfere with -SH (thiol) groups concentrated in lipid rafts of cell membrane and interacts HIV-1 infected (activated) cells resulting in a selective cytotoxicity of HIV-1 infected cells, and reducing HIV-1 entry.

  13. Transport of pyrimidine nucleosides in cells of Escherichia coli K 12.

    Science.gov (United States)

    Mygind, B; Munch-Petersen

    1975-11-15

    1. The transport of pyrimidine mucleosides into cells of Escherichis coli has been investigated in mutant strains which cannot metabolize these nucleosides. Such cells transport and concentrate purimidine mucleosides several hindredfold. 2. The transport is inhibited by energy poisons and by sulfhydryl reagents. 3. Pyrimidine mucleosides compete mutually for transport. Adenosine is also a strong competitor while guanosine and inosine are weak competitors. 4. The rate of pyrimidine mucleoside transport is shown to be under control of the cytR and deoR gene products, which are also known to regulate the synthesis of nucleoside-catabolizing enzymes. The transport system is repressed by growth on glucose, as is the synthesis of the enzymes.

  14. Microwave assisted synthesis and antimicrobial activity of some novel pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    S. J. VAGHASIA

    2007-02-01

    Full Text Available The synthesis of thiazolo [5,4-d]pyrimidines can be achieved from different 5-thiazolidinones, 2-butyl-1H-imidazole-5-carbaldehyde and thiourea using microwave irradiation within 5 min. The structures of the products were supported by FTIR, PMR and mass spectral data. The in vitro antimicrobial activity of the synthesized thiazolo [5,4-d]pyrimidines 1a-j, having substituents at the 1- and 3-positions, were determined by the cup-plate method against several standard strains chosen to define the spectrum and potency of the new compounds. The antimicrobial activities of the thiazolo [5,4-d]pyrimidines 1a-j are compared with those of known chosen standard drugs, viz. ampicillin, chloramphenicol, ciprofloxacin, norfloxacin and griseofulvin.

  15. Synthesis and Antimicrobial Studies of Pyrimidine Pyrazole Heterocycles

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2014-01-01

    Full Text Available Prompted from the diversity of the wider use and being an integral part of genetic material, an effort was made to synthesize pyrimidine pyrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with satisfactory yield and purity. A novel series of 1,3-dimethyl-6-hydroxy-2,4-dioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl-1,2,3,4-tetrahydropyrimidines (5a–d and 1,3-diaryl-6-hydroxy-4-oxo-2-thioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl-1,2,3,4-tetrahydropyrimidines (5e–l has been synthesized. The structures of these compounds were established on the basis of FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. All the synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. Among all the compounds, 5g was found to be the most active as its MIC was 31.25 µg/mL against S. aureus and B. cereus. The compounds 5h, 5c, and 5e also possess antibacterial activity with MIC values as 62.50, 125.00, and 500.00 µg/mL, respectively. The compounds 5c and 5j were found to have antifungal activity against Aspergillus spp. As antifungal drugs lag behind the antibacterial drugs, therefore we tried in vitro combination of these two compounds with standard antifungal drugs (polyene and azole against Aspergillus spp. The combination of ketoconazole with 5c and 5j showed synergy at 1 : 8 (6.25 : 50.00 µg/mL and 1 : 4 (25 : 100 µg/mL against A. fumigatus (ITCC 4517 and A. fumigatus (VPCI 190/96, respectively.

  16. Ethyl 6-methyl-2-sulfanyl-idene-4-[4-(trifluoro-meth-yl)phen-yl]-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

    Science.gov (United States)

    Nayak, Susanta K; Venugopala, K N; Govender, Thavendran; Kruger, Hendrik G; Maguire, Glenn E M; Row, T N Guru

    2011-07-01

    The title compound, C(15)H(15)F(3)N(2)O(2)S, adopts a conformation with an intra-molecular C-H⋯π inter-action. The dihedral angles between the planes of the 4-(trifluoro-meth-yl)phenyl and ester groups with the plane of the six-membered tetra-hydro-pyrimidine ring are 81.8 (1) and 16.0 (1)°, respectively. In the crystal structure, inter-molecular N-H⋯S hydrogen bonds link pairs of mol-ecules into dimers and N-H⋯O inter-actions generate hydrogen-bonded mol-ecular chains along the crystallographic a axis.

  17. An expeditious four-component domino protocol for the synthesis of novel thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidine derivatives as antibacterial and antibiofilm agents.

    Science.gov (United States)

    Suresh, Lingala; Sagar Vijay Kumar, P; Poornachandra, Y; Ganesh Kumar, C; Babu, Nanubolu Jagadeesh; Chandramouli, G V P

    2016-08-15

    An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via [Bmim]HSO4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5H)-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular NH bond activation followed by CS bond formation leading to highly functionalized thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidines. The ionic liquid operates efficiently under mild conditions. The recyclability and scope for recovery of the ionic liquid makes this protocol environmentally benign. Further, the compounds 5d, 5g and 5k showed promising antimicrobial activity against the tested Gram-positive bacterial strains. Among them, the compound 5d was identified as a lead molecule exhibiting promising anti-biofilm activity towards Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with IC50 values of 2.1, 1.9, 2.4 and 5.3μg/mL, respectively. Further, the compound 5d showed increased levels of intracellular ROS accumulation in Staphylococcus aureus MTCC 96 suggesting that oxidative stress resulted in bacterial cell lysis and death.

  18. Structure and dimerization of translation initiation factor aIF5B in solution

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Louise Caroe Vohlander [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark); Oliveira, Cristiano Luis Pinto [Department of Chemistry, Centre for mRNP Biogenesis and Metabolism, and iNANO Interdisciplinary Nanoscience Center, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C (Denmark); Byron, Olwyn [Glasgow Biomedical Research Center, University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Jensen, Janni Mosgaard [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark); Pedersen, Jan Skov [Department of Chemistry, Centre for mRNP Biogenesis and Metabolism, and iNANO Interdisciplinary Nanoscience Center, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C (Denmark); Sperling-Petersen, Hans Uffe [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark); Mortensen, Kim Kusk, E-mail: kkm@science.au.dk [Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10, DK-8000 Aarhus C (Denmark)

    2011-12-09

    and a maximum dimension of {approx}130 A. The effects of glycerol on the formation of dimers are discussed. This new model of aIF5B in solution shows that there are universal structural differences between aIF5B and the homologous protein IF2 from Escherichia coli.

  19. Geometric Reid's recipe for dimer models

    CERN Document Server

    Bocklandt, Raf; Velez, Alexander Quintero

    2013-01-01

    Crepant resolutions of three-dimensional toric Gorenstein singularities are derived equivalent to noncommutative algebras arising from consistent dimer models. By choosing a special stability parameter and hence a distinguished crepant resolution $Y$, this derived equivalence generalises the Fourier-Mukai transform relating the $G$-Hilbert scheme and the skew group algebra $\\CC[x,y,z]\\ast G$ for a finite abelian subgroup of $\\SL(3,\\CC)$. We show that this equivalence sends the vertex simples to pure sheaves, except for the zero vertex which is mapped to the dualising complex of the compact exceptional locus. This generalises results of Cautis-Logvinenko and Cautis-Craw-Logvinenko to the dimer setting, though our approach is different in each case. We also describe some of these pure sheaves explicitly and compute the support of the remainder, providing a dimer model analogue of results from Logvinenko.

  20. Photoionization of helium dimers; Photoionisation von Heliumdimeren

    Energy Technology Data Exchange (ETDEWEB)

    Havermeier, Tilo

    2010-06-09

    The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

  1. Kosterlitz Thouless Universality in Dimer Models

    CERN Document Server

    Chandrasekharan, S; Chandrasekharan, Shailesh; Strouthos, Costas G.

    2003-01-01

    Using the monomer-dimer representation of strongly coupled U(N) lattice gauge theories with staggered fermions, we study finite temperature chiral phase transitions in (2+1) dimensions. A new cluster algorithm allows us to compute monomer-monomer and dimer-dimer correlations at zero monomer density (chiral limit) accurately on large lattices. This makes it possible to show convincingly, for the first time, that these models undergo a finite temperature phase transition which belongs to the Kosterlitz-Thouless universality class. We find that this universality class is unaffected even in the large N limit. This shows that the mean field analysis often used in this limit breaks down in the critical region.

  2. Poly[tetrakis(selenocyanato-κNbis(methanol-κOtris(μ-pyrimidine-κ2N:N′dicobalt(II

    Directory of Open Access Journals (Sweden)

    Mario Wriedt

    2010-07-01

    Full Text Available In the title compound, [Co2(NCSe4(C4H4N23(CH3OH2]n, the CoII ion is coordinated by three N-bonded pyrimidine ligands, two N-bonded selenocyanate anions and one O-bonded methanol molecule in an octahedral coordination mode. The asymmetric unit consists of one CoII ion, one pyrimidine ligand, two selenocyanate anions and one methanol molecule in general positions as well as one pyrimidine ligand located around a twofold rotation axis. In the crystal structure, the pyrimidine ligands bridge [Co(CNSe2(CH3OH] units into zigzag-like chains, which are further connected by pyrimidine ligands into layers parallel to (010.

  3. Breakdown of the regulatory control of pyrimidine biosynthesis in human breast cancer cells.

    Science.gov (United States)

    Sigoillot, Frederic D; Sigoillot, Severine M; Guy, Hedeel I

    2004-04-20

    The activity of the de novo pyrimidine biosynthetic pathway in the MCF7 breast cancer cells was 4.4-fold higher than that in normal MCF10A breast cells. Moreover, while pyrimidine biosynthesis in MCF10A was tightly regulated, increasing as the culture matured and subsequently down-regulated in confluency, the biosynthetic rate in MCF7 cells remained elevated and invariant in all growth phases. The flux through the pathway is regulated by carbamoyl phosphate synthetase, a component of the multifunctional protein, CAD. The intracellular CAD concentration was 3.5- to 4-fold higher in MCF7 cells, an observation that explains the high rate of pyrimidine biosynthesis but cannot account for the lack of growth-dependent regulation. In MCF10A cells, up-regulation of the pathway in the exponential growth phase resulted from MAP kinase phosphorylation of CAD Thr456. The pathway was subsequently down-regulated by dephosphorylation of P approximately Thr456 and the phosphorylation of CAD by PKA. In contrast, the CAD P approximately Thr456 was persistently phosphorylated in MCF7 cells, while the PKA site remained unphosphorylated and consequently the activity of the pathway was elevated in all growth phases. In support of this interpretation, inhibition of MAP kinase in MCF7 cells decreased CAD P approximately Thr456, increased PKA phosphorylation and decreased pyrimidine biosynthesis. Conversely, transfection of MCF10A with constructs that elevated MAP kinase activity increased CAD P approximately Thr456 and the pyrimidine biosynthetic rate. The differences in the CAD phosphorylation state responsible for unregulated pyrimidine biosynthesis in MCF7 cells are likely to be a consequence of the elevated MAP kinase activity and the antagonism between MAP kinase- and PKA-mediated phosphorylations.

  4. Erwinia amylovora pyrC mutant causes fire blight despite pyrimidine auxotrophy.

    Science.gov (United States)

    Ramos, L S; Sinn, J P; Lehman, B L; Pfeufer, E E; Peter, K A; McNellis, T W

    2015-06-01

    Erwinia amylovora bacteria cause fire blight disease, which affects apple and pear production worldwide. The Erw. amylovora pyrC gene encodes a predicted dihydroorotase enzyme involved in pyrimidine biosynthesis. Here, we discovered that the Erw. amylovora pyrC244::Tn5 mutant was a uracil auxotroph. Unexpectedly, the Erw. amylovora pyrC244::Tn5 mutant grew as well as the wild-type in detached immature apple and pear fruits. Fire blight symptoms caused by the pyrC244::Tn5 mutant in immature apple and pear fruits were attenuated compared to those caused by the wild-type. The pyrC244::Tn5 mutant also caused severe fire blight symptoms in apple tree shoots. A plasmid-borne copy of the wild-type pyrC gene restored prototrophy and symptom induction in apple and pear fruit to the pyrC244::Tn5 mutant. These results suggest that Erw. amylovora can obtain sufficient pyrimidine from the host to support bacterial growth and fire blight disease development, although de novo pyrimidine synthesis by Erw. amylovora is required for full symptom development in fruits. Significance and impact of the study: This study provides information about the fire blight host-pathogen interaction. Although the Erwinia amylovora pyrC mutant was strictly auxotrophic for pyrimidine, it grew as well as the wild-type in immature pear and apple fruits and caused severe fire blight disease in apple trees. This suggests that Erw. amylovora can obtain sufficient pyrimidines from host tissue to support growth and fire blight disease development. This situation contrasts with findings in some human bacterial pathogens, which require de novo pyrimidine synthesis for growth in host blood, for example.

  5. Ionization of cytosine monomer and dimer studied by VUV photoionization and electronic structure calculations

    Energy Technology Data Exchange (ETDEWEB)

    Kostko, Oleg; Bravaya, Ksenia; Krylov, Anna; Ahmed, Musahid

    2009-12-14

    We report a combined theoretical and experimental study of ionization of cytosine monomers and dimers. Gas-phase molecules are generated by thermal vaporization of cytosine followed by expansion of the vapor in a continuous supersonic jet seeded in Ar. The resulting species are investigated by single photon ionization with tunable vacuum-ultraviolet (VUV) synchrotron radiation and mass analyzed using reflectron mass spectrometry. Energy onsets for the measured photoionization efficiency (PIE) spectra are 8.60+-0.05 eV and 7.6+-0.1 eV for the monomer and the dimer, respectively, and provide an estimate for the adiabatic ionization energies (AIE). The first AIE and the ten lowest vertical ionization energies (VIEs) for selected isomers of cytosine dimer computed using equation-of-motion coupled-cluster (EOM-IP-CCSD) method are reported. The comparison of the computed VIEs with the derivative of the PIE spectra, suggests that multiple isomers of the cytosine dimer are present in the molecular beam. The calculations reveal that the large red shift (0.7 eV) of the first IE of the lowest-energy cytosine dimer is due to strong inter-fragment electrostatic interactions, i.e., the hole localized on one of the fragments is stabilized by the dipole moment of the other. A sharp rise in the CH+ signal at 9.20+-0.05 eV is ascribed to the formation of protonated cytosine by dissociation of the ionized dimers. The dominant role of this channel is supported by the computed energy thresholds for the CH+ appearance and the barrierless or nearly barrierless ionization-induced proton transfer observed for five isomers of the dimer.

  6. Photon Propagation through Linearly Active Dimers

    Directory of Open Access Journals (Sweden)

    José Delfino Huerta Morales

    2017-06-01

    Full Text Available We provide an analytic propagator for non-Hermitian dimers showing linear gain or losses in the quantum regime. In particular, we focus on experimentally feasible realizations of the PT -symmetric dimer and provide their mean photon number and second order two-point correlation. We study the propagation of vacuum, single photon spatially-separable, and two-photon spatially-entangled states. We show that each configuration produces a particular signature that might signal their possible uses as photon switches, semi-classical intensity-tunable sources, or spatially entangled sources to mention a few possible applications.

  7. Refined conformal spectra in the dimer model

    CERN Document Server

    Rasmussen, Jorgen

    2012-01-01

    Working with Lieb's transfer matrix for the dimer model, we point out that the full set of dimer configurations may be partitioned into disjoint subsets (sectors) closed under the action of the transfer matrix. These sectors are labelled by an integer or half-integer quantum number we call the variation index. In the continuum scaling limit, each sector gives rise to a representation of the Virasoro algebra. We determine the corresponding conformal partition functions and their finitizations, and observe an intriguing link to the Ramond and Neveu-Schwarz sectors of the critical dense polymer model as described by a conformal field theory with central charge c=-2.

  8. The use of pyr-mutations to modify pyrimidine pools in Lactococci

    DEFF Research Database (Denmark)

    Hansen, Steen Lyders Lerche; Martinussen, Jan; Hammer, Karin

    1999-01-01

    . By combining the two described mutations, with a cdd mutation, we will be able to construct strains in which pyrimidine pools can be manipulated by adding different pyrimidine-sources at variable concentrations to the growth media. Since nucleotides are central metabolites, many physiological parameters may......The specific engineering of organisms used for startercultures has become an effective way of improving and developing new products in the dairy industry. In order to obtain strains with specific characteristics, it is imperative to have a good understanding of the central biochemical pathways...

  9. The use of Pyr-mutants to modify pyrimidine metabolism in lactococci

    DEFF Research Database (Denmark)

    Hansen, Steen Lyders Lerche; Martinussen, Jan; Hammer, Karin

    1998-01-01

    . By combining the two described mutations, with a cdd mutation, we will be able to construct strains in which pyrimidine pools can be manipulated by adding different pyrimidine-sources at variable concentrations to the growth media. Since nucleotides are central metabolites, many physiological parameters may......The specific engineering of organisms used for startercultures has become an effective way of improving and developing new products in the dairy industry. In order to obtain strains with specific characteristics, it is imperative to have a good understanding of the central biochemical pathways...

  10. Design,Synthesis,and Hypnotic Activity of Pyrazolo[1,5-a]pyrimidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    Song Qing WANG; Lin FANG; Xiu Jie LIU; Kang ZHAO

    2004-01-01

    On the basis of the Zaleplon structure, novel pyrazolo[1,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity.This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate.The structures of the derived target compounds were confirmed by their IR and 1H-NMR spectroscopic data.The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, while derivative 1c was the most potent one.

  11. Heteroaryl ethers by oxidative palladium catalysis of pyridotriazol-1-yloxy pyrimidines with arylboronic acids.

    Science.gov (United States)

    Bardhan, Sujata; Wacharasindhu, Sumrit; Wan, Zhao-Kui; Mansour, Tarek S

    2009-06-18

    The oxidative palladium-catalyzed cross-coupling of pyrimidines containing pyridotriazol-1-yloxy (OPt) as either a urea or an amide functional group with arylboronic acids in the presence of Cs(2)CO(3) in DME containing 0.6-1.0% H(2)O is described for the preparation of heteroaryl ethers. The bromo substitution in the case of 3-(5-bromo-pyrimidin-2-yloxy)-3H-[1,2,3]triazolo[4,5-b]pyridine 1 could serve as a handle for further elaborations such as Suzuki coupling for attaching varied aryl groups.

  12. Design, synthesis and cytotoxic activity of some novel compounds containing pyrazolo[3,4-]pyrimidines nucleus

    Indian Academy of Sciences (India)

    Manal M Kandeel; Sameha M Roshdy; Eman K A Abdelall; Mohamed A Abdelgawad; Phoebe F Lamie

    2013-09-01

    Novel pyrazolo[3,4-]pyrimidines were designed and synthesized as antitumour agents against human breast cancer adenoma (MCF-7). Molecular modelling and pharmacological screening were performed against breast cancer cell line and also certain synthetic pathways were developed in order to introduce functionality onto C6 and N5 positions of pyrimidine moiety. Surprisingly, all the test compounds showed IC50 lower than that of the standard olomoucine I, especially compounds 4b, 8a, 10b, 11a and b, which showed IC50 between 0.009 and 0.004 M.

