WorldWideScience

Sample records for 14-residue fibrillogenic peptide

  1. Optimized co-solute paramagnetic relaxation enhancement for the rapid NMR analysis of a highly fibrillogenic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Oktaviani, Nur Alia [University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute (Netherlands); Risør, Michael W. [University of Aarhus, Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry (Denmark); Lee, Young-Ho [Osaka University, Institute for Protein Research (Japan); Megens, Rik P. [University of Groningen, Stratingh Institute for Chemistry (Netherlands); Jong, Djurre H. de; Otten, Renee; Scheek, Ruud M. [University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute (Netherlands); Enghild, Jan J. [University of Aarhus, Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics (Denmark); Nielsen, Niels Chr. [University of Aarhus, Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry (Denmark); Ikegami, Takahisa [Yokohama City University, Graduate School of Medical Life Science (Japan); Mulder, Frans A. A., E-mail: fmulder@chem.au.dk [University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute (Netherlands)

    2015-06-15

    Co-solute paramagnetic relaxation enhancement (PRE) is an attractive way to speed up data acquisition in NMR spectroscopy by shortening the T{sub 1} relaxation time of the nucleus of interest and thus the necessary recycle delay. Here, we present the rationale to utilize high-spin iron(III) as the optimal transition metal for this purpose and characterize the properties of its neutral chelate form Fe(DO3A) as a suitable PRE agent. Fe(DO3A) effectively reduces the T{sub 1} values across the entire sequence of the intrinsically disordered protein α-synuclein with negligible impact on line width. The agent is better suited than currently used alternatives, shows no specific interaction with the polypeptide chain and, due to its high relaxivity, is effective at low concentrations and in ‘proton-less’ NMR experiments. By using Fe(DO3A) we were able to complete the backbone resonance assignment of a highly fibrillogenic peptide from α{sub 1}-antitrypsin by acquiring the necessary suite of multidimensional NMR datasets in 3 h.

  2. Optimized co-solute paramagnetic relaxation enhancement for the rapid NMR analysis of a highly fibrillogenic peptide

    International Nuclear Information System (INIS)

    Co-solute paramagnetic relaxation enhancement (PRE) is an attractive way to speed up data acquisition in NMR spectroscopy by shortening the T1 relaxation time of the nucleus of interest and thus the necessary recycle delay. Here, we present the rationale to utilize high-spin iron(III) as the optimal transition metal for this purpose and characterize the properties of its neutral chelate form Fe(DO3A) as a suitable PRE agent. Fe(DO3A) effectively reduces the T1 values across the entire sequence of the intrinsically disordered protein α-synuclein with negligible impact on line width. The agent is better suited than currently used alternatives, shows no specific interaction with the polypeptide chain and, due to its high relaxivity, is effective at low concentrations and in ‘proton-less’ NMR experiments. By using Fe(DO3A) we were able to complete the backbone resonance assignment of a highly fibrillogenic peptide from α1-antitrypsin by acquiring the necessary suite of multidimensional NMR datasets in 3 h

  3. Amylin under examination. Fibrillogenic polypeptide hormone of the pancreas

    Directory of Open Access Journals (Sweden)

    Małgorzata Marszałek

    2014-01-01

    Full Text Available In patients or animals affected by type 2 diabetes mellitus (DM2, non-insulin dependent diabetes mellitus [NIDDM] some pathological deposits, called amyloid, are observed among cells of islets of Langerhans. Among other constituents, deposits consist of an insoluble, fibrillar form of peptide neurohormone called amylin, produced by pancreatic beta cells. It is thought that formation of fibrillar deposits of misfolded and aggregated peptide is highly toxic to beta cells and leads to cell dysfunction, cell loss, pancreas destruction and progress of the disease. This relatively small 37-amino acid peptide constitutes a serious scientific, research and to some extent a medical problem. This article presents amylin as a hormone, neurohormone and as a fibrillating molecule which participates in amyloid deposit formation in human and animal pancreas. The role of some amino acids important for fibril formation has been highlighted.

  4. Oxpholipin 11D: An Anti-Inflammatory Peptide That Binds Cholesterol and Oxidized Phospholipids

    OpenAIRE

    Piotr Ruchala; Mohamad Navab; Chun-Ling Jung; Susan Hama-Levy; Micewicz, Ewa D.; Hai Luong; Reyles, Jonathan E.; Shantanu Sharma; Waring, Alan J.; Fogelman, Alan M.; Lehrer, Robert I.

    2010-01-01

    BACKGROUND: Many gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. METHODOLOGY/RESULTS: Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemot...

  5. From peptide precursors to oxazole and thiazole-containing peptide antibiotics: microcin B17 synthase.

    Science.gov (United States)

    Li, Y M; Milne, J C; Madison, L L; Kolter, R; Walsh, C T

    1996-11-15

    Esherichia coli microcin B17 is a posttranslationally modified peptide that inhibits bacterial DNA gyrase. It contains four oxazole and four thiazole rings and is representative of a broad class of pharmaceutically important natural products with five-membered heterocycles derived from peptide precursors. An in vitro assay was developed to detect heterocycle formation, and an enzyme complex, microcin B17 synthase, was purified and found to contain three proteins, McbB, McbC, and McbD, that convert 14 residues into the eight mono- and bisheterocyclic moieties in vitro that confer antibiotic activity on mature microcin B17. These enzymatic reactions alter the peptide backbone connectivity. The propeptide region of premicrocin is the major recognition determinant for binding and downstream heterocycle formation by microcin B17 synthase. A general pathway for the enzymatic biosynthesis of these heterocycles is formulated.

  6. The production of Multiple Small Peptaibol Families by Single 14-Module Peptide Synthetases in Trichoderma/Hypocrea

    Energy Technology Data Exchange (ETDEWEB)

    Degenkolb, Thomas; Aghchehb, Razieh Karimi; Dieckmann, Ralf; Neuhof, Torsten; Baker, Scott E.; Druzhinina, Irina S.; Kubicek, Christian P.; Brückner, Hans; von Dohren, Hans

    2012-03-01

    The most common peptaibibiotic structures are 11-residue peptaibols found widely distributed in the genus Trichoderma/Hypocrea. Frequently associated are 14-residue peptaibols sharing partial sequence identity. Genome sequencing projects of 3 Trichoderma strains of the major clades reveal the presence of up to 3 types of nonribosomal peptide synthetases with 7, 14, or 18-20 amino acid adding modules. We here provide evidence that the 14-module NRPS type found in T. virens, T. reesei (teleomorph Hypocrea jecorina) and T. atroviride produces both 11- and 14- residue peptaibols based on the disruption of the respective NRPS gene of T. reesei, and bioinformatic analysis of their amino acid activating domains and modules. The structures of these peptides may be predicted from the gene structures and have been confirmed by analysis of families of 11- and 14-residue peptaibols from the strain 618, termed hypojecorins A (23 sequences determined, 4 new) and B (3 new sequences), and the recently established trichovirins A from T. virens. The distribution of 11- and 14-residue products is strain-specific and depends on growth conditions as well. Possible mechanisms of module skipping are discussed.

  7. Oxpholipin 11D: an anti-inflammatory peptide that binds cholesterol and oxidized phospholipids.

    Directory of Open Access Journals (Sweden)

    Piotr Ruchala

    Full Text Available BACKGROUND: Many gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. METHODOLOGY/RESULTS: Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D, contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospholipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable alpha-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. CONCLUSION: Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential.

  8. Antimicrobial peptides.

    Science.gov (United States)

    Zhang, Ling-Juan; Gallo, Richard L

    2016-01-11

    Antimicrobial peptides and proteins (AMPs) are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multicellular organisms. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, viruses and even cancer cells. Insects and plants primarily deploy AMPs as an antibiotic to protect against potential pathogenic microbes, but microbes also produce AMPs to defend their environmental niche. In higher eukaryotic organisms, AMPs can also be referred to as 'host defense peptides', emphasizing their additional immunomodulatory activities. These activities are diverse, specific to the type of AMP, and include a variety of cytokine and growth factor-like effects that are relevant to normal immune homeostasis. In some instances, the inappropriate expression of AMPs can also induce autoimmune diseases, thus further highlighting the importance of understanding these molecules and their complex activities. This Primer will provide an update of our current understanding of AMPs. PMID:26766224

  9. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

  10. Peptides derived from CXCL8 based on in silico analysis inhibit CXCL8 interactions with its receptor CXCR1

    Science.gov (United States)

    Jiang, Shinn-Jong; Liou, Je-Wen; Chang, Chun-Chun; Chung, Yi; Lin, Lee-Fong; Hsu, Hao-Jen

    2015-12-01

    Chemokine CXCL8 is crucial for regulation of inflammatory and immune responses via activating its cognate receptor CXCR1. In this study, molecular docking and binding free energy calculations were combined to predict the initial binding event of CXCL8 to CXCR1 for peptide drug design. The simulations reveal that in the initial binding, the N-loop of CXCL8 interacts with the N-terminus of CXCR1, which is dominated by electrostatic interactions. The derived peptides from the binding region of CXCL8 are synthesized for further confirmation. Surface plasmon resonance analyses indicate that the CXCL8 derived peptide with 14 residues is able to bind to the receptor CXCR1 derived peptide with equilibrium KD of 252 μM while the peptide encompassing a CXCL8 K15A mutation hardly binds to CXCR1 derived peptide (KD = 1553 μM). The cell experiments show that the designed peptide inhibits CXCL8-induced and LPS-activated monocytes adhesion and transmigration. However, when the peptides were mutated on two lysine residues (K15 and K20), the inhibition effects were greatly reduced indicating these two amino acids are key residues for the initial binding of CXCL8 to CXCR1. This study demonstrates that in silico prediction based functional peptide design can be effective for developing anti-inflammation drugs.