  13. Molecular Interplay between the Dimer Interface and the Substrate-Binding Site of Human Peptidylarginine Deiminase 4

    Science.gov (United States)

    Lee, Chien-Yun; Lin, Chu-Cheng; Liu, Yi-Liang; Liu, Guang-Yaw; Liu, Jyung-Hurng; Hung, Hui-Chih

    2017-01-01

    Our previous studies suggest that the fully active form of Peptidylarginine deiminase 4 (PAD4) should be a dimer and not a monomer. This paper provides a plausible mechanism for the control of PAD4 catalysis by molecular interplay between its dimer-interface loop (I-loop) and its substrate-binding loop (S-loop). Mutagenesis studies revealed that two hydrophobic residues, W347 and V469, are critical for substrate binding at the active site; mutating these two residues led to a severe reduction in the catalytic activity. We also identified several hydrophobic amino acid residues (L6, L279 and V283) at the dimer interface. Ultracentrifugation analysis revealed that interruption of the hydrophobicity of this region decreases dimer formation and, consequently, enzyme activity. Molecular dynamic simulations and mutagenesis studies suggested that the dimer interface and the substrate-binding site of PAD4, which consist of the I-loop and the S-loop, respectively, are responsible for substrate binding and dimer stabilization. We identified five residues with crucial roles in PAD4 catalysis and dimerization: Y435 and R441 in the I-loop, D465 and V469 in the S-loop, and W548, which stabilizes the I-loop via van der Waals interactions with C434 and Y435. The molecular interplay between the S-loop and the I-loop is crucial for PAD4 catalysis. PMID:28209966

  14. Molecular Interplay between the Dimer Interface and the Substrate-Binding Site of Human Peptidylarginine Deiminase 4.

    Science.gov (United States)

    Lee, Chien-Yun; Lin, Chu-Cheng; Liu, Yi-Liang; Liu, Guang-Yaw; Liu, Jyung-Hurng; Hung, Hui-Chih

    2017-02-17

    Our previous studies suggest that the fully active form of Peptidylarginine deiminase 4 (PAD4) should be a dimer and not a monomer. This paper provides a plausible mechanism for the control of PAD4 catalysis by molecular interplay between its dimer-interface loop (I-loop) and its substrate-binding loop (S-loop). Mutagenesis studies revealed that two hydrophobic residues, W347 and V469, are critical for substrate binding at the active site; mutating these two residues led to a severe reduction in the catalytic activity. We also identified several hydrophobic amino acid residues (L6, L279 and V283) at the dimer interface. Ultracentrifugation analysis revealed that interruption of the hydrophobicity of this region decreases dimer formation and, consequently, enzyme activity. Molecular dynamic simulations and mutagenesis studies suggested that the dimer interface and the substrate-binding site of PAD4, which consist of the I-loop and the S-loop, respectively, are responsible for substrate binding and dimer stabilization. We identified five residues with crucial roles in PAD4 catalysis and dimerization: Y435 and R441 in the I-loop, D465 and V469 in the S-loop, and W548, which stabilizes the I-loop via van der Waals interactions with C434 and Y435. The molecular interplay between the S-loop and the I-loop is crucial for PAD4 catalysis.

  15. Synthesis and Characterization of Tetrahydrofurfurylcyclopentadienyl Molybdenum Tricarbonyl Dimer: Evidence for 19-Electron Intramolecular "Solvento" Interactions.

    Science.gov (United States)

    Gallagher, Michelle; Dougherty, Pat; Tanner, Pamela S.; Barbini, Denis C.; Schulte, Jurgen; Jones, Wayne E.

    1999-06-14

    The synthesis and characterization of a THF pendant, dimeric Mo cyclopentadienyl complex is reported and the structure characterized by NMR, FTIR, and UV-vis spectroscopies. The dimer was found to undergo metal-metal bond homolysis under either photochemical or electrochemical conditions to yield an odd-electron complex. Cyclic voltammetry under varying scan rate conditions from 25 to 10 000 mV/s demonstrates a dynamic equilibrium process that we assign to the formation of either an intramolecular 19-electron (18 + delta) complex or a bare 17-electron complex. Photolysis of the dimer in room temperature solution could be monitored as a loss of the dpi-dsigma transition at 503 nm by transient absorption spectroscopy. The recovery of the transient absorption signal at 410 nm follows first-order kinetics at a rate of 5 x 10(3) s(-1).

  16. Observation and photophysical characterization of silicon phthalocyanine J-aggregate dimers in aqueous solutions.

    Science.gov (United States)

    Doane, Tennyson; Chomas, Andrew; Srinivasan, Shriya; Burda, Clemens

    2014-06-23

    The use of macrocyclic molecules for both imaging and photodynamic therapy (PDT) has proven to be a powerful method for assessing and treating diseases, respectively. However, many potential candidates for these applications rely on rigid organic structures which are hydrophobic and thus lead to possible aggregation in aqueous solutions such as blood. Here, we describe the discovery of noncovalent J-aggregate dimers of the asymmetrically, axially modified silicon phthalocyanine 4 (Pc 4) in aqueous solutions through steady-state and time-resolved spectroscopy. Remarkably, the monomer-dimer equilibrium is dictated by water content and pH, with free monomers resulting in favorable solvation conditions even after formation of the dimer complex. This work sheds light on previous observations of Pc 4 behavior in cells during PDT, and can further elucidate the structure-activity relationship of these important molecules.

  17. Molecular design principles underlying β-strand swapping in the adhesive dimerization of cadherins.

    Science.gov (United States)

    Vendome, Jeremie; Posy, Shoshana; Jin, Xiangshu; Bahna, Fabiana; Ahlsen, Goran; Shapiro, Lawrence; Honig, Barry

    2011-06-01

    Cell adhesion by classical cadherins is mediated by dimerization of their EC1 domains through the 'swapping' of N-terminal β-strands. We use molecular simulations, measurements of binding affinities and X-ray crystallography to provide a detailed picture of the structural and energetic factors that control the adhesive dimerization of cadherins. We show that strand swapping in EC1 is driven by conformational strain in cadherin monomers that arises from the anchoring of their short N-terminal strand at one end by the conserved Trp2 and at the other by ligation to Ca(2+) ions. We also demonstrate that a conserved proline-proline motif functions to avoid the formation of an overly tight interface where affinity differences between different cadherins, crucial at the cellular level, are lost. We use these findings to design site-directed mutations that transform a monomeric EC2-EC3 domain cadherin construct into a strand-swapped dimer.

  18. CT Findings of Disease with Elevated Serum D-Dimer Levels in an Emergency Room Setting

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Ji Youn; Kwon, Woo Cheol; Kim, Young Ju [Dept. of Radiology, Wonju Christian Hospital, Yensei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2012-01-15

    Pulmonary embolism and deep vein thrombosis are the leading causes of elevated serum D-dimer levels in the emergency room. Although D-dimer is a useful screening test because of its high sensitivity and negative predictive value, it has a low specificity. In addition, D-dimer can be elevated in various diseases. Therefore, information on the various diseases with elevated D-dimer levels and their radiologic findings may allow for accurate diagnosis and proper management. Herein, we report the CT findings of various diseases with elevated D-dimer levels in an emergency room setting, including an intravascular contrast filling defect with associated findings in a venous thromboembolism, fracture with soft tissue swelling and hematoma formation in a trauma patient, enlargement with contrast enhancement in the infected organ of a patient, coronary artery stenosis with a perfusion defect of the myocardium in a patient with acute myocardial infarction, high density of acute thrombus in a cerebral vessel with a low density of affected brain parenchyma in an acute cerebral infarction, intimal flap with two separated lumens in a case of aortic dissection, organ involvement of malignancy in a cancer patient, and atrophy of a liver with a dilated portal vein and associated findings.

  19. Synthesis and mesomorphism of diacetylene-bridged triphenylene discotic liquid crystal dimers

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Connecting two discotic mesogens via a spacer not only stabilizes the columnar mesophase but also leads to the formation of glass columnar phase, and therefore improves the physical properties of discotic liquid crystals as organic semiconductor. Here, we report the synthesis of eight diacetylene-bridged triphenylene discotic liquid crystal dimers, [C18H6(OCnH2n+1)4(OMe)O2C-C8H16-C≡≡ C-]2, 3(n), (n = 4-8), [C18H6(OC6H13)5O2C-C8H16-C≡≡ C-]2, 6 and [C18H6(OC6H13)5O-(CH2)m-C≡≡ C-]2, 8(m), (m = 1, 3) by Eglinton coupling reaction. The thermotropic liquid crystal properties were studied by differential scanning calorimetry and polarized optical microscopy. The results are showed as follows: the length of peripheral alkyl chains of triphenylene influenced properties of liquid crystal dimers; dimers 3(n) (n = 5-8) and 6 had glass columnar phase, and no crystallization was observed above -50℃ for all the triphenylene dimers; compared with 3(6), 6 showed higher molecular symmetry, more stable columnar mesophase and wider mesophase range. The connecting group, length and rigidity of spacer had important influence on the mesomorphism of diacetylene-bridged triphenylene discotic liquid crystal dimers.

  20. Kinetic analysis of histamine release due to covalently linked IgE dimers

    Energy Technology Data Exchange (ETDEWEB)

    Dembo, M. (Los Alamos Scientific Lab., NM); Kagey-Sobotka, A.; Lichtenstein, L.M.; Goldstein, B.

    1982-01-01

    We present a kinetic model of histamine release from human basophils due to covalently linked IgE dimers. Comparison of theory with experiment shows that the model gives a good description of histamine release by IgE dimers and allows a number of the parameters of the model to be determined. Comparison with previous models of release by conventional antigens indicates that despite their covalent structure, IgE dimers are subject to the same laws governing inactivation as are antigen produced crosslinks. In addition, the kinetic equation which relates the rate of histamine release to the number of crosslinked Fc/sub e/ receptors per cell is the same for crosslinks formed by IgE dimers as for antigen induced crosslinks. Quantitative fitting of histamine release data also yields a value for the rate constant for crosslink formation by IgE dimer on the cell surface (r/sub x/ approx. = to 5 x 10/sup -10/ cm/sup 2//sec). This rate constant is remarkably high and indicates that the reaction is diffusion controlled.

  1. Monoubiquitination and activity of the paracaspase MALT1 requires glutamate 549 in the dimerization interface.

    Directory of Open Access Journals (Sweden)

    Katrin Cabalzar

    Full Text Available The mucosa-associated lymphoid tissue protein-1 (MALT1, also known as paracaspase is a protease whose activity is essential for the activation of lymphocytes and the growth of cells derived from human diffuse large B-cell lymphomas of the activated B-cell subtype (ABC DLBCL. Crystallographic approaches have shown that MALT1 can form dimers via its protease domain, but why dimerization is relevant for the biological activity of MALT1 remains largely unknown. Using a molecular modeling approach, we predicted Glu 549 (E549 to be localized within the MALT1 dimer interface and thus potentially relevant. Experimental mutation of this residue into alanine (E549A led to a complete impairment of MALT1 proteolytic activity. This correlated with an impaired capacity of the mutant to form dimers of the protease domain in vitro, and a reduced capacity to promote NF-κB activation and transcription of the growth-promoting cytokine interleukin-2 in antigen receptor-stimulated lymphocytes. Moreover, this mutant could not rescue the growth of ABC DLBCL cell lines upon MALT1 silencing. Interestingly, the MALT1 mutant E549A was unable to undergo monoubiquitination, which we identified previously as a critical step in MALT1 activation. Collectively, these findings suggest a model in which E549 at the dimerization interface is required for the formation of the enzymatically active, monoubiquitinated form of MALT1.

  2. Monoubiquitination and activity of the paracaspase MALT1 requires glutamate 549 in the dimerization interface.

    Science.gov (United States)

    Cabalzar, Katrin; Pelzer, Christiane; Wolf, Annette; Lenz, Georg; Iwaszkiewicz, Justyna; Zoete, Vincent; Hailfinger, Stephan; Thome, Margot

    2013-01-01

    The mucosa-associated lymphoid tissue protein-1 (MALT1, also known as paracaspase) is a protease whose activity is essential for the activation of lymphocytes and the growth of cells derived from human diffuse large B-cell lymphomas of the activated B-cell subtype (ABC DLBCL). Crystallographic approaches have shown that MALT1 can form dimers via its protease domain, but why dimerization is relevant for the biological activity of MALT1 remains largely unknown. Using a molecular modeling approach, we predicted Glu 549 (E549) to be localized within the MALT1 dimer interface and thus potentially relevant. Experimental mutation of this residue into alanine (E549A) led to a complete impairment of MALT1 proteolytic activity. This correlated with an impaired capacity of the mutant to form dimers of the protease domain in vitro, and a reduced capacity to promote NF-κB activation and transcription of the growth-promoting cytokine interleukin-2 in antigen receptor-stimulated lymphocytes. Moreover, this mutant could not rescue the growth of ABC DLBCL cell lines upon MALT1 silencing. Interestingly, the MALT1 mutant E549A was unable to undergo monoubiquitination, which we identified previously as a critical step in MALT1 activation. Collectively, these findings suggest a model in which E549 at the dimerization interface is required for the formation of the enzymatically active, monoubiquitinated form of MALT1.

  3. Self-assembly in a model colloidal mixture of dimers and spherical particles

    Science.gov (United States)

    Prestipino, Santi; Munaò, Gianmarco; Costa, Dino; Caccamo, Carlo

    2017-02-01

    We investigate the structure of a dilute mixture of amphiphilic dimers and spherical particles, a model relevant to the problem of encapsulating globular "guest" molecules in a dispersion. Dimers and spheres are taken to be hard particles, with an additional attraction between spheres and the smaller monomers in a dimer. Using the Monte Carlo simulation, we document the low-temperature formation of aggregates of guests (clusters) held together by dimers, whose typical size and shape depend on the guest concentration χ. For low χ (less than 10%), most guests are isolated and coated with a layer of dimers. As χ progressively increases, clusters grow in size becoming more and more elongated and polydisperse; after reaching a shallow maximum for χ ≈50 % , the size of clusters again reduces upon increasing χ further. In one case only (χ =50 % and moderately low temperature) the mixture relaxed to a fluid of lamellae, suggesting that in this case clusters are metastable with respect to crystal-vapor separation. On heating, clusters shrink until eventually the system becomes homogeneous on all scales. On the other hand, as the mixture is made denser and denser at low temperature, clusters get increasingly larger until a percolating network is formed.

  4. Synthesis and mesomorphism of diacetylene-bridged triphenylene discotic liquid crystal dimers

    Institute of Scientific and Technical Information of China (English)

    JI Hong; ZHAO KeQing; YU WenHao; WANG BiQin; HU Pin

    2009-01-01

    Connecting two discotic mesogens via a spacer not only stabilizes the columnar mesophase but also leads to the formation of glass columnar phase,and therefore improves the physical properties of discotic liquid crystals as organic semiconductor.Here,we report the synthesis of eight diacetylene-bridged triphenylene discotic liquid crystal dimers,[C18H6(OCnH2n+1)4(OMe)O2C-CsH16-C≡C-]2,3(n),(n=4-8),[C18H6(OC6H13)5O2C-C8H16-C≡C-]2,6 and [C18H6(OC6H13)5O-(CH2)m-C≡C-]2,8(m),(m=1,3) by Eglinton coupling reaction.The thermotropic liquid crystal properties were studied by differential scanning calorimetry and polarized optical microscopy.The results are showed as follows:the length of peripheral alkyl chains of triphenylene influenced properties of liquid crystal dimers;dimers 3(n) (n=5-8) and 6 had glass columnar phase,and no crystallization was observed above -50℃ for all the triphenylene dimers;compared with 3(6),6 showed higher molecular symmetry,more stable columnar mesophase and wider mesophase range.The connecting group,length and rigidity of spacer had important influence on the mesomorphism of diacetylene-bridged triphenylene discotic liquid crystal dimers.

  5. Hepatitis C virus genomic RNA dimerization is mediated via a kissing complex intermediate

    Science.gov (United States)

    Shetty, Sumangala; Kim, Seungtaek; Shimakami, Tetsuro; Lemon, Stanley M.; Mihailescu, Mihaela-Rita

    2010-01-01

    With over 200 million people infected with hepatitis C virus (HCV) worldwide, there is a need for more effective and better-tolerated therapeutic strategies. The HCV genome is a positive-sense; single-stranded RNA encoding a large polyprotein cleaved at multiple sites to produce at least ten proteins, among them an error-prone RNA polymerase that confers a high mutation rate. Despite considerable overall sequence diversity, in the 3′-untranslated region of the HCV genomic RNA there is a 98-nucleotide (nt) sequence named X RNA, the first 55 nt of which (X55 RNA) are 100% conserved among all HCV strains. The X55 region has been suggested to be responsible for in vitro dimerization of the genomic RNA in the presence of the viral core protein, although the mechanism by which this occurs is unknown. In this study, we analyzed the X55 region and characterized the mechanism by which it mediates HCV genomic RNA dimerization. Similar to a mechanism proposed previously for the human immunodeficiency 1 virus (HIV-1) genome, we show that dimerization of the HCV genome involves formation of a kissing complex intermediate, which is converted to a more stable extended duplex conformation in the presence of the core protein. Mutations in the dimer linkage sequence loop sequence that prevent RNA dimerization in vitro significantly reduced but did not completely ablate the ability of HCV RNA to replicate or produce infectious virus in transfected cells. PMID:20360391

  6. A p-quinodimethane-bridged porphyrin dimer.

    Science.gov (United States)

    Zeng, Wangdong; Ishida, Masatoshi; Lee, Sangsu; Sung, Young Mo; Zeng, Zebing; Ni, Yong; Chi, Chunyan; Kim, Dongho; Wu, Jishan

    2013-12-01

    A p-quinodimethane (p-QDM)-bridged porphyrin dimer 1 has been prepared for the first time. An unexpected Michael addition reaction took place when we attempted to synthesize compound 1 by reaction of the cross-conjugated keto-linked porphyrin dimers 8a and 8b with alkynyl/aryl Grignard reagents. Alternatively, compound 1 could be successfully prepared by intramolecular Friedel-Crafts alkylation of the diol-linked porphyrin dimer 14 with concomitant oxidation in air. Compound 1 shows intense one-photon absorption (OPA, λ(max)=955 nm, ε=45400 M(-1) cm(-1)) and a large two-photon absorption (TPA) cross-section (σ((2))(max)=2080 GM at 1800 nm) in the near-infrared (NIR) region due to its extended π-conjugation and quinoidal character. It also exhibits a short singlet excited-state lifetime of 25 ps. The cyclic voltammogram of 1 displays multiple redox waves with a small electrochemical energy gap of 0.86 eV. The ground-state geometry, electronic structure, and optical properties of 1 have been further studied by density functional theory (DFT) calculations and compared with those of the keto-linked dimer 8b. This research has revealed that incorporation of a p-QDM unit into the porphyrin framework had a significant impact on its optical and electronic properties, leading to a novel NIR OPA and TPA chromophore.

  7. Geometric Reid's recipe for dimer models

    NARCIS (Netherlands)

    Bocklandt, R.; Craw, A.; Quintero Vélez, A.