  11. Design and characterization of short antimicrobial peptides using leucine zipper templates with selectivity towards microorganisms.

    Science.gov (United States)

    Ahmad, Aqeel; Azmi, Sarfuddin; Srivastava, Saurabh; Kumar, Amit; Tripathi, Jitendra Kumar; Mishra, Nripendra N; Shukla, Praveen K; Ghosh, Jimut Kanti

    2014-11-01

    Design of antimicrobial peptides with selective activity towards microorganisms is an important step towards the development of new antimicrobial agents. Leucine zipper sequence has been implicated in cytotoxic activity of naturally occurring antimicrobial peptides; moreover, this motif has been utilized for the design of novel antimicrobial peptides with modulated cytotoxicity. To understand further the impact of substitution of amino acids at 'a' and/or 'd' position of a leucine zipper sequence of an antimicrobial peptides on its antimicrobial and cytotoxic properties four short peptides (14-residue) were designed on the basis of a leucine zipper sequence without or with replacement of leucine residues in its 'a' and 'd' positions with D-leucine or alanine or proline residue. The original short leucine zipper peptide (SLZP) and its D-leucine substituted analog, DLSA showed comparable activity against the tested Gram-positive and negative bacteria and the fungal strains. The alanine substituted analog (ASA) though showed appreciable activity against the tested bacteria, it showed to some extent lower activity against the tested fungi. However, the proline substituted analog (PSA) showed lower activity against the tested bacterial or fungal strains. Interestingly, DLSA, ASA and PSA showed significantly lower cytotoxicity than SLZP against both human red blood cells (hRBCs) and murine 3T3 cells. Cytotoxic and bactericidal properties of these peptides matched with peptide-induced damage/permeabilization of mammalian cells and bacteria or their mimetic lipid vesicles suggesting cell membrane could be the target of these peptides. As evidenced by tryptophan fluorescence and acrylamide quenching studies the peptides showed similarities either in interaction or in their localization within the bacterial membrane mimetic negatively charged lipid vesicles. Only SLZP showed localization inside the mammalian membrane mimetic zwitterionic lipid vesicles. The results show

  12. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

  13. Self-assembly and sequence length dependence on nanofibrils of polyglutamine peptides.

    Science.gov (United States)

    Inayathullah, Mohammed; Tan, Aaron; Jeyaraj, Rebecca; Lam, James; Cho, Nam-Joon; Liu, Corey W; Manoukian, Martin A C; Ashkan, Keyoumars; Mahmoudi, Morteza; Rajadas, Jayakumar

    2016-06-01

    Huntington's disease (HD) is recognized as a currently incurable, inherited neurodegenerative disorder caused by the accumulation of misfolded polyglutamine (polyQ) peptide aggregates in neuronal cells. Yet, the mechanism by which newly formed polyQ chains interact and assemble into toxic oligomeric structures remains a critical, unresolved issue. In order to shed further light on the matter, our group elected to investigate the folding of polyQ peptides - examining glutamine repeat lengths ranging from 3 to 44 residues. To characterize these aggregates we employed a diverse array of technologies, including: nuclear magnetic resonance; circular dichroism; Fourier transform infrared spectroscopy; fluorescence resonance energy transfer (FRET), and atomic force microscopy. The data we obtained suggest that an increase in the number of glutamine repeats above 14 residues results in disordered loop structures, with different repeat lengths demonstrating unique folding characteristics. This differential folding manifests in the formation of distinct nano-sized fibrils, and on this basis, we postulate the idea of 14 polyQ repeats representing a critical loop length for neurotoxicity - a property that we hope may prove amenable to future therapeutic intervention. Furthermore, FRET measurements on aged assemblages indicate an increase in the end-to-end distance of the peptide with time, most probably due to the intermixing of individual peptide strands within the nanofibril. Further insight into this apparent time-dependent reorganization of aggregated polyQ peptides may influence future disease modeling of polyQ-related proteinopathies, in addition to directing novel clinical innovations. PMID:26874369

  14. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  15. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  16. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  17. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  18. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  19. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  20. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  1. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  2. Plant signalling peptides

    OpenAIRE

    Wiśniewska, Justyna; Trejgell, Alina; Tretyn, Andrzej

    2003-01-01

    Biochemical and genetic studies have identified peptides that play crucial roles in plant growth and development, including defence mechanisms in response to wounding by pests, the control of cell division and expansion, and pollen self-incompatibility. The first two signalling peptides to be described in plants were tomato systemin and phytosulfokine (PSK). There is also biochemical evidence that natriuretic peptide-like molecules, immunologically-relatedt o those found ...

  3. Polycyclic peptide therapeutics.

    Science.gov (United States)

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

  4. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  5. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  6. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  7. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  8. Introduction to Peptide Synthesis

    OpenAIRE

    Stawikowski, Maciej; Fields, Gregg B.

    2002-01-01

    A number of synthetic peptides are significant commercial or pharmaceutical products, ranging from the dipeptide sugar-substitute aspartame to clinically used hormones, such as oxytocin, adrenocorticotropic hormone, and calcitonin. This unit provides an overview of the field of synthetic peptides and proteins. It discusses selecting the solid support and common coupling reagents. Additional information is provided regarding common side reactions and synthesizing modified residues.

  9. Antimicrobial Peptides from Plants

    Science.gov (United States)

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  10. Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    James P. Tam

    2015-11-01

    Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.

  11. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  12. Electromembrane extraction of peptides.

    Science.gov (United States)

    Balchen, Marte; Reubsaet, Léon; Pedersen-Bjergaard, Stig

    2008-06-20

    Rapid extraction of eight different peptides using electromembrane extraction (EME) was demonstrated for the first time. During an extraction time of 5 min, the model peptides migrated from a 500 microL aqueous acidic sample solution, through a thin supported liquid membrane (SLM) of an organic liquid sustained in the pores in the wall of a porous hollow fiber, and into a 25 microL aqueous acidic acceptor solution present inside the lumen of the hollow fiber. The driving force of the extraction was a 50 V potential sustained across the SLM, with the positive electrode in the sample and the negative electrode in the acceptor solution. The nature and the composition of the SLM were highly important for the EME process, and a mixture of 1-octanol and 15% di(2-ethylhexyl) phosphate was found to work properly. Using 1mM HCl as background electrolyte in the sample and 100 mM HCl in the acceptor solution, and agitation at 1050 rpm, enrichment up to 11 times was achieved. Recoveries were found to be dependent on the structure of the peptide, indicating that the polarity and the number of ionized groups were important parameters affecting the extraction efficiency. The experimental findings suggested that electromembrane extraction of peptides is possible and may be a valuable tool for future extraction of peptides. PMID:18479691

  13. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity......Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... and hence adjuvants are included to enhance and direct the immune response. Although the vaccine has been tested in ART naïve individuals, we recommend future testing of the vaccine during (early started) ART that improves immune function and to select individuals likely to benefit. Peptides representing...

  14. Synthetic antibiofilm peptides.

    Science.gov (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. PMID:26724202

  15. Biomimetic peptide nanosensors.

    Science.gov (United States)

    Cui, Yue; Kim, Sang N; Naik, Rajesh R; McAlpine, Michael C

    2012-05-15

    The development of a miniaturized sensing platform tailored for sensitive and selective detection of a variety of biochemical analytes could offer transformative fundamental and technological opportunities. Due to their high surface-to-volume ratios, nanoscale materials are extremely sensitive sensors. Likewise, peptides represent robust substrates for selective recognition due to the potential for broad chemical diversity within their relatively compact size. Here we explore the possibilities of linking peptides to nanosensors for the selective detection of biochemical targets. Such systems raise a number of interesting fundamental challenges: What are the peptide sequences, and how can rational design be used to derive selective binders? What nanomaterials should be used, and what are some strategies for assembling hybrid nanosensors? What role does molecular modeling play in elucidating response mechanisms? What is the resulting performance of these sensors, in terms of sensitivity, selectivity, and response time? What are some potential applications? This Account will highlight our early attempts to address these research challenges. Specifically, we use natural peptide sequences or sequences identified from phage display as capture elements. The sensors are based on a variety of nanomaterials including nanowires, graphene, and carbon nanotubes. We couple peptides to the nanomaterial surfaces via traditional surface functionalization methods or self-assembly. Molecular modeling provides detailed insights into the hybrid nanostructure, as well as the sensor detection mechanisms. The peptide nanosensors can distinguish chemically camouflaged mixtures of vapors and detect chemical warfare agents with sensitivities as low as parts-per-billion levels. Finally, we anticipate future uses of this technology in biomedicine: for example, devices based on these sensors could detect disease from the molecular components in human breath. Overall, these results provide a

  16. Dicyclopropylmethyl peptide backbone protectant.

    Science.gov (United States)

    Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-08-20

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106-126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit.

  17. Invertebrate FMRFamide related peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2013-06-01

    In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been isolated from invertebrate animals. Precursors to the FaRPs likely arose in the cnidarians. With the transition to a bilateral body plan FaRPs became a fixture in the invertebrate phyla. They have come to play a critical role as neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety of body functions including, feeding, digestion, circulation, reproduction, movement. The evolution of the molecular form and function of these omnipresent peptides will be considered.

  18. Natriuretic peptides and cerebral hemodynamics

    DEFF Research Database (Denmark)

    Guo, Song; Barringer, Filippa; Zois, Nora Elisabeth;

    2014-01-01

    Natriuretic peptides have emerged as important diagnostic and prognostic tools for cardiovascular disease. Plasma measurement of the bioactive peptides as well as precursor-derived fragments is a sensitive tool in assessing heart failure. In heart failure, the peptides are used as treatment...