    2015-01-01

    Crepant resolutions of three-dimensional toric Gorenstein singularities are derived equivalent to noncommutative algebras arising from consistent dimer models. By choosing a special stability parameter and hence a distinguished crepant resolution Y, this derived equivalence generalises the Fourier-M

  8. The Diamagnetic Susceptibility of the Tubulin Dimer

    Directory of Open Access Journals (Sweden)

    Wim Bras

    2014-01-01

    Full Text Available An approximate value of the diamagnetic anisotropy of the tubulin dimer, Δχdimer, has been determined assuming axial symmetry and that only the α-helices and β-sheets contribute to the anisotropy. Two approaches have been utilized: (a using the value for the Δχα for an α-helical peptide bond given by Pauling (1979 and (b using the previously determined anisotropy of fibrinogen as a calibration standard. The Δχdimer≈4×10-27 JT−2 obtained from these measurements are similar to within 20%. Although Cotton-Mouton measurements alone cannot be used to estimate Δχ directly, the value we measured, CMdimer=1.41±0.03×10-8 T−2cm2mg−1, is consistent with the above estimate for Δχdimer. The method utilized for the determination of the tubulin dimer diamagnetic susceptibility is applicable to other proteins and macromolecular assemblies as well.

  9. A new lignan dimer from Mallotus philippensis.

    Science.gov (United States)

    Mai, Nguyen Thi; Cuong, Nguyen Xuan; Thao, Nguyen Phuong; Nam, Nguyen Hoai; Khoi, Nguyen Huu; Minh, Chau Van; Heyden, Yvan Vander; Thuan, Ngo Thi; Tuyen, Nguyen Van; Quetin-Leclercq, Joëlle; Kiem, Phan Van

    2010-03-01

    A new lignan dimer, bilariciresinol (1), was isolated from the leaves of Mallotus philippensis, along with platanoside (2), isovitexin (3), dihydromyricetin (4), bergenin (5), 4-O-galloylbergenin (6), and pachysandiol A (7). Their structures were elucidated by spectroscopic experiments including 1D and 2D NMR and FTICR-MS.

  10. Synthesis of novel 15-membered macrolide dimers

    Institute of Scientific and Technical Information of China (English)

    Shu Tao Ma; Rui Xin Ma; Rui Qing Xian; Bo Jiao

    2009-01-01

    A series of novel dimers of 15-memhered macrolides was synthesized and evaluated. The directs exhibited excellent activity against erythromycin-susceptible S. pneumonia, but did not show any improved activity against erythromycin-resistant S. pneumoniae encoded by erm gene.

  11. Amplitude enhancement by a gold dimer

    Science.gov (United States)

    Hong, Xin; Wang, Jingxin; Jin, Zheng

    2016-10-01

    The unique optical properties such as brightness, non-bleaching, good bio-compatibility make gold particles ideal label candidates for molecular probes. Due to the strongly enhanced field, aggregation of gold nanoparticles finds themselves plenty of applications in bio-imaging. But limited by its small cross-section associated with nanometer sized particle, it is a big challenge to employ it in a single molecular detection. The field enhancement results from the effect of plasmonic coupling between two closely attached gold nanoparticle under the right excitation condition. With the aim to apply the gold dimer probe to find the molecules in our recently established optical detection method, we compared of the amplitude enhancement by the dimer relative to a single particle. The amplitude distribution under a highly focused illumination objective was calculated, whose results suggest that at the optimized excitation condition, the local field can be enhanced 190 fold. In consequence, experimental detection was carried out. Gold dimers were linked together by the hybridization of two single chain DNAs. Dimer and single particle probes were mixed together in one detection. Overwhelming contrast between these two kinds of probes were clearly exhibited in the experimental detection image. This method can provide a way to a high specific detection in early diagnosis.

  12. D-二聚体的检测及临床应用%Detection and Application of D-dimer

    Institute of Scientific and Technical Information of China (English)

    张勇

    2011-01-01

    D-dimer is one of specific degradation products of cross-linked fibrin,D-dimer levels increase reflects the enhancement of secondary thrombolytic activity in vivo.In view of the formation principle of D-dimer has been widely used in clinical diagnosis and treatment,the clinical testing and application of D-dimer are emphatically reviewed.%D-二聚体是交联纤维蛋白的特异性降解产物之一,D-二聚体水平增高反映体内继发性纤溶活性增强.鉴于D-二聚体的形成原理已被广泛应用于临床诊断和治疗,现着重对D-二聚体的临床检测及应用作一综述.

  13. Structure of the nucleotide complex of PyrR, the pyr attenuation protein from Bacillus caldolyticus, suggests dual regulation by pyrimidine and purine nucleotides.

    Science.gov (United States)

    Chander, Preethi; Halbig, Kari M; Miller, Jamie K; Fields, Christopher J; Bonner, Heather K S; Grabner, Gail K; Switzer, Robert L; Smith, Janet L

    2005-03-01

    PyrR is a protein that regulates the expression of genes and operons of pyrimidine nucleotide biosynthesis (pyr genes) in many bacteria. PyrR acts by binding to specific sequences on pyr mRNA and causing transcriptional attenuation when intracellular levels of uridine nucleotides are elevated. PyrR from Bacillus subtilis has been purified and extensively studied. In this work, we describe the purification to homogeneity and characterization of recombinant PyrR from the thermophile Bacillus caldolyticus and the crystal structures of unliganded PyrR and a PyrR-nucleotide complex. The B. caldolyticus pyrR gene was previously shown to restore normal regulation of the B. subtilis pyr operon in a pyrR deletion mutant. Like B. subtilis PyrR, B. caldolyticus PyrR catalyzes the uracil phosphoribosyltransferase reaction but with maximal activity at 60 degrees C. Crystal structures of B. caldolyticus PyrR reveal a dimer similar to the B. subtilis PyrR dimer and, for the first time, binding sites for nucleotides. UMP and GMP, accompanied by Mg2+, bind specifically to PyrR active sites. Nucleotide binding to PyrR is similar to other phosphoribosyltransferases, but Mg2+ binding differs. GMP binding was unexpected. The protein bound specific sequences of pyr RNA 100 to 1,000 times more tightly than B. subtilis PyrR, depending on the RNA tested and the assay method; uridine nucleotides enhanced RNA binding, but guanosine nucleotides antagonized it. The new findings of specific GMP binding and its antagonism of RNA binding suggest cross-regulation of the pyr operon by purines.

  14. Universal bosonic tetramers of dimer-atom-atom structure

    OpenAIRE

    Deltuva, A.

    2012-01-01

    Unstable four-boson states having an approximate dimer-atom-atom structure are studied using momentum-space integral equations for the four-particle transition operators. For a given Efimov trimer the universal properties of the lowest associated tetramer are determined. The impact of this tetramer on the atom-trimer and dimer-dimer collisions is analyzed. The reliability of the three-body dimer-atom-atom model is studied.

  15. rac-(4R,17S,18R,26R-Ethyl 4′-methoxycarbonyl-5′′-(4-methoxyphenyl-1′-methyl-2,3′′-dioxo-2′′,3′′-dihydroindoline-3-spiro-2′-pyrrolidine-3′-spiro-2′′-thiazolo[3,2-a]pyrimidine-6′′-carboxylate

    Directory of Open Access Journals (Sweden)

    Xiao-Fang Li

    2009-02-01

    Full Text Available In the title compound, C30H30N4O7S, the two spiro junctions link a planar 2-oxindole ring [with a mean deviation from the plane of 0.0319 (3 Å, a pyrrolidine ring in an envelope conformation and a thiazolo[3,2-a]pyrimidine system. Two molecules are connected into a dimer by two N—H...O hydrogen bonds, forming an R22(8 graph-set motif. The title compound has four stereogenic centers and appears as a racemic mixture of one single diastereoisomer (RSRR/SRSS.

  16. Novel inhibitors of Mycobacterium tuberculosis growth based on modified pyrimidine nucleosides and their analogues

    Science.gov (United States)

    Shmalenyuk, E. R.; Kochetkov, S. N.; Alexandrova, L. A.

    2013-09-01

    The review summarizes data on the synthesis and antituberculosis activity of pyrimidine nucleoside derivatives and their analogues. Enzymes from M. tuberculosis as promising targets for prototypes of new-generation drugs are considered. Nucleosides as inhibitors of drug-resistant M. tuberculosis strains are characterized. The bibliography includes 101 references.

  17. Synthesis and anti-inflammatory activity of imidazo [1,2-a] pyrimidine derivatives

    Institute of Scientific and Technical Information of China (English)

    Jin Pei Zhou; Yi Wei Ding; Hui Bin Zhang; Lian Xu; Yue Dai

    2008-01-01

    A series of imidazo [1,2-a] pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.

  18. Ring transformations in reactions of pyrimidine and N-alkyl-pyridinium salts with nucleophiles

    NARCIS (Netherlands)

    Oostveen, E.A.

    1977-01-01

    Paper IOn treatment with liquid ammonia at -33°C, the quaternary pyrimidinium salts, i.e. 1-methylpyrimidinium methyl sulfate, 1,2-dimethylpyrimidinium iodide, 1,4,6-trimethyl-pyrimidinium iodide and 1,2,4,6-tetramethylpyrimidinium iodide demethylate yielding pyrimidine. 2-methyl-, 4,6-dimethyl- and

  19. Blockage of the pyrimidine biosynthetic pathway affects riboflavin production in Ashbya gossypii.

    Science.gov (United States)

    Silva, Rui; Aguiar, Tatiana Q; Domingues, Lucília

    2015-01-10

    The Ashbya gossypii riboflavin biosynthetic pathway and its connection with the purine pathway have been well studied. However, the outcome of genetic alterations in the pyrimidine pathway on riboflavin production by A. gossypii had not yet been assessed. Here, we report that the blockage of the de novo pyrimidine biosynthetic pathway in the recently generated A. gossypii Agura3 uridine/uracil auxotrophic strain led to improved riboflavin production on standard agar-solidified complex medium. When extra uridine/uracil was supplied, the production of riboflavin by this auxotroph was repressed. High concentrations of uracil hampered this (and the parent) strain growth, whereas excess uridine favored the A. gossypii Agura3 growth. Considering that the riboflavin and the pyrimidine pathways share the same precursors and that riboflavin overproduction may be triggered by nutritional stress, we suggest that overproduction of riboflavin by the A. gossypii Agura3 may occur as an outcome of a nutritional stress response and/or of an increased availability in precursors for riboflavin biosynthesis, due to their reduced consumption by the pyrimidine pathway.

  20. Quantifying the effects of halogen bonding by haloaromatic donors on the acceptor pyrimidine.

    Science.gov (United States)

    Ellington, Thomas L; Reves, Peyton L; Simms, Briana L; Wilson, Jamey L; Watkins, Davita L; Tschumper, Gregory S; Hammer, Nathan I

    2017-02-28

    The effects of intermolecular interactions by a series of haloaromatic halogen bond donors on the normal modes and chemical shifts of the acceptor pyrimidine are investigated by Raman and NMR spectroscopies and electronic structure computations. Halogen bond interactions with pyrimidine's nitrogen atoms shift normal modes to higher energy and shift 1H and 13C NMR peaks upfield in adjacent nuclei. This perturbation of vibrational normal modes is reminiscent of the effects of hydrogen bonded networks of water, methanol, or silver on pyrimidine. The unexpected observation of vibrational red shifts and downfield 13C NMR shifts in some complexes suggests that other intermolecular forces such as pi-interactions are competing with halogen bonding. Natural bond orbital analyses indicate a wide range of charge transfer from pyrimidine to different haloaromatic donors is possible and computed halogen bond binding energies can be larger than a typical hydrogen bond. These results emphasize the importance in strategic selection of substituents and electron withdrawing groups in developing supramolecular structures based on halogen bonding.

  1. beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities.

    NARCIS (Netherlands)

    Kuilenburg, A.B.P. van; Meinsma, R.; Beke, E.; Assmann, B.; Ribes, A.; Lorente, I.; Busch, R.; Mayatepek, E.; Abeling, N.G.G.M.; Cruchten, A.C. van; Stroomer, A.E.; Lenthe, H. van; Zoetekouw, L.; Kulik, W.; Hoffmann, G.F.; Voit, T.; Wevers, R.A.; Rutsch, F.; Gennip, A.H. van

    2004-01-01

    beta-Ureidopropionase deficiency is an inborn error of the pyrimidine degradation pathway, affecting the cleavage of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid. In this study, we report the elucidation of the genetic basis underlying a beta-ureidopropionase deficiency in four p

  2. Rapid and efficient synthesis of fused heterocyclic pyrimidines under ultrasonic irradiation.

    Science.gov (United States)

    Mosslemin, Mohammad Hossein; Nateghi, Mohammad Reza

    2010-01-01

    Some fused heterocyclic pyrimidines have been synthesized in high yields using ultrasound irradiation in a one-pot, three-component and efficient process by condensation reaction of barbituric acids, aldehydes and a series of enamines in water. Prominent among the advantages of this new method are operational simplicity, good yields in short reaction times and easy work-up procedures employed.

  3. Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity.

    Directory of Open Access Journals (Sweden)

    Marianne Lucas-Hourani

    Full Text Available Searching for stimulators of the innate antiviral response is an appealing approach to develop novel therapeutics against viral infections. Here, we established a cell-based reporter assay to identify compounds stimulating expression of interferon-inducible antiviral genes. DD264 was selected out of 41,353 compounds for both its immuno-stimulatory and antiviral properties. While searching for its mode of action, we identified DD264 as an inhibitor of pyrimidine biosynthesis pathway. This metabolic pathway was recently identified as a prime target of broad-spectrum antiviral molecules, but our data unraveled a yet unsuspected link with innate immunity. Indeed, we showed that DD264 or brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both enhanced the expression of antiviral genes in human cells. Furthermore, antiviral activity of DD264 or brequinar was found strictly dependent on cellular gene transcription, nuclear export machinery, and required IRF1 transcription factor. In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is not a direct consequence of pyrimidine deprivation on the virus machinery, but rather involves the induction of cellular immune response.

  4. An efficient and green preparation of 5-aminophosphonate substituted pyrimidine nucleosides under solvent-free conditions

    Institute of Scientific and Technical Information of China (English)

    Xin Ying Zhang; Ying Ying Qu; Xue Sen Fan

    2010-01-01

    An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed.By employing this method,5-aminophosphonate substituted pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-formyl-2'-deoxyuridine,aniline and dimethylphosphite.

  5. An Efficient and Facile Methodology for Bromination of Pyrimidine and Purine Nucleosides with Sodium Monobromoisocyanurate (SMBI

    Directory of Open Access Journals (Sweden)

    Roger Stromberg

    2013-10-01

    Full Text Available An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI. Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.

  6. Antimicrobial activity of new 4,6-disubstituted pyrimidine, pyrazoline, and pyran derivatives.

    Science.gov (United States)

    Ramiz, Mahmoud M M; El-Sayed, Wael A; El-Tantawy, Asmaa I; Abdel-Rahman, Adel A-H

    2010-05-01

    A number of new 2,6-didisubstituted pyrimidine, pyrazoline, and pyran derivatives were synthesized starting from their chalcone derivative. The synthesized compounds displayed different degrees of antimicrobial activity against Bscillus subtilis (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species (Actinomycetes).

  7. Tumour radiosensitization with the halogenated pyrimidines 5'-bromo-and 5'-iododeoxyuridine

    Energy Technology Data Exchange (ETDEWEB)

    Epstein, A.H.; Cook, J.A.; Goffman, T. (National Cancer Inst., Bethesda, MD (United States)); Glatstein, E. (Texas Univ., Dallas, TX (United States). Southwestern Medical Center)

    1993-02-01

    The authors review studies of the use of iododeoxyuridine (IdUrd) and bromodeoxyuridine as radiosensitizers and attempt to correlate the clinical outcome for patients treated with radiation and IdUrd with the extent of halogenated pyrimidine cellular uptake and incorporation. (U.K.).

  8. A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

    DEFF Research Database (Denmark)

    Andersen, Gorm; Bjornberg, Olof; Polakova, Silvia;

    2008-01-01

    Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyv...

  9. Ultraviolet Spectrum And Chemical Reactivity Of CIO Dimer

    Science.gov (United States)

    Demore, William B.; Tschuikow-Roux, E.

    1992-01-01

    Report describes experimental study of ultraviolet spectrum and chemical reactivity of dimer of chlorine monoxide (CIO). Objectives are to measure absorption cross sections of dimer at near-ultraviolet wavelengths; determine whether asymmetrical isomer (CIOCIO) exists at temperatures relevant to Antarctic stratosphere; and test for certain chemical reactions of dimer. Important in photochemistry of Antarctic stratosphere.

  10. A Nove Asymmetric ent—Kauranoid Dimer from Isodon enanderianus

    Institute of Scientific and Technical Information of China (English)

    纳智; 黎胜红; 等

    2002-01-01

    Further investigation on the aerial parts of Isodon enanderianus afforded a novel asymmetric ent-kauranoid dimer,enanderi-nanin J(1).The structure of the dimer was elucidated by means of spectroscopic methods (including 2D NMR tecniques ),Enanderinanin J was a dimer of xerophilusin A and probably formed by [4+2] cycloaddition.

  11. A Novel Asymmetric ent-Kauranoid Dimer from Isodon enanderianus

    Institute of Scientific and Technical Information of China (English)

    NA,Zhi(纳智); LI,Sheng-Hong(黎胜红); XIANG,Wei(项伟); ZHAO,Ai-Hua(赵爱华); LI,Chao-Ming(李朝明); SUN,Han-Dong(孙汉董)

    2002-01-01

    Further investigation on the aerial parts of Isodon enanderianus afforded a novel asymmetric ent-kauranoid dimer, enanuderinaninJ (1). The structure of the dimer was elucidated by means of spectroscopic methods (including 2D NMR techniques ). Enanderinanin J was a dimer of xerophilusin A and probably formed by [ 4 + 2] cycloaddition.

  12. Cyclic M2(RL)2 coordination complexes of 5-(3-[N-tert-Butyl-N-aminoxyl]phenyl)pyrimidine with paramagnetic transition metal dications.

    Science.gov (United States)

    Baskett, Martha; Lahti, Paul M; Paduan-Filho, Armando; Oliveira, Nei F

    2005-09-19

    5-(3-(N-tert-Butyl-N-aminoxyl)phenyl)pyrimidine (RL = 3NITPhPyrim) forms isostructural cyclic M2(RL)2 cyclic dimers with M(hfac)2 (M = Mn, Co, Cu; hfac = hexafluoroacetylacetonate). Mn2(hfac)4(RL)2 exhibits strong antiferromagnetic Mn-RL exchange, with weak ferromagnetic exchange (0.7 cm(-1)) between Mn-RL units that is consistent with a spin polarization exchange mechanism. The magnetic moment of Co2(hfac)4(RL)2 at higher temperatures is consistent with strongly antiferromagnetic exchange within the Co-NIT units and tends toward zero below 50 K at lower magnetic fields. Cu2(hfac)4(RL)2 shows more complex behavior, with no high-temperature plateau in chiT(T) up to 300 K but a monotonic decrease down to about 100 K. The Cu(II)-nitroxide bonds decrease by 0.2-0.3 A over the same temperature range, corresponding to a change of nitroxide coordination from axial to equatorial. This thermally reversible Jahn-Teller distortion leads to a thermally induced spin state conversion from a high-spin, paramagnetic state at higher temperature to a low-spin state at lower temperature. This spin state conversion is accompanied by a reversible solid-state thermochromic change between dull yellow-brown at room temperature and green at 77 K.

  13. Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP.