  19. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class of ...

  20. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  1. Biochemical functionalization of peptide nanotubes with phage displayed peptides.

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering. PMID:27479451

  2. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  3. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  4. Antimicrobial peptides in Echinoderms

    Directory of Open Access Journals (Sweden)

    C Li

    2010-05-01

    Full Text Available Antimicrobial peptides (AMPs are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, dissimilar to other known AMPs. A family of heterodimeric AMPs, named centrocins, are also present in S. droebachiensis. Lysozymes and fragments of larger proteins, such as beta-thymocins, actin, histone 2A and filamin A have also been shown to display antimicrobial activities in echinoderms. Future studies on AMPs should be aimed in revealing how echinoderms use these AMPs in the immune response against microbial pathogens.

  5. The PeptideAtlas Project

    OpenAIRE

    Deutsch, Eric W.

    2010-01-01

    PeptideAtlas is a multi-species compendium of peptides observed with tandem mass spectrometry methods. Raw mass spectrometer output files are collected from the community and reprocessed through a uniform analysis and validation pipeline that continues to advance. The results are loaded into a database and the information derived from the raw data is returned to the community via several web-based data exploration tools. The PeptideAtlas resource is useful for experiment planning, improving g...

  6. Human Antimicrobial Peptides and Proteins

    OpenAIRE

    Guangshun Wang

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified ...

  7. Peptides that influence membrane topology

    Science.gov (United States)

    Wong, Gerard C. L.

    2014-03-01

    We examine the mechanism of a range of polypeptides that influence membrane topology, including antimicrobial peptides, cell penetrating peptides, viral fusion peptides, and apoptosis proteins, and show how a combination of geometry, coordination chemistry, and soft matter physics can be used to approach a unified understanding. We will also show how such peptides can impact biomedical problems such as auto-immune diseases (psoriasis, lupus), infectious diseases (viral and bacterial infections), and mitochondrial pathologies (under-regulated apoptosis leads to neurodegenerative diseases whereas over-regulated apoptosis leads to cancer.)

  8. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor...... and heparan sulfate proteoglycans (HSPG) have been identified. The FGL, dekaCAM, FRM/EncaminA, BCL, EncaminC and EncaminE peptides all target the FGF receptor whereas the heparin binding peptide HBP targets HSPG. Moreover, a number of NCAM binding peptides have been identified employing screening...

  9. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology. PMID:26279082

  10. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  11. Biodiscovery of aluminum binding peptides

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

    2013-05-01

    Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

  12. Polyclonal Peptide Antisera.

    Science.gov (United States)

    Pihl, Tina H; Illigen, Kristin E; Houen, Gunnar

    2015-01-01

    Polyclonal antibodies are relatively easy to produce and may supplement monoclonal antibodies for some applications or even have some advantages. The choice of species for production of (peptide) antisera is based on practical considerations, including availability of immunogen (vaccine) and animals. Two major factors govern the production of antisera: the nature of adaptive immune responses, which take place over days/weeks and ethical guidelines for animal welfare. Here, simple procedures for immunization of mice, rabbits, sheep, goats, pigs, horses, and chickens are presented. PMID:26424267

  13. Radiolabelled peptides for oncological diagnosis.

    NARCIS (Netherlands)

    Laverman, P.; Sosabowski, J.K.; Boerman, O.C.; Oyen, W.J.G.

    2012-01-01

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of resea

  14. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  15. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptide...

  16. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  17. Conus venom peptide pharmacology.

    Science.gov (United States)

    Lewis, Richard J; Dutertre, Sébastien; Vetter, Irina; Christie, MacDonald J

    2012-04-01

    Conopeptides are a diverse group of recently evolved venom peptides used for prey capture and/or defense. Each species of cone snails produces in excess of 1000 conopeptides, with those pharmacologically characterized (≈ 0.1%) targeting a diverse range of membrane proteins typically with high potency and specificity. The majority of conopeptides inhibit voltage- or ligand-gated ion channels, providing valuable research tools for the dissection of the role played by specific ion channels in excitable cells. It is noteworthy that many of these targets are found to be expressed in pain pathways, with several conopeptides having entered the clinic as potential treatments for pain [e.g., pyroglutamate1-MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain [ziconotide (Prialt)]. This review discusses the diversity, pharmacology, structure-activity relationships, and therapeutic potential of cone snail venom peptide families acting at voltage-gated ion channels (ω-, μ-, μO-, δ-, ι-, and κ-conotoxins), ligand-gated ion channels (α-conotoxins, σ-conotoxin, ikot-ikot, and conantokins), G-protein-coupled receptors (ρ-conopeptides, conopressins, and contulakins), and neurotransmitter transporters (χ-conopeptides), with expanded discussion on the clinical potential of sodium and calcium channel inhibitors and α-conotoxins. Expanding the discovery of new bioactives using proteomic/transcriptomic approaches combined with high-throughput platforms and better defining conopeptide structure-activity relationships using relevant membrane protein crystal structures are expected to grow the already significant impact conopeptides have had as both research probes and leads to new therapies. PMID:22407615

  18. Potential of phage-displayed peptide library technology to identify functional targeting peptides

    Science.gov (United States)

    Krumpe, Lauren RH; Mori, Toshiyuki

    2010-01-01

    Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. PMID:20150977

  19. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  20. Peptide primary messengers in plants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The peptide primary messengers regulate embryonic development,cell growth and many other activities in animal cells. But recent evidence verified that peptide primary messengers are also involved in plant defense responses, the recognition between pollen and stigma and keep the balance between cell proliferation and differentiations in shoot apical meristems. Those results suggest that plants may actually make wide use of peptide primary messengers, both in embryonic development and late life when they rally their cells to defend against pathogens and insect pests. The recent advance in those aspects is reviewed.

  1. Screening of TACE Peptide Inhibitors from Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To obtain the recombinant tumor necrosis factor-α converting enzyme (TACE) ectodomain and use it as a selective molecule for the screening of TACE peptide inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain (T1300) of TACE were amplified by RTPCR, and the expression plasmids were constructed by inserting T800 and T1300 into plasmid pET28a and pET-28c respectively. The recombinant T800 and T1300 were induced by IPTG, and SDSPAGE and Western blotting analysis results revealed that T800 and T1300 were highly expressed in the form of inclusion body. After Ni2+-NTA resin affinity chromatography, the recombinant proteins were used in the screening of TACE-binding peptides from phage display peptide library respectively. After 4 rounds of biopanning, the positive phage clones were analyzed by ELISA, competitive inhibition assay and DNA sequencing. A common amino acid sequence (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit the TNF-α release from LPS-stimulated human peripheral blood mononuclear cells (PBMC) up to 60.3 %. FACS analysis revealed that the peptide mediated the accumulation of TNF-α on the cell surface. These results demonstrate that the TACE-binding peptide is an effective antagonist of TACE.

  2. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming;

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...

  3. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte;

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...... improve biomolecular recognition by synthetic nucleic acid analogues. Circular dichroism (CD) measurements showed no distortion of the duplex structure by the incorporated peptide chains while studies in human serum indicated superior stability of the POCs compared to LNA/DNA mixmers and unmodified DNA...

  4. Peptide nanostructures in biomedical technology.

    Science.gov (United States)

    Feyzizarnagh, Hamid; Yoon, Do-Young; Goltz, Mark; Kim, Dong-Shik

    2016-09-01

    Nanostructures of peptides have been investigated for biomedical applications due to their unique mechanical and electrical properties in addition to their excellent biocompatibility. Peptides may form fibrils, spheres and tubes in nanoscale depending on the formation conditions. These peptide nanostructures can be used in electrical, medical, dental, and environmental applications. Applications of these nanostructures include, but are not limited to, electronic devices, biosensing, medical imaging and diagnosis, drug delivery, tissue engineering and stem cell research. This review offers a discussion of basic synthesis methods, properties and application of these nanomaterials. The review concludes with recommendations and future directions for peptide nanostructures. WIREs Nanomed Nanobiotechnol 2016, 8:730-743. doi: 10.1002/wnan.1393 For further resources related to this article, please visit the WIREs website. PMID:26846352

  5. Targeting cancer with peptide aptamers

    OpenAIRE

    Seigneuric, Renaud; Gobbo, Jessica; Colas, Pierre; Garrido, Carmen

    2011-01-01

    A major endeavour in cancer chemotherapy is to develop agents that specifically target a biomolecule of interest. There are two main classes of targeting agents: small molecules and biologics. Among biologics (e.g.: antibodies), DNA, RNA but also peptide aptamers are relatively recent agents. Peptide aptamers are seldom described but represent attractive agents that can inhibit a growing panel of oncotargets including Heat Shock Proteins. Potential pitfalls and coming challenges towards succe...

  6. Peptides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bachovchin, W.W.; Unkefer, C.J.

    1994-12-01

    Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.