    Science.gov (United States)

    Rajagopal, Sathyanarayanan; Deb, Ishani; Poddar, Ranjana; Paul, Surojit

    2016-05-01

    The STriatal-Enriched tyrosine Phosphatase (STEP) is involved in the etiology of several age-associated neurologic disorders linked to oxidative stress and is also known to play a role in neuroprotection by modulating glutamatergic transmission. However, the possible effect of aging on STEP level and activity in the brain is still unclear. In this study, using young (1 month), adult (4 months), and aged (18 months) rats, we show that aging is associated with increase in dimerization and loss of activity of STEP. Increased dimerization of STEP is primarily observed in the cortex and hippocampus and is associated with depletion of both reduced and total glutathione levels, suggesting an increase in oxidative stress. Consistent with this interpretation, studies in cell culture models of glutathione depletion and oxidative stress also demonstrate formation of dimers and higher order oligomers of STEP that involve intermolecular disulfide bond formation between multiple cysteine residues. Conversely, administration of N-acetyl cysteine, a major antioxidant that enhances glutathione biosynthesis, attenuates STEP dimerization both in the cortex and hippocampus. The findings indicate that loss of this intrinsic protective response pathway with age-dependent increase in oxidative stress may be a contributing factor for the susceptibility of the brain to age-associated neurologic disorders.

  14. Thermochemical properties and contribution groups for ketene dimers and related structures from theoretical calculations.

    Science.gov (United States)

    Morales, Giovanni; Martínez, Ramiro

    2009-07-30

    This research's main goals were to analyze ketene dimers' relative stability and expand group additivity value (GAV) methodology for estimating the thermochemical properties of high-weight ketene polymers (up to tetramers). The CBS-Q multilevel procedure and statistical thermodynamics were used for calculating the thermochemical properties of 20 cyclic structures, such as diketenes, cyclobutane-1,3-diones, cyclobut-2-enones and pyran-4-ones, as well as 57 acyclic base compounds organized into five groups. According to theoretical heat of formation predictions, diketene was found to be thermodynamically favored over cyclobutane-1,3-dione and its enol-tautomeric form (3-hydroxycyclobut-2-enone). This result did not agree with old combustion experiments. 3-Hydroxycyclobut-2-enone was found to be the least stable dimer and its reported experimental detection in solution may have been due to solvent effects. Substituted diketenes had lower stability than substituted cyclobutane-1,3-diones with an increased number of methyl substituents, suggesting that cyclobutane-1,3-dione type dimers are the major products because of thermodynamic control of alkylketene dimerization. Missing GAVs for the ketene dimers and related structures were calculated through linear regression on the 57 acyclic base compounds. Corrections for non next neighbor interactions (such as gauche, eclipses, and internal hydrogen bond) were needed for obtaining a highly accurate and precise regression model. To the best of our knowledge, the hydrogen bond correction for GAV methodology is the first reported in the literature; this correction was correlated to MP2/6-31Gdagger and HF/6-31Gdagger derived geometries to facilitate its application. GAVs assessed by the linear regression model were able to reproduce acyclic compounds' theoretical thermochemical properties and experimental heat of formation for acetylacetone. Ring formation and substituent position corrections were calculated by consecutively

  15. The enzymology of cytosolic pyrimidine 5'-nucleotidases: functional analysis and physiopathological implications.

    Science.gov (United States)

    Magni, Giulio; Amici, Adolfo; Orsomando, Giuseppe

    2013-01-01

    In mammals, cellular 5'-nucleotidase (5'-NT) activity (EC 3.1.3.5) encompasses a number of genetically and structurally distinct enzyme forms, either membrane-bound or soluble, mainly cytosolic, that are characterized by broad specificity towards nucleoside 5'-monophosphate substrates differing in base (purine/pyrimidine) and/or sugar (oxy/deoxy-ribose) moieties. In particular, among the cytosolic 5'-NTs active towards pyrimidine nucleotides are cN-III and cdN, ubiquitously distributed in mammalian tissues and treated as a single entity in the early days. cN-III was first linked to a genetic defect , hereditary pyrimidine nucleotidase deficiency, associated to a nonspherocyt ic hemolytic anemia disorder of still unclear mechanism but metabolically characterized by abnormally high levels of pyrimidine compounds and ribonucleoproteins in erythrocytes, as evidenced by occurrence of basophilic stippling on blood smearings. Since the first review on pyrimidine-specific nucleotidases (Amici, A.; Magni, G., Arch. Biochem. Biophys., 2002, 397(2), 184- 190), excellent overviews on the topic appeared in the literature. In the present contribution, the major findings on these two enzymatic proteins, cN-III and cdN, will be described with particular emphasis on the relationships between their structure and function, as well as on their roles in normal and pathological conditions. The catalytic mechanism of both specific hydrolytic and phosphotransferase activities, possessed by both enzymes, will be discussed also in the light of recent solution of both cN-III and cdN three-dimensional structures. This review also focuses on possible therapeutic approaches involving cellular 5'-NTs in detoxifying common antiviral and antineoplastic drugs.

  16. Medicinal attributes of pyrazolo[1,5-a]pyrimidine based scaffold derivatives targeting kinases as anticancer agents

    Directory of Open Access Journals (Sweden)

    Nasser S.M. Ismail

    2016-12-01

    Full Text Available Pyrazolo pyrimidines are fused heterocyclic ring systems which known as bioisosteres of adenine, that are necessary for every aspect of cell life. Pyrazolo[1,5-a]pyrimidines derivatives have been explored for their inhibitory activity towards a variety of protein kinase enzymes and their function as anticancer agents. This review to the best of our knowledge is the first assemblage on synthesis and medicinal aspects including structure activity relationships of pyrazolo[1,5-a]pyrimidines reported to date.

  17. Biochemical, mutational and in silico structural evidence for a functional dimeric form of the ornithine decarboxylase from Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Preeti

    Full Text Available BACKGROUND: Entamoeba histolytica is responsible for causing amoebiasis. Polyamine biosynthesis pathway enzymes are potential drug targets in parasitic protozoan diseases. The first and rate-limiting step of this pathway is catalyzed by ornithine decarboxylase (ODC. ODC enzyme functions as an obligate dimer. However, partially purified ODC from E. histolytica (EhODC is reported to exist in a pentameric state. METHODOLOGY AND RESULTS: In present study, the oligomeric state of EhODC was re-investigated. The enzyme was over-expressed in Escherichia coli and purified. Pure protein was used for determination of secondary structure content using circular dichroism spectroscopy. The percentages of α-helix, β-sheets and random coils in EhODC were estimated to be 39%, 25% and 36% respectively. Size-exclusion chromatography and mass spectrophotometry analysis revealed that EhODC enzyme exists in dimeric form. Further, computational model of EhODC dimer was generated. The homodimer contains two separate active sites at the dimer interface with Lys57 and Cys334 residues of opposite monomers contributing to each active site. Molecular dynamic simulations were performed and the dimeric structure was found to be very stable with RMSD value ∼0.327 nm. To gain insight into the functional role, the interface residues critical for dimerization and active site formation were identified and mutated. Mutation of Lys57Ala or Cys334Ala completely abolished enzyme activity. Interestingly, partial restoration of the enzyme activity was observed when inactive Lys57Ala and Cys334Ala mutants were mixed confirming that the dimer is the active form. Furthermore, Gly361Tyr and Lys157Ala mutations at the dimer interface were found to abolish the enzyme activity and destabilize the dimer. CONCLUSION: To our knowledge, this is the first report which demonstrates that EhODC is functional in the dimeric form. These findings and availability of 3D structure model of EhODC dimer

  18. Computational Study of Monosubstituted Azo(tetrazolepentazolium)-Based Ionic Dimers.

    Science.gov (United States)

    Pimienta, Ian S O

    2015-06-04

    The structures of monosubstituted azo(tetrazolepentazolium) cations (N11CHR(+)), oxygen-rich anions such as N(NO2)2(-), NO3(-), and ClO4(-), and the corresponding ion pairs are investigated using ab initio quantum chemistry calculations. The substituents (R) used are H, F, CH3, CN, NH2, OH, OCH3, N3, NF2, and C2H3. The stability of the protonated cation is explored by examining the decomposition pathway of the protonated cation (N11CH2(+)) to yield molecular N2 fragments. The heats of formation of these cations, which are based on isodesmic (bond type conserving) reactions, are dependent on the nature of the substituents. Ionic dimer structures are obtained, but side reactions including proton transfer, binding, and hydrogen bonding are observed in the gas phase. Implicit solvation studies are performed to determine the solution properties of the ion pairs.

  19. Large D-Dimer Fluctuation in Normal Pregnancy

    DEFF Research Database (Denmark)

    Hedengran, Katrine K; Andersen, Malene R; Stender, Steen

    2016-01-01

    pregnancies were recruited. D-dimer was repeatedly measured during pregnancy, at active labor, and on the first and second postpartum days. Percentiles for each gestational week were calculated. Each individual D-dimer was normalized by transformation into percentiles for the relevant gestational age......Introduction. D-dimer levels increase throughout pregnancy, hampering the usefulness of the conventional threshold for dismissing thromboembolism. This study investigates the biological fluctuation of D-dimer in normal pregnancy. Methods. A total of 801 healthy women with expected normal...... normal pregnancy, repeated D-dimer measurements are of no clinical use in the evaluation of thromboembolic events during pregnancy....

  20. Plasmonic rod dimers as elementary planar chiral meta-atoms

    CERN Document Server

    Zhukovsky, Sergei V; Chigrin, Dmitry N

    2011-01-01

    Electromagnetic response of metallic rod dimers is theoretically calculated for arbitrary planar arrangement of rods in the dimer. It is shown that dimers without an in-plane symmetry axis exhibit elliptical dichroism and act as "atoms" in planar chiral metamaterials. Due to a very simple geometry of the rod dimer, such planar metamaterials are much easier in fabrication than conventional split-ring or gammadion-type structures, and lend themselves to a simple analytical treatment based on coupled dipole model. Dependencies of metamaterial's directional asymmetry on the dimer's geometry are established analytically and confirmed in numerical simulations.

  1. Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds.

    Science.gov (United States)

    Eng, Elizabeth T; Ye, JingJing; Williams, Dudley; Phung, Sheryl; Moore, Roger E; Young, Mary K; Gruntmanis, Ugis; Braunstein, Glenn; Chen, Shiuan

    2003-12-01

    In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a K(i) value of 6 micro M. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.

  2. Calcium-dependent Dimerization of Human Soluble Calcium Activated Nucleotidase: Characterization of the Dimer Interface

    Energy Technology Data Exchange (ETDEWEB)

    Yang,M.; Horii, K.; Herr, A.; Kirley, T.

    2006-01-01

    Mammals express a protein homologous to soluble nucleotidases used by blood-sucking insects to inhibit host blood clotting. These vertebrate nucleotidases may play a role in protein glycosylation. The activity of this enzyme family is strictly dependent on calcium, which induces a conformational change in the secreted, soluble human nucleotidase. The crystal structure of this human enzyme was recently solved; however, the mechanism of calcium activation and the basis for the calcium-induced changes remain unclear. In this study, using analytical ultracentrifugation and chemical cross-linking, we show that calcium or strontium induce noncovalent dimerization of the soluble human enzyme. The location and nature of the dimer interface was elucidated using a combination of site-directed mutagenesis and chemical cross-linking, coupled with crystallographic analyses. Replacement of Ile{sup 170}, Ser{sup 172}, and Ser{sup 226} with cysteine residues resulted in calcium-dependent, sulfhydryl-specific intermolecular cross-linking, which was not observed after cysteine introduction at other surface locations. Analysis of a super-active mutant, E130Y, revealed that this mutant dimerized more readily than the wild-type enzyme. The crystal structure of the E130Y mutant revealed that the mutated residue is found in the dimer interface. In addition, expression of the full-length nucleotidase revealed that this membrane-bound form can also dimerize and that these dimers are stabilized by spontaneous oxidative cross-linking of Cys{sup 30}, located between the single transmembrane helix and the start of the soluble sequence. Thus, calcium-mediated dimerization may also represent a mechanism for regulation of the activity of this nucleotidase in the physiological setting of the endoplasmic reticulum or Golgi.

  3. Revisiting the Optical PT-Symmetric Dimer

    Directory of Open Access Journals (Sweden)

    José Delfino Huerta Morales

    2016-08-01

    Full Text Available Optics has proved a fertile ground for the experimental simulation of quantum mechanics. Most recently, optical realizations of PT -symmetric quantum mechanics have been shown, both theoretically and experimentally, opening the door to international efforts aiming at the design of practical optical devices exploiting this symmetry. Here, we focus on the optical PT -symmetric dimer, a two-waveguide coupler where the materials show symmetric effective gain and loss, and provide a review of the linear and nonlinear optical realizations from a symmetry-based point of view. We go beyond a simple review of the literature and show that the dimer is just the smallest of a class of planar N-waveguide couplers that are the optical realization of the Lorentz group in 2 + 1 dimensions. Furthermore, we provide a formulation to describe light propagation through waveguide couplers described by non-Hermitian mode coupling matrices based on a non-Hermitian generalization of the Ehrenfest theorem.

  4. Revisiting the optical $PT$-symmetric dimer

    CERN Document Server

    Morales, J D Huerta; López-Aguayo, S; Rodríguez-Lara, B M

    2016-01-01

    Optics has proved a fertile ground for the experimental simulation of quantum mechanics. Most recently, optical realizations of $\\mathcal{PT}$-symmetric quantum mechanics have been shown, both theoretically and experimentally, opening the door to international efforts aiming at the design of practical optical devices exploiting this symmetry. Here, we focus on the optical $\\mathcal{PT}$-symmetric dimer, a two-waveguide coupler were the materials show symmetric effective gain and loss, and provide a review of the linear and nonlinear optical realizations from a symmetry based point of view. We go beyond a simple review of the literature and show that the dimer is just the smallest of a class of planar $N$-waveguide couplers that are the optical realization of Lorentz group in 2+1 dimensions. Furthermore, we provide a formulation to describe light propagation through waveguide couplers described by non-Hermitian mode coupling matrices based on a non-Hermitian generalization of Ehrenfest theorem.

  5. Entanglement and decoherence in a quantum dimer

    Institute of Scientific and Technical Information of China (English)

    Hou Xi-Wen; Hui Zi; Ding Rui-Min; Chen Xiao-Yang; Gao Yu

    2006-01-01

    The dynamical properties of quantum entanglement in an integrable quantum dimer are studied in terms of the reduced-density linear entropy with various coupling parameters and total boson numbers. The characteristic time of decoherence process in the early-time evolution of the linear entropy is obtained, indicating that the characteristic time and the corresponding entropy exhibit a maximum near the position of the corresponding classical separatrix energy.

  6. Path integrals for dimerized quantum spin systems

    Energy Technology Data Exchange (ETDEWEB)

    Foussats, Adriana, E-mail: afoussats@gmail.co [Facultad de Ciencias Exactas, Ingenieria y Agrimensura and Instituto de Fisica Rosario (UNR-CONICET), Av. Pellegrini 250, 2000 Rosario (Argentina); Greco, Andres [Facultad de Ciencias Exactas, Ingenieria y Agrimensura and Instituto de Fisica Rosario (UNR-CONICET), Av. Pellegrini 250, 2000 Rosario (Argentina); Muramatsu, Alejandro [Institut fuer Theoretische Physik III, Universitaet Stuttgart, Pfaffenwaldring 57, D-70550 Stuttgart (Germany)

    2011-01-11

    Dimerized quantum spin systems may appear under several circumstances, e.g. by a modulation of the antiferromagnetic exchange coupling in space, or in frustrated quantum antiferromagnets. In general, such systems display a quantum phase transition to a Neel state as a function of a suitable coupling constant. We present here two path-integral formulations appropriate for spin S=1/2 dimerized systems. The first one deals with a description of the dimers degrees of freedom in an SO(4) manifold, while the second one provides a path-integral for the bond-operators introduced by Sachdev and Bhatt. The path-integral quantization is performed using the Faddeev-Jackiw symplectic formalism for constrained systems, such that the measures and constraints that result from the algebra of the operators is provided in both cases. As an example we consider a spin-Peierls chain, and show how to arrive at the corresponding field-theory, starting with both an SO(4) formulation and bond-operators.

  7. Dimerization and heme binding are conserved in amphibian and starfish homologues of the microRNA processing protein DGCR8.

    Directory of Open Access Journals (Sweden)

    Rachel Senturia

    Full Text Available Human DiGeorge Critical Region 8 (DGCR8 is an essential microRNA (miRNA processing factor that is activated via direct interaction with Fe(III heme. In order for DGCR8 to bind heme, it must dimerize using a dimerization domain embedded within its heme-binding domain (HBD. We previously reported a crystal structure of the dimerization domain from human DGCR8, which demonstrated how dimerization results in the formation of a surface important for association with heme. Here, in an attempt to crystallize the HBD, we search for DGCR8 homologues and show that DGCR8 from Patiria miniata (bat star also binds heme. The extinction coefficients (ε of DGCR8-heme complexes are determined; these values are useful for biochemical analyses and allow us to estimate the heme occupancy of DGCR8 proteins. Additionally, we present the crystal structure of the Xenopus laevis dimerization domain. The structure is very similar to that of human DGCR8. Our results indicate that dimerization and heme binding are evolutionarily conserved properties of DGCR8 homologues not only in vertebrates, but also in at least some invertebrates.

  8. Chiroptical properties, binding affinity, and photostability of a conjugated zinc porphyrin dimer complexed with left-handed Z-DNA and right-handed B-DNA.

    Science.gov (United States)

    Choi, Jung Kyu; Reed, Aisha; Balaz, Milan

    2014-01-14

    We have studied the UV-vis absorption and chiroptical properties, binding affinity and photostability of a conjugated positively charged butadiyne-linked Zn(ii) porphyrin dimer bound to DNA sequence poly(dG-dC)2. Right-handed B-DNA, spermine-induced Z-DNA and Co(iii)-induced Z-DNA have been explored. Resonance light scattering (RLS) spectra showed formation of porphyrin aggregates in the presence of all DNA forms with the largest aggregates formed with B-DNA. The porphyrin dimer gave rise to induced bisignate circular dichroism (CD) signals in the presence of the left-handed Z-DNA conformations. On the other hand, the dimer stayed nearly chiroptically silent when complexed with the B-form of poly(dG-dC)2. Our results indicated that the conjugated Zn(ii) porphyrin dimer can be used as a sensor for the chiroptical detection of Z-DNA in the visible (400-500 nm) and near-infrared region of the electromagnetic spectrum (700-800 nm). The helicity of DNA had little effect on the dimer binding affinities. The photostability of the porphyrin dimer complexed with any form of DNA was higher than that of the free molecule. The porphyrin dimer bound to Z-DNA exhibited slower photobleaching than the B-DNA dimer complex.

  9. Powerful methods to establish chromosomal markers in Lactococcus lactis: an analysis of pyrimidine salvage pathway mutants obtained by positive selections

    DEFF Research Database (Denmark)

    Martinussen, Jan; Hammer, Karin

    1995-01-01

    phosphoribosyltransferase (upp), uridindcytidine kinase (udk), pyrimidine nucleoside phosphorylase (pdp), cytidine/deoxycytidine deaminase (dd), thymidine kinase (tdk) and purine nucleoride phosphorylase (pup). Based on an analysis of the mutants obtained, the pathways by which L. lactis metabolizes uracil...