  7. Kinins and peptide receptors.

    Science.gov (United States)

    Regoli, Domenico; Gobeil, Fernand

    2016-04-01

    This paper is divided into two sections: the first contains the essential elements of the opening lecture presented by Pr. Regoli to the 2015 International Kinin Symposium in S. Paulo, Brazil on June 28th and the second is the celebration of Dr. Regoli's 60 years of research on vasoactive peptides. The cardiovascular homeostasis derives from a balance of two systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS). The biologically active effector entity of RAS is angiotensin receptor-1 (AT-1R), and that of KKS is bradykinin B2 receptor (B2R). The first mediates vasoconstriction, the second is the most potent and efficient vasodilator. Thanks to its complex and multi-functional mechanism of action, involving nitric oxide (NO), prostacyclin and endothelial hyperpolarizing factor (EDHF). B2R is instrumental for the supply of blood, oxygen and nutrition to tissues. KKS is present on the vascular endothelium and functions as an autacoid playing major roles in cardiovascular diseases (CVDs) and diabetes. KKS exerts a paramount role in the prevention of thrombosis and atherosclerosis. Such knowledge emphasizes the already prominent value of the ACE-inhibitors (ACEIs) for the treatment of CVDs and diabetes. Indeed, the ACEIs, thanks to their double action (block of the RAS and potentiation of the KKS) are the ideal agents for a rational treatment of these diseases. PMID:26408609

  8. Antimicrobial peptides in annelids

    Directory of Open Access Journals (Sweden)

    A Tasiemski

    2008-06-01

    Full Text Available Gene encoded antimicrobial peptides (AMPs are widely distributed among living organisms including plants, invertebrates and vertebrates. They constitute important effectors of the innate immune response by exerting multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis and immune induction. In invertebrates, most of the data describe the characterization and/or the function of AMPs in the numerically and economically most representative group which are arthropods. Annelids are among the first coelomates and are therefore of special phylogenetic interest. Compared to other invertebrate groups, data on annelid’s immunity reveal heavier emphasis on the cellular than on the humoral response suggesting that immune defense of annelids seems to be principally developed as cellular immunity.This paper gives an overview of the variety of AMPs identified in the three classes of annelids, i.e. polychaetes, oligochaetes and achaetes. Their functions, when they have been studied, in the humoral or cellular response of annelids are also mentioned.

  9. Antimicrobial peptides in crustaceans

    Directory of Open Access Journals (Sweden)

    RD Rosa

    2010-11-01

    Full Text Available Crustaceans are a large and diverse invertebrate animal group that mounts a complex and efficient innate immune response against a variety of microorganisms. The crustacean immune system is primarily related to cellular responses and the production and release of important immune effectors into the hemolymph. Antimicrobial proteins and/or peptides (AMPs are key components of innate immunity and are widespread in nature, from bacteria to vertebrate animals. In crustaceans, 15 distinct AMP families are currently recognized, although the great majority (14 families comes from members of the order Decapoda. Crustacean AMPs are generally cationic, gene-encoded molecules that are mainly produced by circulating immune-competent cells (hemocytes or are derived from unrelated proteins primarily involved in other biological functions. In this review, we tentatively classified the crustacean AMPs into four main groups based on their amino acid composition, structural features and multi-functionality. We also attempted to summarize the current knowledge on their implication both in an efficient response to microbial infections and in crustacean survival.

  10. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  11. Collagen-like antimicrobial peptides.

    Science.gov (United States)

    Masuda, Ryo; Kudo, Masakazu; Dazai, Yui; Mima, Takehiko; Koide, Takaki

    2016-11-01

    Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016. PMID:27271210

  12. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  13. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  14. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  15. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  16. Exploration of the Medicinal Peptide Space.

    Science.gov (United States)

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs. PMID:26876881

  17. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  18. Recent development of peptide self-assembly

    Institute of Scientific and Technical Information of China (English)

    Xiubo Zhao; Fang Pan; Jian R. Lu

    2008-01-01

    Amino acids are the building blocks to build peptides and proteins. Recent development in peptide synthesis has however enabled us to mimic this natural process by preparing various long and short peptides possessing different conformations and biological functions. The self-assembly of short designed peptides into molecular nanostructures is becoming a growing interest in nanobiotechnology. Self-assembled peptides exhibit several attractive features for applications in tissue regeneration, drug delivery, biological surface engineering as well as in food science, cosmetic industry and antibiotics. The aim of this review is to introduce the readers to a number of representative studies on peptide self-assembly.

  19. Structural characterization of the model amphipathic peptide Ac-LKKLLKLLKKLLKL-NH2 in aqueous solution and with 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoroisopropanol

    Energy Technology Data Exchange (ETDEWEB)

    Buchko, Garry W.; Jain, Avijita; Reback, Matthew L.; Shaw, Wendy J.

    2013-06-03

    Short-chain amphiphilic peptides are promising components in the new generation of engineered biomaterials with many potential applications. The 14-residue leucine-lysine peptide Ac-LKKLLKLLKKLLKL-NH2 (LKα) is one such amphiphilic peptide. The periodic distribution of hydrophobic and hydrophilic amino acid residues in the sequence of LKα has been shown to promote α-helix formation in an ionic environment and at high peptide concentrations (> ~0.5 mM, no salt). Here, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy is used to demonstrate that LKα, in the absence of salt and at concentrations < 0.5 mM, readily adopts a helical structure in the presence of the structure stabilizing agents 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Maximal helical character, as monitored by negative bands with double minima at 222 and 208-210 nm in the CD spectrum, was observed in 20% TFE and 10% HFIP (volume percent). The helical character suggested by the CD data was corroborated with amide to alpha proton, long range, 1HN(i) to 1Hα(i-3) NOEs characteristic of an α-helical structure. In unbuffered water in the absence of a flouronated alcohol and at low peptide concentrations, LKα was essentially unstructured in solution. These observations confirm that LKα has a predisposition to adopt a helical structure that may be maximized with minimal amounts of fluorinated alcohol. This characterization of the structural and physical properties of LKα will assist the design of future biomaterials containing amphiphilic peptides.