  10. Probing the roles of the two different dimers mediated by the receiver domain of the response regulator PhoB.

    Science.gov (United States)

    Mack, Timothy R; Gao, Rong; Stock, Ann M

    2009-06-05

    Structural analysis of the Escherichia coli response regulator transcription factor PhoB indicates that the protein dimerizes in two different orientations that are both mediated by the receiver domain. The two dimers exhibit 2-fold rotational symmetry: one involves the alpha 4-beta 5-alpha 5 surface and the other involves the alpha1/alpha 5 surface. The alpha 4-beta 5-alpha 5 dimer is observed when the protein is crystallized in the presence of the phosphoryl analog BeF(3)(-), while the alpha1/alpha 5 dimer is observed in its absence. From these studies, a model of the inactive and active states of PhoB has been proposed that involves the formation of two distinct dimers. In order to gain further insight into the roles of these dimers, we have engineered a series of mutations in PhoB intended to perturb each of them selectively. Our results indicate that perturbation of the alpha 4-beta 5-alpha 5 surface disrupts phosphorylation-dependent dimerization and DNA binding as well as PhoB-mediated transcriptional activation of phoA, while perturbations to the alpha1/alpha 5 surface do not. Furthermore, experiments with a GCN4 leucine zipper/PhoB chimera protein indicate that PhoB is activated through an intermolecular mechanism. Together, these results support a model of activation of PhoB in which phosphorylation promotes dimerization via the alpha 4-beta 5-alpha 5 face, which enhances DNA binding and thus the ability of PhoB to regulate transcription.

  11. MspA nanopores from subunit dimers.

    Directory of Open Access Journals (Sweden)

    Mikhail Pavlenok

    Full Text Available Mycobacterium smegmatis porin A (MspA forms an octameric channel and represents the founding member of a new family of pore proteins. Control of subunit stoichiometry is important to tailor MspA for nanotechnological applications. In this study, two MspA monomers were connected by linkers ranging from 17 to 62 amino acids in length. The oligomeric pore proteins were purified from M. smegmatis and were shown to form functional channels in lipid bilayer experiments. These results indicated that the peptide linkers did not prohibit correct folding and localization of MspA. However, expression levels were reduced by 10-fold compared to wild-type MspA. MspA is ideal for nanopore sequencing due to its unique pore geometry and its robustness. To assess the usefulness of MspA made from dimeric subunits for DNA sequencing, we linked two M1-MspA monomers, whose constriction zones were modified to enable DNA translocation. Lipid bilayer experiments demonstrated that this construct also formed functional channels. Voltage gating of MspA pores made from M1 monomers and M1-M1 dimers was identical indicating similar structural and dynamic channel properties. Glucose uptake in M. smegmatis cells lacking porins was restored by expressing the dimeric mspA M1 gene indicating correct folding and localization of M1-M1 pores in their native membrane. Single-stranded DNA hairpins produced identical ionic current blockades in pores made from monomers and subunit dimers demonstrating that M1-M1 pores are suitable for DNA sequencing. This study provides the proof of principle that production of single-chain MspA pores in M. smegmatis is feasible and paves the way for generating MspA pores with altered stoichiometries. Subunit dimers enable better control of the chemical and physical properties of the constriction zone of MspA. This approach will be valuable both in understanding transport across the outer membrane in mycobacteria and in tailoring MspA for nanopore

  12. Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

    Directory of Open Access Journals (Sweden)

    Hafez Hend N.

    2016-09-01

    Full Text Available 6ʹ-(4-Chlorophenyl-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH-one (1 was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3ʹ-(4-acetylphenyl-6ʹ- (4-chlorophenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH-one (3. Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl-1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z-3-substituted-arylprop-2-enoyl] phenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-ylphenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a-e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4-yl-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 μmol mL-1 compared to ketoconazole (MIC 2-3 μmol mL-1 .

  13. Polarons in endohedral Li+@C60- dimers and in 1D and 2D crystals

    Science.gov (United States)

    Kawazoe, Yoshiyuki; Belosludov, Vladimir R.; Zhdanov, Ravil K.; Belosludov, Rodion V.

    2017-10-01

    The electron charge distribution and polaron formation on the carbon sites of dimer clusters Li+@C60- and of 1D or 2D Li+@C60- periodic systems are studied with the use of the generalized Su-Schrieffer-Heeger model with respect to the intermolecular and intramolecular degrees of freedom. The charge distributions over the molecular surface and Jahn-Teller bond distortions of carbon atoms are calculated using the self-consistent iterative methods. Polarons formed in periodic 1D and 2D systems (chains and planar layers) as well as in dimer cluster system are examined. In the periodic systems polaron formation may be described by the cooperative Jahn-Teller effect. Orientation of the polarons on the molecule surface depends on the doping of the system, moreover, electron doping changes the energy levels in the system.

  14. Electronic transition dipole moment and radiative lifetime calculations of sodium dimer ion-pair states.

    Science.gov (United States)

    Sanli, Aydin; Beser, Bediha; Edwardson, John R; Magnier, Sylvie; Ahmed, Ergin H; Marjatta Lyyra, A

    2015-09-14

    We report here ab initio calculated electronic transition dipole moments for the sodium dimer ion pair states of (1)Σg (+) symmetry. They vary strongly as a function of internuclear distance because of the effect of the Na(+) + Na(-) ion pair potential, which also causes the formation of additional wells and shoulders in the molecular potential energy curves. We also present a computational study of the transition dipole moment matrix elements and lifetimes for these ion-pair states.

  15. Experimental and theoretical studies on the coordination chemistry of the N1-hexyl substituted pyrimidines (uracil, 5-fluorouracil and cytosine).

    Science.gov (United States)

    Barceló-Oliver, Miquel; Baquero, Beatriz Adriana; Bauzá, Antonio; García-Raso, Angel; Vich, Roberto; Mata, Ignasi; Molins, Elies; Terrón, Angel; Frontera, Antonio

    2013-06-01

    N(1)-Hexyl substituted pyrimidines were shown to present solubility properties closer to the real bases than the commonly used methyl and ethyl derivatives, yielding bi-layered structures in the solid state. The study of their coordination capabilities, mainly with Ag(I) and Hg(II), is presented in order to prove their reactivity. A series of coordination complexes, namely, [Hg(N(1)-hexyl-5-fluorouracilate)2]4·6H2O (1), (Ag(+))·[Ag(N(1)-hexyl-5-fluorouracilate)2](-) (2), [Ag(NO3)(N(1)-hexyluracil-κO(4))4] (3), [ZnBr2(N(1)-hexylcytosine)2] (4), [CdBr2(N(1)-hexylcytosine)2] (5), [HgBr2(N(1)-hexylcytosine)2] (6) and [CoBr2(N(1)-hexylcytosine)2] (7), have been synthesized in good yields and X-ray characterized. The presence of the hexyl chains and the fluorine atoms causes the formation of interesting 3D architectures in the solid state. Their structures have been further characterized by infrared spectra (IR) and elemental analyses. In addition, DFT-D3 calculations are used to study interesting noncovalent interactions observed in the solid state, like fluorine-fluorine, fluorine-π and hydrophobic interactions.

  16. Targeting DNA with "light-up" pyrimidine triple-helical forming oligonucleotides conjugated to stabilizing fluorophores (LU-TFOs).

    Science.gov (United States)

    Renard, Brice-Loïc; Lartia, Rémy; Asseline, Ulysse

    2008-12-07

    The synthesis of triple-helix-forming oligonucleotides (TFOs) linked to a series of cyanine monomethines has been performed. Eight cyanines including one thiocyanine, four thiazole orange analogues, and three quinocyanines were attached to the 5'-end of 10-mer pyrimidine TFOs. The binding properties of these modified TFOs with their double-stranded DNA target were studied by absorption and steady-state fluorescence spectroscopy. The stability of the triplex structures depended on the cyanine structure and the linker size used to connect both entities. The most efficient cyanines able to stabilize the triplex structures, when attached at the 5'-end of the TFO, have been incorporated at both ends and provided triplex structures with increased stability. Fluorescence studies have shown that for the TFOs involving one cyanine, an important intensity increase (up to 37-fold) in the fluorescent signal was observed upon their hybridization with the double-stranded target, proving hybridization. The conjugates involving thiazole orange attached by the benzothiazole ring provided the most balanced properties in terms of triplex stabilization, fluorescence intensity and fluorescence enhancement upon hybridization with the double-stranded target. In order to test the influence of different parameters such as the TFO sequence and length, thiazole orange was used to label 17-mer TFOs. Hybridizations of these TFOs with different duplexes, designed to study the influence of mismatches at both internal and terminal positions on the triplex structures, confirmed the possibility of triplex formation without loss of specificity together with a strong fluorescence enhancement (up to 13-fold).

  17. Structure of a Light-Activated LOV Protein Dimer That Regulates Transcription

    Energy Technology Data Exchange (ETDEWEB)

    Vaidya, Anand T.; Chen, Chen-Hui; Dunlap, Jay C.; Loros, Jennifer J.; Crane, Brian R. (Dartmouth-MED); (Cornell)

    2012-10-25

    Light, oxygen, or voltage (LOV) protein domains are present in many signaling proteins in bacteria, archaea, protists, plants, and fungi. The LOV protein VIVID (VVD) of the filamentous fungus Neurospora crassa enables the organism to adapt to constant or increasing amounts of light and facilitates proper entrainment of circadian rhythms. Here, we determined the crystal structure of the fully light-adapted VVD dimer and reveal the mechanism by which light-driven conformational change alters the oligomeric state of the protein. Light-induced formation of a cysteinyl-flavin adduct generated a new hydrogen bond network that released the amino (N) terminus from the protein core and restructured an acceptor pocket for binding of the N terminus on the opposite subunit of the dimer. Substitution of residues critical for the switch between the monomeric and the dimeric states of the protein had profound effects on light adaptation in Neurospora. The mechanism of dimerization of VVD provides molecular details that explain how members of a large family of photoreceptors convert light responses to alterations in protein-protein interactions.

  18. Mapping of the dimer interface of the Escherichia coli mannitol permease by cysteine cross-linking.

    Science.gov (United States)

    van Montfort, Bart A; Schuurman-Wolters, Gea K; Wind, Joyce; Broos, Jaap; Robillard, George T; Poolman, Bert

    2002-04-26

    A cysteine cross-linking approach was used to identify residues at the dimer interface of the Escherichia coli mannitol permease. This transport protein comprises two cytoplasmic domains and one membrane-embedded C domain per monomer, of which the latter provides the dimer contacts. A series of single-cysteine His-tagged C domains present in the native membrane were subjected to Cu(II)-(1,10-phenanthroline)(3)-catalyzed disulfide formation or cysteine cross-linking with dimaleimides of different length. The engineered cysteines were at the borders of the predicted membrane-spanning alpha-helices. Two residues were found to be located in close proximity of each other and capable of forming a disulfide, while four other locations formed cross-links with the longer dimaleimides. Solubilization of the membranes did only influence the cross-linking behavior at one position (Cys(73)). Mannitol binding only effected the cross-linking of a cysteine at the border of the third transmembrane helix (Cys(134)), indicating that substrate binding does not lead to large rearrangements in the helix packing or to dissociation of the dimer. Upon mannitol binding, the Cys(134) becomes more exposed but the residue is no longer capable of forming a stable disulfide in the dimeric IIC domain. In combination with the recently obtained projection structure of the IIC domain in two-dimensional crystals, a first proposal is made for alpha-helix packing in the mannitol permease.

  19. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    Directory of Open Access Journals (Sweden)

    Masao Terasawa

    Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

  20. Biopolymer from microbial assisted in situ hydrolysis of triglycerides and dimerization of fatty acids.

    Science.gov (United States)

    Kavitha, V; Radhakrishnan, N; Madhavacharyulu, E; Sailakshmi, G; Sekaran, G; Reddy, B S R; Rajkumar, G Suseela; Gnanamani, Arumugam

    2010-01-01

    The present study demonstrates biopolymer production by in situ bio-based dimerization of fatty acids by microorganism isolated from marine sediments. Microbial isolate grown in Zobell medium in the presence of triglycerides for the period of 24-240 h at 37 degrees C, hydrolyze the applied triglycerides and sequentially dimerized the hydrolyzed products and subsequently polymerized and transformed to a biopolymer having appreciable adhesive properties. Physical (nature, odour, stickyness and tensile strength), chemical (instrumentation) and biochemical (cell free broth) methods of analyses carried out provided the hypotheses involved in the formation of the product as well as the nature of the product formed. Results revealed, lipolytic enzymes released during initial period of growth and the biosurfactant production during later period, respectively, hydrolyze the applied triglycerides and initiate the dimerization and further accelerated when the incubation period extended. The existence and the non-existence of in situ hydrolysis of various triglycerides followed by dimerization and polymerization and the mechanism of transformation of triglycerides to biopolymer are discussed in detail.

  1. Fluorescence Microspectroscopy for Testing the Dimerization Hypothesis of BACE1 Protein in Cultured HEK293 Cells

    Science.gov (United States)

    Gardeen, Spencer; Johnson, Joseph L.; Heikal, Ahmed A.

    2016-06-01

    Alzheimer's Disease (AD) is a neurodegenerative disorder that results from the formation of beta-amyloid plaques in the brain that trigger the known symptoms of memory loss in AD patients. The beta-amyloid plaques are formed by the proteolytic cleavage of the amyloid precursor protein (APP) by the proteases BACE1 and gamma-secretase. These enzyme-facilitated cleavages lead to the production of beta-amyloid fragments that aggregate to form plaques, which ultimately lead to neuronal cell death. Recent detergent protein extraction studies suggest that BACE1 protein forms a dimer that has significantly higher catalytic activity than its monomeric counterpart. In this contribution, we examine the dimerization hypothesis of BACE1 in cultured HEK293 cells using complementary fluorescence spectroscopy and microscopy methods. Cells were transfected with a BACE1-EGFP fusion protein construct and imaged using confocal, and differential interference contrast to monitor the localization and distribution of intracellular BACE1. Complementary fluorescence lifetime and anisotropy measurements enabled us to examine the conformational and environmental changes of BACE1 as a function of substrate binding. Using fluorescence correlation spectroscopy, we also quantified the diffusion coefficient of BACE1-EGFP on the plasma membrane as a means to test the dimerization hypothesis as a fucntion of substrate-analog inhibitition. Our results represent an important first towards examining the substrate-mediated dimerization hypothesis of BACE1 in live cells.

  2. Disturbing the dimers: Electron and hole doping in the intermetallic insulator FeGa3

    Science.gov (United States)

    Botana, Antia S.; Quan, Yundi; Pickett, Warren E.

    2015-10-01

    Insulating FeGa3 poses peculiar puzzles beyond the occurrence of an electronic gap in an intermetallic compound. This Fe-based material has a very distinctive structural characteristic with the Fe atoms occurring in dimers. The insulating gap can be described comparably well in either the weakly correlated limit or the strongly correlated limit within density functional theory viewpoints, where the latter corresponds to singlet formation on the Fe2 dimers. Though most of the calculated occupied Wannier functions are an admixture of Fe 3 d and Ga 4 s or 4 p states, there is a single bonding-type Wannier function per spin centered on each Fe2 dimer. Density functional theory methods have been applied to follow the evolution of the magnetic properties and electronic spectrum with doping, where unusual behavior is observed experimentally. Both electron and hole doping are considered, by Ge and Zn on the Ga site, and by Co and Mn on the Fe site, the latter introducing direct disturbance of the Fe2 dimer. Results from weakly and strongly correlated pictures are compared. Regardless of the method, magnetism including itinerant phases appears readily with doping. The correlated picture suggests that in the low doping limit Mn (for Fe) produces an in-gap hole state, while Co (for Fe) introduces a localized electronic gap state.

  3. Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant

    Science.gov (United States)

    Merlino, Antonello; Avella, Giovanna; Di Gaetano, Sonia; Arciello, Angela; Piccoli, Renata; Mazzarella, Lelio; Sica, Filomena

    2009-01-01

    A specialized class of RNases shows a high cytotoxicity toward tumor cell lines, which is critically dependent on their ability to reach the cytosol and to evade the action of the ribonuclease inhibitor (RI). The cytotoxicity and antitumor activity of bovine seminal ribonuclease (BSRNase), which exists in the native state as an equilibrium mixture of a swapped and an unswapped dimer, are peculiar properties of the swapped form. A dimeric variant (HHP2-RNase) of human pancreatic RNase, in which the enzyme has been engineered to reproduce the sequence of BSRNase helix-II (Gln28→Leu, Arg31→Cys, Arg32→Cys, and Asn34→Lys) and to eliminate a negative charge on the surface (Glu111→Gly), is also extremely cytotoxic. Surprisingly, this activity is associated also to the unswapped form of the protein. The crystal structure reveals that on this molecule the hinge regions, which are highly disordered in the unswapped form of BSRNase, adopt a very well-defined conformation in both subunits. The results suggest that the two hinge peptides and the two Leu28 side chains may provide an anchorage to a transient noncovalent dimer, which maintains Cys31 and Cys32 of the two subunits in proximity, thus stabilizing a quaternary structure, similar to that found for the noncovalent swapped dimer of BSRNase, that allows the molecule to escape RI and/or to enhance the formation of the interchain disulfides. PMID:19177350

  4. Mixed-valence copper(I,II) complexes with 4-(1H-pyrazol-1-yl)-6-R-pyrimidines: from ionic structures to coordination polymers.

    Science.gov (United States)

    Vinogradova, Katerina A; Krivopalov, Viktor P; Nikolaenkova, Elena B; Pervukhina, Natalia V; Naumov, Dmitrii Yu; Boguslavsky, Evgenii G; Bushuev, Mark B

    2016-01-14

    Two pyrimidine-based ligands, 4-(3,5-diphenyl-1H-pyrazol-1-yl)-6-(morpholino)pyrimidine () and 4-(3,5-diphenyl-1H-pyrazol-1-yl)-6-phenoxypyrimidine (), and a series of mixed-valence copper(i,ii) halide complexes, [Cu(L(2))2Br]2[Cu2Br4] (), [Cu(L(2))2Cl][CuCl2] (), and [Cu2L(3)Br3]n (), have been synthesized. The complex [Cu(L(2))2Br]2[Cu2Br4] was prepared by the reaction of with CuBr2 in a 1 : 1 molar ratio in MeCN. Its chlorido-analogue, the complex [Cu(L(2))2Cl][CuCl2], was synthesized by the reaction between , CuCl2 and CuCl in a 2 : 1 : 1 molar ratio in MeCN. The ligand acts as a chelating one. In the structures of the complexes [Cu(L(2))2Br]2[Cu2Br4] and [Cu(L(2))2Cl][CuCl2] the Cu(2+) ion is in the cationic part of the complex whereas the Cu(+) ion is located in the anionic part. The best way to synthesize the mixed-valence 1D coordination polymer [Cu2L(3)Br3]n is to react CuBr2 with in a 2 : 1 molar ratio in the MeCN/CHCl3 mixture on heating. In the structure of [Cu2L(3)Br3]n the ligand shows chelating/bridging tridentate coordination. This is the first example of the tridentate coordination of 4-(1H-pyrazol-1-yl)-6-R-pyrimidines. The striking difference between the coordination behavior of and (chelating bidentate vs. chelating/bridging coordination) is related with the possibility of rotation of the 6-phenoxy group around the C-O bond which makes the N(1) pyrimidine atom less sterically hindered, enabling it to participate in metal ion binding. Importantly, all copper ions in [Cu2L(3)Br3]n show similar tetrahedral environments, CuNBr3 and CuN2Br2, which is extremely rare for mixed-valence copper(i,ii) compounds. The ligands and show blue emission which is quenched upon their coordination to copper ions. The 1D coordination polymer [Cu2L(3)Br3]n shows high thermal stability and unusual solvent-occlusion properties. The role of the substituents favoring the formation of the mixed-valence copper(i,ii) complexes with 4-(1H-pyrazol-1-yl)-6-R-pyrimidines

  5. Synthesis, and Fluorescence Properties of Coumarin and Benzocoumarin Derivatives Conjugated Pyrimidine Scaffolds for Biological Imaging Applications.

    Science.gov (United States)

    Al-Masoudi, Najim A; Al-Salihi, Niran J; Marich, Yossra A; Markus, Timo

    2015-11-01

    Series of coumarin and 5,6-benzomcomarin substituted pyrimidine derivatives 11-15 and 22-25 were synthesized, aiming to develop new imaging fluorescent agents. Analogously, treatment of 4-chloropyrimidine analog 16 with coumarin 3-carbohyrazide 5 under MWI condition followed by boiling with NH4OAc in HOAc furnished coumarin-1,2,4-triazolo-pyrimidine analog 18. The fluorescence property was investigated spectrophotometrically in MeOH with Rhodamine 6G as standard dye. All the compounds showed emission in the region between 331 and 495 nm. The quantum yield of all the compounds were found to be weak, except methyl benzocoumarin 3-carboxylate 22 which showed (ΦF = 0.98) in comparison to Rhodamine 6G as standard (ΦF = 0.95).

  6. Direct Isolation of Purines and Pyrimidines from Nucleic Acids Using Sublimation

    Science.gov (United States)

    Glavin, Daniel P.; Schubert, Michael; Bada, Jeffrey L.

    2003-01-01

    A sublimation technique was developed to isolate purines and pyrimidines directly from lambda-deoxyribonucleic acid (lambda-DNA) and Escherichia coli cells. The sublimation of adenine, cytosine, guanine, and thymine from lambda-DNA was tested under reduced pressure (approx. 0.5 Torr) at temperatures of >150 C. With the exception of guanine, approximately 60 -75% of each base was sublimed directly from the lambda-DNA and recovered on a coldfinger of the sublimation apparatus after heating to 450 C. Several nucleobases including adenine, cytosine, thymine, and uracil were also recovered from E. coli bacteria after heating the cells to the same temperature, although some thermal decomposition of the bases also occurred. These results demonstrate the feasibility of using sublimation to isolate purines and pyrimidines from native E. coli DNA and RNA without any chemical treatment of the cells.

  7. cis-Aquadichlorido[pyrimidin-2(1H-one-κN3]copper(II

    Directory of Open Access Journals (Sweden)

    A. Guy Orpen

    2008-07-01

    Full Text Available In the title compound, [CuCl2(C4H4N2O(H2O], the CuII cation is coordinated by two chloride anions, one pyrimidin-2-one N atom and one water molecule, giving a slightly distorted square-planar geometry. In the crystal structure, the pyrimidin-2-one rings stack along the b axis, with an interplanar distance of 3.306 Å, as do the copper coordination planes (interplanar spacing = 2.998 Å. The coordination around the Jahn–Teller-distorted CuII ion is completed by long Cu...O [3.014 (5 Å] and Cu...Cl [3.0194 (15 Å] interactions with adjacent molecules involved in this stacking. Several N—H...Cl, O—H...Cl and O—H...O intermolecular hydrogen bonds form a polar three-dimensional network.

  8. Amorphous Silica-Promoted Lysine Dimerization: a Thermodynamic Prediction

    Science.gov (United States)

    Kitadai, Norio; Nishiuchi, Kumiko; Nishii, Akari; Fukushi, Keisuke

    2017-08-01

    It has long been suggested that mineral surfaces played a crucial role in the abiotic polymerization of amino acids that preceded the origin of life. Nevertheless, it remains unclear where the prebiotic process took place on the primitive Earth, because the amino acid-mineral interaction and its dependence on environmental conditions have yet to be understood adequately. Here we examined experimentally the adsorption of L-lysine (Lys) and its dimer (LysLys) on amorphous silica over a wide range of pH, ionic strength, adsorbate concentration, and the solid/water ratio, and determined the reaction stoichiometries and the equilibrium constants based on the extended triple-layer model (ETLM). The retrieved ETLM parameters were then used, in combination with the equilibrium constant for the peptide bond formation in bulk water, to calculate the Lys-LysLys equilibrium in the presence of amorphous silica under various aqueous conditions. Results showed that the silica surface favors Lys dimerization, and the influence varies greatly with changing environmental parameters. At slightly alkaline pH (pH 9) in the presence of a dilute NaCl (1 mM), the thermodynamically attainable LysLys from 0.1 mM Lys reached a concentration around 50 times larger than that calculated without silica. Because of the versatility of the ETLM, which has been applied to describe a wide variety of biomolecule-mineral interactions, future experiments with the reported methodology are expected to provide a significant constraint on the plausible geological settings for the condensation of monomers to polymers, and the subsequent chemical evolution of life.

  9. 3-({5-Bromo-4-[pyrrolidin-1-yl]pyrimidin-2-yl}aminophenol

    Directory of Open Access Journals (Sweden)

    Alan M. Jones

    2015-05-01

    Full Text Available Re-investigation of the 1H-NMR spectrum reported for 15-bromo-4-oxa-2,9-diaza-1(2,4-pyrimidine-3(1,3-benzenacyclononaphane (2 prepared via a Mitsunobu- mediated macroether cyclisation led to a proposed structural isomer (3. The title compound (3 was prepared via a two-step protocol and assigned using 1H, 13C-NMR and LC-MS.

  10. A Facile Microwave-Assisted Synthesis of Some Fused Pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    S. A. Al-Issa

    2014-06-01

    Full Text Available The highly accelerated synthesis of thienopyrimidinones, theino- pyrimidines,thioxotheinopyrimidinones and a thienotriazolopyrimidinone derivatives under microwave irradiation is reported. Compared to conventional conditions, microwaves method offered several advantage likes short time, good yields, simple procedure, mild conditions and easy workup. The structure of synthesized compounds have been characterized on the basis of their elemental analysis and spectral data, and screened for their antimicrobial activity.

  11. Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis.

    Science.gov (United States)

    Rabinovich, Shiran; Adler, Lital; Yizhak, Keren; Sarver, Alona; Silberman, Alon; Agron, Shani; Stettner, Noa; Sun, Qin; Brandis, Alexander; Helbling, Daniel; Korman, Stanley; Itzkovitz, Shalev; Dimmock, David; Ulitsky, Igor; Nagamani, Sandesh C S; Ruppin, Eytan; Erez, Ayelet

    2015-11-19

    Cancer cells hijack and remodel existing metabolic pathways for their benefit. Argininosuccinate synthase (ASS1) is a urea cycle enzyme that is essential in the conversion of nitrogen from ammonia and aspartate to urea. A decrease in nitrogen flux through ASS1 in the liver causes the urea cycle disorder citrullinaemia. In contrast to the well-studied consequences of loss of ASS1 activity on ureagenesis, the purpose of its somatic silencing in multiple cancers is largely unknown. Here we show that decreased activity of ASS1 in cancers supports proliferation by facilitating pyrimidine synthesis via CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, and dihydroorotase complex) activation. Our studies were initiated by delineating the consequences of loss of ASS1 activity in humans with two types of citrullinaemia. We find that in citrullinaemia type I (CTLN I), which is caused by deficiency of ASS1, there is increased pyrimidine synthesis and proliferation compared with citrullinaemia type II (CTLN II), in which there is decreased substrate availability for ASS1 caused by deficiency of the aspartate transporter citrin. Building on these results, we demonstrate that ASS1 deficiency in cancer increases cytosolic aspartate levels, which increases CAD activation by upregulating its substrate availability and by increasing its phosphorylation by S6K1 through the mammalian target of rapamycin (mTOR) pathway. Decreasing CAD activity by blocking citrin, the mTOR signalling, or pyrimidine synthesis decreases proliferation and thus may serve as a therapeutic strategy in multiple cancers where ASS1 is downregulated. Our results demonstrate that ASS1 downregulation is a novel mechanism supporting cancerous proliferation, and they provide a metabolic link between the urea cycle enzymes and pyrimidine synthesis.

  12. Dichloridobis[2-methyl-sulfanyl-4-(pyridin-2-yl)pyrimidine-κN,N]cobalt(II).

    Science.gov (United States)

    Yang, Wen-Na

    2011-09-01

    The asymmetric unit of the title compound, [CoCl(2)(C(10)H(9)N(3)S)(2)], contains one half-mol-ecule with the Co(II) atom situtated on a twofold rotational axis. The Co(II) atom, in an octa-hedral enviroment, is coordinated by four N atoms from two 2-methyl-sulfanyl-4-(pyridin-2-yl)pyrimidine ligands and two Cl atoms.

  13. Metal enhanced fluorescence of Ag-nanoshell dimer

    Science.gov (United States)

    Liaw, Jiunn-Woei; Chen, Huang-Chih; Chen, Bae-Renn; Kuo, Mao-Kuen

    2014-04-01

    The plasmon modes of Ag-nanoshell dimer on metal enhanced fluorescence (MEF) are studied theoretically. The amplified excitation rate of a dimer (two identical Ag nanoshells) illuminated by a plane wave for exciting a molecule located at the gap center is calculated. Subsequently, the apparent quantum yield of the emission of the excited molecule affected by the dimer is investigated. The multiple multipole method is used for the both simulations. Finally, the enhancement factor of the dimer on the overall photoluminescence of the molecule in terms of the two parameters is evaluated. Our results show that Ag-nanoshell dimer is a dual-band photoluminescence enhancer for MEF at the bonding dipole and quadrupole modes. The former is broadband, and the latter narrowband. Both bands depend on the gap size. Moreover, the average enhancement factor of Ag-nanoshell dimer for MEF with a Stokes shift is discussed.

  14. Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Velázquez-Olvera Stephania

    2012-08-01

    Full Text Available Abstract Background Imidazo[1,2-a]pyridines and pyrimidines are important organic fluorophores which have been investigated as biomarkers and photochemical sensors. The effect on the luminescent property by substituents in the heterocycle and phenyl rings, have been studied as well. In this investigation, series of 3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines were synthesized and evaluated in relation to fluorescence emission, based upon the hypothesis that the hydroxymethyl group may act as an enhancer of fluorescence intensity. Results Compounds of both series emitted light in organic solvents dilutions as well as in acidic and alkaline media. Quantitative fluorescence spectroscopy determined that both fused heterocycles fluoresced more intensely than the parent unsubstituted imidazo[1,2-a]azine fluorophore. In particular, 3-hydroxymethyl imidazo[1,2-a]pyridines fluoresced more intensely than 3-hydroxymethyl imidazo[1,2-a]pyrimidines, the latter emitting blue light at longer wavelengths, whereas the former emitted purple light. Conclusion It was concluded that in most cases the hydroxymethyl moiety did act as an enhancer of the fluorescence intensity, however, a comparison made with the fluorescence emitted by 2-aryl imidazo[1,2-a]azines revealed that in some cases the hydroxymethyl substituent decreased the fluorescence intensity.

  15. Absolute cross sections for electronic excitation of pyrimidine by electron impact

    Energy Technology Data Exchange (ETDEWEB)

    Regeta, Khrystyna; Allan, Michael [Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg (Switzerland); Mašín, Zdeněk [Max-Born Institute for Nonlinear Optics and Short Pulse Spectroscopy, Max-Born-Straße 2A, 12489 Berlin (Germany); Gorfinkiel, Jimena D. [Department of Physical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA (United Kingdom)

    2016-01-14

    We measured differential cross sections for electron-impact electronic excitation of pyrimidine, both as a function of electron energy up to 18 eV, and of scattering angle up to 180°. The emphasis of the present work is on recording detailed excitation functions revealing resonances in the excitation process. The differential cross sections were summed to obtain integral cross sections. These are compared to results of R-matrix calculations, which successfully reproduce both the magnitude of the cross section and the major resonant features. Comparison of the experiment to the calculated contributions of different symmetries to the integral cross section permitted assignment of several features to specific core-excited resonances. Comparison of the resonant structure of pyrimidine with that of benzene revealed pronounced similarities and thus a dominant role of π–π{sup ∗} excited states and resonances. Electron energy loss spectra were measured as a preparation for the cross section measurements and vibrational structure was observed for some of the triplet states. A detailed analysis of the electronic excited states of pyrimidine is also presented.

  16. Isolation of Purines and Pyrimidines from the Murchison Meteorite Using Sublimation

    Science.gov (United States)

    Glavin, D. P.; Bada, J. L.

    2004-01-01

    The origin of life on Earth, and possibly on other planets such as Mars, would have required the presence of liquid water and a continuous supply of prebiotic organic compounds. The exogenous delivery of organic matter by asteroids, comets, and carbonaceous meteorites could have contributed to the early Earth s prebiotic inventory by seeding the planet with biologically important organic compounds. A wide variety of prebiotic organic compounds have previously been detected in the Murchison CM type carbonaceous chondrite including amino acids, purines and pyrimidines. These compounds dominate terrestrial biochemistry and are integral components of proteins, DNA and RNA. Several purines including adenine, guanine, hypoxanthine, and xanthine, as well as the pyrimidine uracil, have previously been detected in water or formic acid extracts of Murchison using ion-exclusion chromatography and ultraviolet spectroscopy. However, even after purification of these extracts, the accurate identification and quantification of nucleobases is difficult due to interfering UV absorbing compounds. In order to reduce these effects, we have developed an extraction technique using sublimation to isolate purines and pyrimidines from other non-volatile organic compounds in Murchison acid extracts.

  17. Intermediate energy cross sections for electron-impact vibrational-excitation of pyrimidine

    Energy Technology Data Exchange (ETDEWEB)

    Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia); Ellis-Gibbings, L.; García, G. [Instituto de Física Fundamental, CSIC, Serrano 113-bis, 28006 Madrid (Spain); Nixon, K. L. [Departamento de Física, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, Minas Gerais (Brazil); School of Biology, Chemistry and Forensic Science, University of Wolverhampton, Wolverhampton WV1 1LY (United Kingdom); Lopes, M. C. A. [Departamento de Física, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, Minas Gerais (Brazil); Brunger, M. J., E-mail: Michael.Brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2015-09-07

    We report differential cross sections (DCSs) and integral cross sections (ICSs) for electron-impact vibrational-excitation of pyrimidine, at incident electron energies in the range 15–50 eV. The scattered electron angular range for the DCS measurements was 15°–90°. The measurements at the DCS-level are the first to be reported for vibrational-excitation in pyrimidine via electron impact, while for the ICS we extend the results from the only previous condensed-phase study [P. L. Levesque, M. Michaud, and L. Sanche, J. Chem. Phys. 122, 094701 (2005)], for electron energies ⩽12 eV, to higher energies. Interestingly, the trend in the magnitude of the lower energy condensed-phase ICSs is much smaller when compared to the corresponding gas phase results. As there is no evidence for the existence of any shape-resonances, in the available pyrimidine total cross sections [Baek et al., Phys. Rev. A 88, 032702 (2013); Fuss et al., ibid. 88, 042702 (2013)], between 10 and 20 eV, this mismatch in absolute magnitude between the condensed-phase and gas-phase ICSs might be indicative for collective-behaviour effects in the condensed-phase results.

  18. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    Science.gov (United States)

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  19. Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.

    Science.gov (United States)

    Phan, Andy; Mailey, Katherine; Sakai, Jessica; Gu, Xiaobo; Schroeder, Susan J

    2017-02-17

    Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased towards small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with more than 6 nucleotides that occur frequently in viral RNA. This paper presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Protonated cytosine and uracil base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with more than 6 nucleotides are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2x2 have been measured (Mathews 2004). These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites.

  20. SYNTHESIS AND BIOLOGICAL ACTIVITY OF IMIDAZOLE DERIVED CHALCONES AND IT’S PYRIMIDINES

    Directory of Open Access Journals (Sweden)

    Pavan Kumar Padarthi

    2013-06-01

    Full Text Available Microbial contribution increasing rapidly due to invasion by the pathogenic organisms like bacteria, fungi and virus in the present disease burden of human health. To treat these diseases many potent and broad spectrum antibiotics were discovered e.g., ampicillin, amoxicillin, carbenicillin, ofloxacin and tetracycline etc., Even though antibiotics are life saving drugs in therapeutics but they are potentially harmful. These harmful effects include allergic and anaphylactic reaction, development of resistance, destruction of normal non-pathogenic bacterial flora and selective toxicity like aplastic anemia, kidney damage. As the microbial resistance make anti-microbial therapy very complex, there is a definite need of novel anti-microbials or drugs for combination therapy with standard antibiotics. Our aim was to synthesize and explore the anti-microbial activity of chalcones and its derived pyrimidines against various pathological micro organisms. Novel imidazole derived chalcones were synthesized and characterization was carried out by analyzing melting point, IR, 1H NMR data. The synthesized chalcones and pyrimidines are tested for their antimicrobial activity against various bacteria as well as fungi. Further synthesis of novel heterocyclic chalcones, structural elucidation, spectral analysis, biological activity of synthesized chalcones and its derived pyrimidines gives a hope for enhanced biological action using QSAR Studies.

  1. Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria

    Science.gov (United States)

    Yoon, Heeyong; Zhang, Yan; Pain, Jayashree; Lyver, Elise R.; Lesuisse, Emmanuel; Pain, Debkumar; Dancis, Andrew

    2016-01-01

    Mitochondria transport and utilize iron for the synthesis of haem and Fe–S clusters. Although many proteins are known to be involved in these processes, additional proteins are likely to participate. To test this hypothesis, in the present study we used a genetic screen looking for yeast mutants that are synthetically lethal with the mitochondrial iron carriers Mrs3 and Mrs4. Several genes were identified, including an isolate mutated for Yfh1, the yeast frataxin homologue. All such triple mutants were complemented by increased expression of Rim2, another mitochondrial carrier protein. Rim2 overexpression was able to enhance haem and Fe–S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds. Conversely Rim2 depletion impaired haem and Fe–S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds, indicating a unique requirement for this mitochondrial transporter for these processes. Rim2 was previously shown to mediate pyrimidine exchange in and out of vesicles. In the present study we found that isolated mitochondria lacking Rim2 exhibited concordant iron defects and pyrimidine transport defects, although the connection between these two functions is not explained. When organellar membranes were ruptured to bypass iron transport, haem synthesis from added iron and porphyrin was still markedly deficient in Rim2-depleted mitochondrial lysate. The results indicate that Rim2 is a pyrimidine exchanger with an additional unique function in promoting mitochondrial iron utilization. PMID:21777202

  2. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.

    Science.gov (United States)

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2016-06-01

    Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.

  3. Thermodynamic properties for the sodium dimer

    Science.gov (United States)

    Song, Xiao-Qin; Wang, Chao-Wen; Jia, Chun-Sheng

    2017-04-01

    We present a closed-form expression of the classical vibrational partition function for the improved Rosen-Morse potential energy model. We give explicit expressions for the vibrational mean energy, vibrational specific heat, vibrational free energy, and vibrational entropy for diatomic molecule systems. The properties of these thermodynamic functions for the Na2 dimer are discussed in detail. We find that the improved Rosen-Morse potential model is superior to the harmonic oscillator in calculating the heat capacity for the Na2 molecules.

  4. Thermodynamics of acetylene van der Waals dimerization

    Science.gov (United States)

    Colussi, A. J.; Sander, S. P.; Friedl, R. R.

    1991-01-01

    Integrated band intensities of the 620/cm absorption in (C2H2)2 are measured by FTIR spectroscopy at constant acetylene pressure between 198 and 273 K. These data, in conjunction with ab initio results for (C2H2)2, are used for the statistical evaluation of the equilibrium constant Kp(T) for acetylene-cluster dimerization. The present results are used to clarify the role of molecular clusters in chemical systems at or near equilibrium, in particular in Titan's stratosphere.

  5. The properties of dimers confined between two charged plates.

    Science.gov (United States)

    Hatlo, Marius M; Bohinc, Klemen; Lue, Leo

    2010-03-21

    We consider two like-charged planar surfaces immersed in solution of oppositely charged dimer counterions with a bond length l. To analyze this system, we extend and employ a self-consistent field theory that has been shown to be accurate from the weak to the intermediate through to the strong coupling regimes. In the limit of very short dimers, the results converge to the results for pointlike divalent ions. Near the surfaces, the dimers lie parallel to the charged plates. In the intermediate coupling regime, the dimers are aligned perpendicularly to the surface when they are a distance l from a surface. In the weak coupling regime, the interactions are only repulsive. At slightly higher couplings, there is a minimum in the variation of the free energy with distance at approximately the bond length of the dimers, which arises from bridging conformations of the dimers. In the intermediate coupling regime, an additional minimum in the free energy is observed at much smaller distances, which is due to the correlations between the dimers. For large dimer bond lengths, this minimum is metastable with respect to the previous minimum. However, as the bond length decreases, this minimum becomes the stable, while the minimum associated with the dimer bond length becomes metastable and eventually disappears. For shorter dimer bond length the attractive interaction is the result of correlations between counterions and charges on the surfaces. We find that dimers can mediate attractive interaction between like-charged surfaces in the intermediate coupling regime. The analysis of orientations confirms the bridging mechanism for sufficiently long dimers, whereas at high electrostatic couplings charge correlations contribute to the attraction.

  6. Rotational spectra of propargyl alcohol dimer: A dimer bound with three different types of hydrogen bonds

    Energy Technology Data Exchange (ETDEWEB)

    Mani, Devendra; Arunan, E., E-mail: arunan@ipc.iisc.ernet.in [Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012 (India)

    2014-10-28

    Pure rotational spectra of the propargyl alcohol dimer and its three deuterium isotopologues have been observed in the 4 to 13 GHz range using a pulsed-nozzle Fourier transform microwave spectrometer. For the parent dimer, a total of 51 transitions could be observed and fitted within experimental uncertainty. For two mono-substituted and one bi-substituted deuterium isotopologues, a total of 14, 17, and 19 transitions were observed, respectively. The observed rotational constants for the parent dimer [A = 2321.8335(4) MHz, B = 1150.4774(2) MHz, and C = 1124.8898(2) MHz] are close to those of the most stable structure predicted by ab initio calculations. Spectra of the three deuterated isotopologues and Kraitchman analysis positively confirm this structure. Geometrical parameters and “Atoms in Molecules” analysis on the observed structure reveal that the two propargyl alcohol units in the dimer are bound by three different types of hydrogen bonds: O–H⋯O, O–H⋯π, and C–H⋯π. To the best of our knowledge, propargyl alcohol seems to be the smallest molecule forming a homodimer with three different points of contact.

  7. Synthesis of Symmetrical Biaryls via Rhodium Catalyzed Dimerization of Arylmercurials and Mechanism of the Dimerization

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of symmetrical biaryls was synthesized from arylmercuric chlorides and biarylmercurials in the presence of [ClRh(CO)2]2 in hexamethylphosphoramide(HMPA). The mechanism of the [ClRh(CO)2]2 catalyzed dimerization of biarylmercurials was studied, and shown to be mainly intermolecular reaction.

  8. Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yosuke; Ishikawa, Rie; Sakatani, Toshio [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Ichinose, Junji [Department of Cardiothoracic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Sunohara, Mitsuhiro; Watanabe, Kousuke; Kage, Hidenori [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Nakajima, Jun [Department of Cardiothoracic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Nagase, Takahide; Ohishi, Nobuya [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Takai, Daiya, E-mail: dtakai-ind@umin.ac.jp [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Department of Clinical Laboratory, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)

    2015-02-13

    Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can arise from anywhere in the body. Anaplastic lymphoma kinase (ALK) gene rearrangements, most often resulting in the tropomyosin 3 (TPM3)-ALK fusion gene, are the main causes of IMT. However, the mechanism of malignant transformation in IMT has yet to be elucidated. The purpose of this study was to clarify the role of the TPM3 region in the transformation of IMT via TPM3-ALK. Lentivirus vectors containing a TPM3-ALK fusion gene lacking various lengths of TPM3 were constructed and expressed in HEK293T and NIH3T3 cell lines. Focus formation assay revealed loss of contact inhibition in NIH3T3 cells transfected with full-length TPM3-ALK, but not with ALK alone. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) revealed that TPM3-ALK dimerization increased in proportion to the length of TPM3. Western blot showed phosphorylation of ALK, ERK1/2, and STAT3 in HEK293T cells transfected with TPM3-ALK. Thus, the coiled-coil structure of TPM3 contributes to the transforming ability of the TPM3-ALK fusion protein, and longer TPM3 region leads to higher dimer formation. - Highlights: • TPM3-ALK fusion protein dimerizes through the coiled-coil structure of TPM3. • Longer coiled-coil structure of TPM3 leads to higher TPM3-ALK dimer formation. • Presence of TPM3-ALK dimer leads to ALK, STAT3, and ERK1/2 phosphorylation. • Presence of TPM3-ALK leads to loss of contact inhibition. • BN-PAGE is a simple technique for visualizing oncogenic dimerization.

  9. Disordered clusters of Bak dimers rupture mitochondria during apoptosis

    Science.gov (United States)

    Uren, Rachel T; O’Hely, Martin; Iyer, Sweta; Bartolo, Ray; Shi, Melissa X; Brouwer, Jason M; Alsop, Amber E; Dewson, Grant; Kluck, Ruth M

    2017-01-01

    During apoptosis, Bak and Bax undergo major conformational change and form symmetric dimers that coalesce to perforate the mitochondrial outer membrane via an unknown mechanism. We have employed cysteine labelling and linkage analysis to the full length of Bak in mitochondria. This comprehensive survey showed that in each Bak dimer the N-termini are fully solvent-exposed and mobile, the core is highly structured, and the C-termini are flexible but restrained by their contact with the membrane. Dimer-dimer interactions were more labile than the BH3:groove interaction within dimers, suggesting there is no extensive protein interface between dimers. In addition, linkage in the mobile Bak N-terminus (V61C) specifically quantified association between dimers, allowing mathematical simulations of dimer arrangement. Together, our data show that Bak dimers form disordered clusters to generate lipidic pores. These findings provide a molecular explanation for the observed structural heterogeneity of the apoptotic pore. DOI: http://dx.doi.org/10.7554/eLife.19944.001 PMID:28182867

  10. Pathogenic Cysteine Removal Mutations in FGFR Extracellular Domains Stabilize Receptor Dimers and Perturb the TM Dimer Structure.

    Science.gov (United States)

    Sarabipour, Sarvenaz; Hristova, Kalina

    2016-10-09

    Missense mutations that introduce or remove cysteine residues in receptor tyrosine kinases are believed to cause pathologies by stabilizing the active receptor tyrosine kinase dimers. However, the magnitude of this stabilizing effect has not been measured for full-length receptors. Here, we characterize the dimer stabilities of three full-length fibroblast growth factor receptor (FGFR) mutants harboring pathogenic cysteine substitutions: the C178S FGFR1 mutant, the C342R FGFR2 mutant, and the C228R FGFR3 mutant. We find that the three mutations stabilize the FGFR dimers. We further see that the mutations alter the configuration of the FGFR transmembrane dimers. Thus, both aberrant dimerization and perturbed dimer structure likely contribute to the pathological phenotypes arising due to these mutations.

  11. Dimeric Labdane Diterpenes: Synthesis and Antiproliferative Effects

    Directory of Open Access Journals (Sweden)

    Guillermo Schmeda-Hirschmann

    2013-05-01

    Full Text Available Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The aim of the present work was to synthesize dimeric diterpenes from the labdane imbricatolic acid using esters, ethers and the triazole ring as linkers. Some 18 new derivatives were prepared and the compounds were evaluated for antiproliferative activity on human normal fibroblasts (MRC-5 and the following human tumor cell lines: AGS, SK-MES-1, J82 and HL-60. The diethers 8–10, differing in the number of CH2 units in the linker, presented better antiproliferative activity with a maximum effect for the derivative 9. The best antiproliferative effect against HL-60 cells was found for compounds 3 and 17, with IC50 values of 22.3 and 23.2 μM, lower than that found for the reference compound etoposide (2.23 μM. The compounds 9, 17 and 11 were the most active derivatives towards AGS cells with IC50 values of 17.8, 23.4 and 26.1 μM. A free carboxylic acid function seems relevant for the effect as several of the compounds showed less antiproliferative effect after methylation.

  12. Water dimer absorption of visible light

    Directory of Open Access Journals (Sweden)

    J. Hargrove

    2007-07-01

    Full Text Available Laboratory measurements of water vapor absorption using cavity ring-down spectroscopy revealed a broad absorption at 405 nm with a quadratic dependence on water monomer concentration, a similar absorption with a linear component at 532 nm, and only linear absorption at 570 nm in the vicinity of water monomer peaks. D2O absorption is weaker and linear at 405 nm. Van't Hoff plots constructed at 405.26 nm suggest that for dimerization, Keq=0.056±0.02 atm−1, ΔH°301 K=−16.6±2 kJ mol−1 and ΔS°301 K=−80±10 J mol−1 K−1. This transition peaks at 409.5 nm, could be attributed to the 8th overtone of water dimer and the 532 nm absorption to the 6th overtone. It is possible that some lower overtones previously searched for are less enhanced. These absorptions could increase water vapor feed back calculations leading to higher global temperature projections with currently projected greenhouse gas levels or greater cooling from greenhouse gas reductions.

  13. Modelling study of dimerization in mammalian defensins

    Directory of Open Access Journals (Sweden)

    Verma Chandra

    2006-12-01

    Full Text Available Abstract Background Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics. Results Based on homology greater than 40%, structural models of 8 homologs of HBD-2 were constructed. A conserved pattern of electrostatics and dynamics was observed across 6 of the examined defensins; models backed by energetics suggest that the defensins in these 6 organisms are characterized by dimerization-linked enhanced functional potentials. In contrast, dimerization is not energetically favoured in the sheep, goat and mouse defensins, suggesting that they function efficiently as monomers. Conclusion β-defensin 2 from some mammals may work as monomers while those in others, including humans, work as oligomers. This could potentially be used to design human defensins that may be effective at lower concentrations and hence have therapeutic benefits.

  14. Establishment and characterization of melanoma cell line from a xeroderma pigmentosum patient: activation of N-ras at a potential pyrimidine dimer site.

    NARCIS (Netherlands)

    W. Keijzer; M.P. Mulder; J.C.M. Langeveld; E.M.E. Smit (Elisabeth); J.L. Bos; D. Bootsma (Dirk); J.H.J. Hoeijmakers (Jan)

    1989-01-01

    textabstractPatients suffering from the genetic disorder xeroderma pigmentosum (XP) display an extreme sensitivity of their skin to sun (UV) exposure and predisposition to skin cancer due to deficiencies in the excision DNA repair pathway. Here we describe the establishment and characterization of t

  15. Rh-Catalyzed, Regioselective, C-H Bond Functionalization: Access to Quinoline-Branched Amines and Dimers.

    Science.gov (United States)

    Reddy, M Damoder; Fronczek, Frank R; Watkins, E Blake

    2016-11-04

    Rh-catalyzed, chelation-induced, C-5 regioselective C-H functionalization of 8-amidoquinolines with a range of N-Boc aminals is reported for the first time. The addition of in situ generated imines to C(sp(2))-H bonds afforded branched amines in good to excellent yields. Moreover, this transformation features good functional group compatibility, broad substrate scope, and mild reaction conditions and is suitable for gram-scale synthesis. In addition, an unprecedented, chelation-induced, site-selective, remote dimerization of quinolines led to the formation of dimer frameworks in moderate yields under Rh-catalyzed conditions.

  16. 3D nanostar dimers with a sub-10-nm gap for single-/few-molecule surface-enhanced raman scattering

    KAUST Repository

    Chirumamilla, Manohar

    2014-01-22

    Plasmonic nanostar-dimers, decoupled from the substrate, have been fabricated by combining electron-beam lithography and reactive-ion etching techniques. The 3D architecture, the sharp tips of the nanostars and the sub-10 nm gap size promote the formation of giant electric-field in highly localized hot-spots. The single/few molecule detection capability of the 3D nanostar-dimers has been demonstrated by Surface-Enhanced Raman Scattering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Structure and dimerization of translation initiation factor aIF5B in solution

    Energy Technology Data Exchange (ETDEWEB)

    Carø VohlanderRasmussen, Louise; Oliveira, Cristiano Luis Pinto; Byron, Olwyn; Jensen, Janni Mosgaard; Pedersen, Jan Skov; Sperling-Petersen, Hans Uffe; Mortensen, Kim Kusk (Aarhus); (Glasgow)

    2012-02-07

    Translation initiation factor 5B (IF5B) is required for initiation of protein synthesis. The solution structure of archaeal IF5B (aIF5B) was analysed by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) and was indicated to be in both monomeric and dimeric form. Sedimentation equilibrium (SE) analytical ultracentrifugation (AUC) of aIF5B indicated that aIF5B forms irreversible dimers in solution but only to a maximum of 5.0-6.8% dimer. Sedimentation velocity (SV) AUC at higher speed also indicated the presence of two species, and the sedimentation coefficients s{sub 20,w}{sup 0} were determined to be 3.64 and 5.51 {+-} 0.29 S for monomer and dimer, respectively. The atomic resolution (crystallographic) structure of aIF5B (Roll-Mecak et al. [6]) was used to model monomer and dimer, and theoretical sedimentation coefficients for these models were computed (3.89 and 5.63 S, respectively) in good agreement with the sedimentation coefficients obtained from SV analysis. Thus, the structure of aIF5B in solution must be very similar to the atomic resolution structure of aIF5B. SAXS data were acquired in the same buffer with the addition of 2% glycerol to inhibit dimerization, and the resultant monomeric aIF5B in solution did indeed adopt a structure very similar to the one reported earlier for the protein in crystalline form. The p(r) function indicated an elongated conformation supported by a radius of gyration of 37.5 {+-} 0.2 {angstrom} and a maximum dimension of {approx}130 {angstrom}. The effects of glycerol on the formation of dimers are discussed. This new model of aIF5B in solution shows that there are universal structural differences between aIF5B and the homologous protein IF2 from Escherichia coli.

  18. HBc二聚体组装核衣壳相关功能域突变对HBV复制的影响%The effect of mutation of hepatitis B virus core protein dimer interface domain related to nucleocapsid formation on HBV replication

    Institute of Scientific and Technical Information of China (English)

    邓凯; 蒋栋; 韩进超; 潘孝本; 王豪; 魏来

    2010-01-01

    Objective To investigate the effect of hepatitis B virus core protein (HBc) dimer interfaces amino acids mutation on nucleocapsid assembly and HBV DNA replication. Methods Based on HBc three dimension structure, four HBc dimer interfaces domain mutation plasmids, pHBc14-18M,pHBc120-135M,pHBc23-39M and pHBc122-139M were constructed in pcDNA3.1 vector by PCR site-directed mutagenesis, there was a flag-tag at the C-terminal of all mutants for easy detection. Wild type core protein plasmid 1-183flag was also constructed as a positive control. The 4 mutants were cotransfected HepG2 cells with pHBV1.2 core negative plasmid (pHBV1.2-core-) ,which contained 1.2 copies of HBV whole genome but the core protein would not express due to a stop codon. The capsid formation, HBV pregenome(pgRNA) and HBV DNA replication mediate were analyzed by native agarose gel electrophoresis and Western blot, Northern blot and Southern blot , respectively. The 4 mutants were also cotransfected HepG2 cells with HBV wild type plasmid pHBV1.2 and examined by Southern blot. Virions in the medium were determined by native agarose gel electrophoresis and Western blot. Results Cotransfecting HepG2 cells with pHBV1.2-core- plasmid, pHBc14-18M,pHBc120-135M and pHBc122-139M mutant groups formed nucleocapsid-like structure but pHBc23-39M could not, Northern and Southern blot displayed no signal in all mutants except 1-183flag conrol group. In pHBV1.2 cotransfection experiment, HBV DNA replication was blocked in pHBc14-18M, pHBc120-135M and pHBc122-139M mutant groups, sharply decreased in pHBc120-135M and pHBc122-139M groups, correspondingly virons production in medium were also inhibited. pHBc23-39M mutant exerted no influence on HBV replication. Conclusion pHBc23-39M mutant can neither form nucleocapsid-like structure nor interact with wild type HBc dimmer to interfere HBV replication.On the contrast, pHBc14-18M, pHBc120-135M and pHBc122-139M mutants can form nucleocapsid-like structure by themselves

  19. Synthesis and Antimicrobial Activity of Some New Pyrazole, Fused Pyrazolo[3,4-d]-pyrimidine and Pyrazolo[4,3-e][1,2,4]- triazolo[1,5-c]pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Omar A. Miqdad

    2008-07-01

    Full Text Available Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3Hone and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16a,b and 17a,b. Reactions of compounds 17a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19a,b, respectively.

  20. On couplings and excimers: lessons from studies of singlet fission in covalently linked tetracene dimers.

    Science.gov (United States)

    Feng, Xintian; Krylov, Anna I

    2016-03-21

    Electronic factors controlling singlet fission (SF) rates are investigated in covalently linked dimers of tetracene. Using covalent linkers, relative orientation of the individual chromophores can be controlled, maximizing the rates of SF. Structures with coplanar and staggered arrangements of tetracene moieties are considered. The electronic structure calculations and three-state kinetic model for SF rates provide explanations for experimentally observed low SF yields in coplanar dimers and efficient SF in staggered dimers. The calculations illuminate the role of the excimer formation in SF process. The structural relaxation in the S1 state leads to the increased rate of the multi-exciton (ME) state formation, but impedes the second step, separation of the ME state into independent triplets. The slower second step reduces SF yield by allowing other processes, such as radiationless relaxation, to compete with triplet generation. The calculations of electronic couplings also suggest an increased rate of radiationless relaxation at the excimer geometries. Thus, the excimer serves as a trap of the ME state. The effect of covalent linkers on the electronic factors and SF rates is investigated. In all considered structures, the presence of the linker leads to larger couplings, however, the effect on the overall rate is less straightforward, since the linkers generally result in less favorable energetics. This complex behavior once again illustrates the importance of integrative approaches that evaluate the overall rate, rather than focusing on specific electronic factors such as energies or couplings.

  1. Stability improvement of the Nieuwland catalyst in the dimerization of acetylene to monovinylacetylene

    Institute of Scientific and Technical Information of China (English)

    Jianguo Liu; Yizan Zuo; Minghan Han; Zhanwen Wang; Dezheng Wang

    2012-01-01

    In the process of dimerization of acetylene to produce monovinylacetylene (MVA),the loss of active component CuCl in the Nieuwland catalyst due to the formation of a dark red precipitate was investigated.The formula of the precipitate was CuCl·2C2H2·1/5NH3,and it was presumed to be formed by the combination of NH3,C2H2 and [Cu]-acetylene π-complex,which was an intermediate in the dimerization reaction.The addition of hydrochloric acid into the catalyst can reduce the formation of precipitate,whereas excessive H+ is unfavorable to the dimerization reaction of acetylene.To balance between high acetylene conversion and low loss rate of CuCl,the optimum mass percentage of HCl in the added hydrochloric acid was determined.The result showed the optimum mass percentage of HCl decreased from 5.0% to 3.2% when the space velocity of acetylene was from 140 h-1 to 360 h-1.The result in this work also indicated the pH of the Nieuwland catalyst should be kept in the range of 5.80-5.97 during the reaction process,which was good for both catalyst life and acetylene conversion.

  2. UV-Light Exposure of Insulin: Pharmaceutical Implications upon Covalent Insulin Dityrosine Dimerization and Disulphide Bond Photolysis

    OpenAIRE

    Manuel Correia; Maria Teresa Neves-Petersen; Per Bendix Jeppesen; Søren Gregersen; Steffen B Petersen

    2012-01-01

    In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2)) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furtherm...

  3. Ultraviolet photodissociation of the van der Waals dimer (CH3I)(2) revisited. II. Pathways giving rise to neutral molecular iodine

    NARCIS (Netherlands)

    Vidma, K.V.; Baklanov, A.V.; Zhang, Y.W.; Parker, D.H.

    2006-01-01

    The formation of neutral I-2 by the photodissociation of the methyl iodide dimer, (CH3I)(2), excited within the A band at 249.5 nm is evaluated using velocity map imaging. In previous work [J. Chem. Phys. 122, 204301 (2005)], we showed that the formation of I-2(+) from photodissociation of the

  4. Coexistence and competition of on-site and intersite Coulomb interactions in Mott-molecular-dimers

    Science.gov (United States)

    Juliano, R. C.; de Arruda, A. S.; Craco, L.

    2016-02-01

    We reveal the interplay between on-site (U) and intersite (V) Coulomb interactions in the extended two-site Hubbard model. Due to its atomic-like form quantum correlations intrinsic to Mott-molecular-dimers are exactly computed. Our results for physical quantities such as double occupancy and specific heat are consistent with those obtained for the one-band Hubbard model, suggesting that a two-site dimer model is able to capture the essential thermodynamic properties of strongly interacting electron systems. It is noted that intersite Coulomb interactions promote the formation of doublons, which compete with the spin-singlet state induced by the on-site Coulomb repulsion. Our results are expected to be relevant for understanding electronic and thermodynamical properties of interacting electrons in systems with strongly coupled magnetic atoms.

  5. Dimerization of complement factor H-related proteins modulates complement activation in vivo.

    Science.gov (United States)

    Goicoechea de Jorge, Elena; Caesar, Joseph J E; Malik, Talat H; Patel, Mitali; Colledge, Matthew; Johnson, Steven; Hakobyan, Svetlana; Morgan, B Paul; Harris, Claire L; Pickering, Matthew C; Lea, Susan M

    2013-03-19

    The complement system is a key component regulation influences susceptibility to age-related macular degeneration, meningitis, and kidney disease. Variation includes genomic rearrangements within the complement factor H-related (CFHR) locus. Elucidating the mechanism underlying these associations has been hindered by the lack of understanding of the biological role of CFHR proteins. Here we present unique structural data demonstrating that three of the CFHR proteins contain a shared dimerization motif and that this hitherto unrecognized structural property enables formation of both homodimers and heterodimers. Dimerization confers avidity for tissue-bound complement fragments and enables these proteins to efficiently compete with the physiological complement inhibitor, complement factor H (CFH), for ligand binding. Our data demonstrate that these CFHR proteins function as competitive antagonists of CFH to modulate complement activation in vivo and explain why variation in the CFHRs predisposes to disease.

  6. Mitochondria localization and dimerization are required for CIDE-B to induce apoptosis.

    Science.gov (United States)

    Chen, Z; Guo, K; Toh, S Y; Zhou, Z; Li, P

    2000-07-28

    Cell death-inducing DFF45-like effector (CIDE)-B is a member of the novel family of apoptosis-inducing factors that share homology with the N-terminal region of DFF, the DNA fragmentation factor. The molecular mechanism of CIDE-B-induced apoptosis is unclear. We have shown here that CIDE-B protein is localized in mitochondria and forms homodimers and heterodimers with other family members. Serial deletion analyses suggest that the mitochondria localization signal and dimerization interface are overlapped and localized to the 30 amino acid residues at the C-terminal region of CIDE-B. Mitochondria localization and dimerization are both required for CIDE-B-induced apoptosis. Our study has thus revealed a mechanism for CIDE-B-induced apoptosis by localization to mitochondria and the formation of a high affinity homo- or heterodimeric complex.

  7. Dimerization of merocyanine dyes. Structural and energetic characterization of dipolar dye aggregates and implications for nonlinear optical materials.

    Science.gov (United States)

    Würthner, Frank; Yao, Sheng; Debaerdemaeker, Tony; Wortmann, Rüdiger

    2002-08-14

    Aggregation of polar merocyanine dyes has been identified as an important problem in the fabrication of organic materials for photonic applications. In this work, a series of merocyanine dyes is synthesized, and their aggregation is investigated by a combination of several experimental techniques to reveal structure-property relationships. These studies provide clear evidence for the formation of centrosymmetric dimers for all investigated merocyanines in concentrated solution and in the solid state. The thermodynamics of dimerization in liquid solution is studied by concentration-dependent permittivity measurements, UV-vis spectroscopy, and electrooptical absorption experiments. A centrosymmetric dimer structure with antiparallel ordering of the dipole moments is observed in solution by 2D NMR spectroscopy as well as in the solid state by X-ray crystallography and interpreted in terms of dipolar and pi-pi interactions. The optical properties of the dimer aggregates are satisfactorily explained by an excitonic coupling model. The effect of an external electric field on the dimerization equilibrium is considered and quantitatively determined by electrooptical absorption measurements. Implications of the observed findings on the design of nonlinear optical and photorefractive materials are discussed.

  8. Acidic Residues Control the Dimerization of the N-terminal Domain of Black Widow Spiders’ Major Ampullate Spidroin 1

    Science.gov (United States)

    Bauer, Joschka; Schaal, Daniel; Eisoldt, Lukas; Schweimer, Kristian; Schwarzinger, Stephan; Scheibel, Thomas

    2016-01-01

    Dragline silk is the most prominent amongst spider silks and comprises two types of major ampullate spidroins (MaSp) differing in their proline content. In the natural spinning process, the conversion of soluble MaSp into a tough fiber is, amongst other factors, triggered by dimerization and conformational switching of their helical amino-terminal domains (NRN). Both processes are induced by protonation of acidic residues upon acidification along the spinning duct. Here, the structure and monomer-dimer-equilibrium of the domain NRN1 of Latrodectus hesperus MaSp1 and variants thereof have been investigated, and the key residues for both could be identified. Changes in ionic composition and strength within the spinning duct enable electrostatic interactions between the acidic and basic pole of two monomers which prearrange into an antiparallel dimer. Upon naturally occurring acidification this dimer is stabilized by protonation of residue E114. A conformational change is independently triggered by protonation of clustered acidic residues (D39, E76, E81). Such step-by-step mechanism allows a controlled spidroin assembly in a pH- and salt sensitive manner, preventing premature aggregation of spider silk proteins in the gland and at the same time ensuring fast and efficient dimer formation and stabilization on demand in the spinning duct. PMID:27681031

  9. HPLC analysis for the clinical-biochemical diagnosis of inborn errors of metabolism of purines and pyrimidines.

    Science.gov (United States)

    Lazzarino, Giuseppe; Amorini, Angela Maria; Di Pietro, Valentina; Tavazzi, Barbara

    2011-01-01

    The determination of purines and pyrimidines in biofluids is useful for the clinical-biochemical characterization of acute and chronic pathological states that induce transient or permanent alterations of metabolism. In particular, the diagnosis of several inborn errors of metabolism (IEMs) is accomplished by the analysis of circulating and excreted purines and pyrimidines. It is certainly advantageous to simultaneously determine the full purine and pyrimidine profile, as well as to quantify other compounds of relevance (e.g., organic acids, amino acids, sugars) in various metabolic hereditary diseases, in order to screen for a large number of IEMs using a reliable and sensitive analytical method characterized by mild to moderate costs. Toward this end, we have developed an ion-pairing HPLC method with diode array detection for the synchronous separation of several purines and pyrimidines. This method also allows the quantification of additional compounds such as N-acetylated amino acids and dicarboxylic acids, the concentrations of which are profoundly altered in different IEMs. The application of the method in the analysis of biological samples from patients with suspected purine and pyrimidine disorders is presented to illustrate its applicability for the clinical-biochemical diagnosis of IEM.

  10. Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Inoue, Masayuki [Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kita, Kiyoshi [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Harada, Shigeharu [Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Tanaka, Akiko [Systems and Structural Biology Center, RIKEN, Tsurumi, Yokohama 230-0045 (Japan); Aoki, Takashi [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nara, Takeshi, E-mail: tnara@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. Black-Right-Pointing-Pointer Disruption of the cpsII gene significantly reduced the growth of epimastigotes. Black-Right-Pointing-Pointer In particular, the CPSII-null mutant severely retarded intracellular growth. Black-Right-Pointing-Pointer The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes-an insect form-possess both activities, amastigotes-an intracellular replicating form of T. cruzi-are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

  11. Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Brahmachari Samir K

    2001-10-01

    Full Text Available Abstract Background Poly purine.pyrimidine sequences have the potential to adopt intramolecular triplex structures and are overrepresented upstream of genes in eukaryotes. These sequences may regulate gene expression by modulating the interaction of transcription factors with DNA sequences upstream of genes. Results A poly purine.pyrimidine sequence with the potential to adopt an intramolecular triplex DNA structure was designed. The sequence was inserted within a nucleosome positioned upstream of the β-galactosidase gene in yeast, Saccharomyces cerevisiae, between the cycl promoter and gal 10Upstream Activating Sequences (UASg. Upon derepression with galactose, β-galactosidase gene expression is reduced 12-fold in cells carrying single copy poly purine.pyrimidine sequences. This reduction in expression is correlated with reduced transcription. Furthermore, we show that plasmids carrying a poly purine.pyrimidine sequence are not specifically lost from yeast cells. Conclusion We propose that a poly purine.pyrimidine sequence upstream of a gene affects transcription. Plasmids carrying this sequence are not specifically lost from cells and thus no additional effort is needed for the replication of these sequences in eukaryotic cells.

  12. Two new Pb coordination polymers derived from pyrimidine-2-thiolate: Synthesis, methyl substitution-induced effect and properties

    Science.gov (United States)

    Song, Jiang-Feng; Li, Si-Zhe; Zhou, Rui-Sha; Hu, Tuo-Ping; Shao, Jia; Zhang, Xiao

    2016-07-01

    Two new coordination compounds, {Pb(pymt)2}∞ (1) and {Pb(mpymt)2}∞ (2) (pymt = pyrimidine-2-thiolate and mpymt = 4-methyl-pyrimidine-2-thione) have been synthesized under solvothermal conditions and characterized by elemental analyses, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction and single-crystal X-ray diffraction. In compounds 1 and 2, pymt- and mpymt- adopt the same coordination modes (μ-1 κN, S and μ2-1 κN, S: 2 κS, N) to interacted with Pb2+, however, different topology structures for compounds 1 and 2 are obtained. Compound 1 displays a one-dimensional (1D) ribbon with square cavity constructed from two double concentric chains of [Pb-S]∞ and [Pb-Pyrimidine] ∞ sharing Pb1 ions. Compound 2 shows 1D polymeric single chain constructed by [Pb-S]∞ and [Pb-methyl-pyrimidine]∞ chains. The results revealed that the methyl groups don't influence the coordination modes of pyrimidine-2-thiolate but directed the structural variations. Moreover, the fluorescent properties of compounds 1 and 2 were investigated.

  13. Exact Solution of a Generalized Nonlinear Schrodinger Equation Dimer

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Maniadis, P.; Tsironis, G.P.

    1998-01-01

    We present exact solutions for a nonlinear dimer system defined throught a discrete nonlinear Schrodinger equation that contains also an integrable Ablowitz-Ladik term. The solutions are obtained throught a transformation that maps the dimer into a double Sine-Gordon like ordinary nonlinear...... differential equation....

  14. Synthesis of novel organo-phosphorus C60 dimers

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Carbon bridged organophosphorus C60 dimers were obtained by the reaction of aminome- thylenebisphosphonate anion with C60 and fully characterized by 1HNMR, 31PNMR, 13CNMR, FT- MALDI-MS, FT-IR, UV-Vis, DEPT and HMBC, and the dimeric compounds undergo hydrolysis by using TMSI.

  15. Local field enhancement: comparing self-similar and dimer nanoantennas

    CERN Document Server

    Pellegrini, Giovanni; Finazzi, Marco; Biagioni, Paolo

    2016-01-01

    We study the local field enhancement properties of self-similar nanolenses and compare the obtained results with the performance of standard dimer nanoantennas. We report that, despite the additional structural complexity, self-similar nanolenses are unable to provide significant improvements over the field enhancement performance of standard plasmonic dimers.

  16. Synthesis,Characterization,and Electrochemical Property of Nanometer Porphyrin Dimer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A nanometer porphyrin dimer was synthesized with fumaryl chloride as a bridge-linked reagent. The characterization was carried out with elemental analyses, 1H NMR, UV-Vis, and IR spectrometries, and then the electrochemical properties of the porphyrins were studied. The authors found that there was moderate electronic communication between the two porphyrin rings in the nanometer porphyrin dimer.

  17. Dimerization process of amyloid-β(29-42) studied by the Hamiltonian replica-permutation molecular dynamics simulations.

    Science.gov (United States)

    Itoh, Satoru G; Okumura, Hisashi

    2014-10-02

    The amyloid-β peptides form amyloid fibrils which are associated with Alzheimer's disease. Amyloid-β(29-42) is its C-terminal fragment and a critical determinant of the amyloid formation rate. This fragment forms the amyloid fibril by itself. However, the fragment conformation in the fibril has yet to be determined. The oligomerization process including the dimerization process is also still unknown. The dimerization process corresponds to an early process of the amyloidogenesis. In order to investigate the dimerization process and conformations, we applied the Hamiltonian replica-permutation method, which is a better alternative to the Hamiltonian replica-exchange method, to two amyloid-β(29-42) molecules in explicit water solvent. At the first step of the dimerization process, two amyloid-β(29-42) molecules came close to each other and had intermolecular side chain contacts. When two molecules had the intermolecular side chain contacts, the amyloid-β(29-42) tended to have intramolecular secondary structures, especially β-hairpin structures. The two molecules had intermolecular β-bridge structures by coming much closer at the second step of the dimerization process. Formation of these intermolecular β-bridge structures was induced by the β-hairpin structures. The intermolecular β-sheet structures elongated at the final step. Structures of the amyloid-β(29-42) in the monomer and dimer states are also shown with the free-energy landscapes, which were obtained by performing efficient sampling in the conformational space in our simulations.

  18. Atomic resolution crystal structure of VcLMWPTP-1 from Vibrio cholerae O395: Insights into a novel mode of dimerization in the low molecular weight protein tyrosine phosphatase family

    Energy Technology Data Exchange (ETDEWEB)

    Nath, Seema; Banerjee, Ramanuj; Sen, Udayaditya, E-mail: udayaditya.sen@saha.ac.in

    2014-07-18

    Highlights: • VcLMWPTP-1 forms dimer in solution. • The dimer is catalytically active unlike other reported dimeric LMWPTPs. • The formation of extended dimeric surface excludes the active site pocket. • The surface bears closer resemblance to eukaryotic LMWPTPs. - Abstract: Low molecular weight protein tyrosine phosphatase (LMWPTP) is a group of phosphotyrosine phosphatase ubiquitously found in a wide range of organisms ranging from bacteria to mammals. Dimerization in the LMWPTP family has been reported earlier which follows a common mechanism involving active site residues leading to an enzymatically inactive species. Here we report a novel form of dimerization in a LMWPTP from Vibrio cholera 0395 (VcLMWPTP-1). Studies in solution reveal the existence of the dimer in solution while kinetic study depicts the active form of the enzyme. This indicates that the mode of dimerization in VcLMWPTP-1 is different from others where active site residues are not involved in the process. A high resolution (1.45 Å) crystal structure of VcLMWPTP-1 confirms a different mode of dimerization where the active site is catalytically accessible as evident by a tightly bound substrate mimicking ligand, MOPS at the active site pocket. Although being a member of a prokaryotic protein family, VcLMWPTP-1 structure resembles very closely to LMWPTP from a eukaryote, Entamoeba histolytica. It also delineates the diverse surface properties around the active site of the enzyme.

  19. Loop groups, Clusters, Dimers and Integrable systems

    CERN Document Server

    Fock, V V

    2014-01-01

    We describe a class of integrable systems on Poisson submanifolds of the affine Poisson-Lie groups $\\widehat{PGL}(N)$, which can be enumerated by cyclically irreducible elements the co-extended affine Weyl groups $(\\widehat{W}\\times \\widehat{W})^\\sharp$. Their phase spaces admit cluster coordinates, whereas the integrals of motion are cluster functions. We show, that this class of integrable systems coincides with the constructed by Goncharov and Kenyon out of dimer models on a two-dimensional torus and classified by the Newton polygons. We construct the correspondence between the Weyl group elements and polygons, demonstrating that each particular integrable model admits infinitely many realisations on the Poisson-Lie groups. We also discuss the particular examples, including the relativistic Toda chains and the Schwartz-Ovsienko-Tabachnikov pentagram map.

  20. Pseudo-two-dimensional random dimer lattices

    Energy Technology Data Exchange (ETDEWEB)

    Naether, U., E-mail: naether@unizar.es [Instituto de Ciencia de Materiales de Aragón and Departamento de Física de la Materia Condensada, CSIC – Universidad de Zaragoza, 50009 Zaragoza (Spain); Mejía-Cortés, C.; Vicencio, R.A. [Departamento de Física and MSI – Nucleus for Advanced Optics, Center for Optics and Photonics (CEFOP), Facultad de Ciencias, Universidad de Chile, Santiago (Chile)

    2015-06-05

    We study the long-time wave transport in correlated and uncorrelated disordered 2D arrays. When a separation of dimensions is applied to the model, we find that the previously predicted 1D random dimer phenomenology also appears in so-called pseudo-2D arrays. Therefore, a threshold behavior is observed in terms of the effective size for eigenmodes, as well as in long-time dynamics. A minimum system size is required to observe this threshold, which is very important when considering a possible experimental realization. For the long-time evolution, we find that for correlated lattices a super-diffusive long-range transport is observed. For completely uncorrelated disorder 2D transport becomes sub-diffusive within the localization length and for random binary pseudo-2D arrays localization is observed.