  20. Antiviral active peptide from oyster

    Science.gov (United States)

    Zeng, Mingyong; Cui, Wenxuan; Zhao, Yuanhui; Liu, Zunying; Dong, Shiyuan; Guo, Yao

    2008-08-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster ( Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10 5 kDa, 5 1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10 5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  1. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  2. Radioactive labelling of peptidic hormones

    International Nuclear Information System (INIS)

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  3. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    is considered poor compared to medicines for lifestyle diseases. According to the WHO we could be moving towards a post-antibiotic era in which previously treatable infections become fatal. Of special importance are multidrug resistant bacteria from the ESKAPE group (Enterococcus faecium, Staphylococcus aureus...... a cecropin-mellitin hybrid peptide and proved effective in killing colistin resistant Gram-negative A. baumannii in vitro. The molecule was improved with regard to toxicity, as measured by hemolytic ability. Further, this peptide is capable of specifically killing non-growing cells of colistin resistant A...

  4. Peptides and the new endocrinology

    Science.gov (United States)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  5. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  6. An enhancer peptide for membrane-disrupting antimicrobial peptides

    Directory of Open Access Journals (Sweden)

    Zhang Hong

    2010-02-01

    Full Text Available Abstract Background NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4 by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn. Results In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against Staphylococcus aureus, whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P. Conclusions NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane.

  7. Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3',5'difluorophenyl)-alanine.

    Science.gov (United States)

    Martín-Gago, Pablo; Rol, Álvaro; Todorovski, Toni; Aragón, Eric; Martin-Malpartida, Pau; Verdaguer, Xavier; Vallès Miret, Mariona; Fernández-Carneado, Jimena; Ponsati, Berta; Macias, Maria J; Riera, Antoni

    2016-01-01

    Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1-5). We have designed six new Somatostatin analogs with L-3-(3',5'-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor aromatic ring in the network of aromatic interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aqueous solution by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a π-π interaction with the Phe present at 11 or 6, respectively. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin. PMID:27271737

  8. Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3′,5′difluorophenyl)-alanine

    Science.gov (United States)

    Martín-Gago, Pablo; Rol, Álvaro; Todorovski, Toni; Aragón, Eric; Martin-Malpartida, Pau; Verdaguer, Xavier; Vallès Miret, Mariona; Fernández-Carneado, Jimena; Ponsati, Berta; Macias, Maria J.; Riera, Antoni

    2016-01-01

    Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1–5). We have designed six new Somatostatin analogs with L-3-(3′,5′-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor aromatic ring in the network of aromatic interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aqueous solution by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a π-π interaction with the Phe present at 11 or 6, respectively. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin. PMID:27271737

  9. Strategic approaches to optimizing peptide ADME properties.

    Science.gov (United States)

    Di, Li

    2015-01-01

    Development of peptide drugs is challenging but also quite rewarding. Five blockbuster peptide drugs are currently on the market, and six new peptides received first marketing approval as new molecular entities in 2012. Although peptides only represent 2% of the drug market, the market is growing twice as quickly and might soon occupy a larger niche. Natural peptides typically have poor absorption, distribution, metabolism, and excretion (ADME) properties with rapid clearance, short half-life, low permeability, and sometimes low solubility. Strategies have been developed to improve peptide drugability through enhancing permeability, reducing proteolysis and renal clearance, and prolonging half-life. In vivo, in vitro, and in silico tools are available to evaluate ADME properties of peptides, and structural modification strategies are in place to improve peptide developability. PMID:25366889

  10. Histidine-Containing Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2000-01-01

    Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

  11. Lipoxygenase inhibitor peptides and their use

    OpenAIRE

    Schurink, M.; Boeriu, C.G.; Berkel, van, A.M.; Wichers, H J

    2006-01-01

    The present invention is in the field of enzyme inhibition. In particular it relates to peptide inhibitors for lipoxygenases. The lipoxygenase peptide inhibitors of have the potential to be used as therapeutic drugs as well as food preservatives.

  12. Natriuretic peptides in cardiometabolic regulation and disease

    DEFF Research Database (Denmark)

    Zois, Nora Elisabeth; Bartels, Emil Daniel; Hunter, Ingrid;

    2014-01-01

    decade. Dysregulation of the natriuretic peptide system has been associated with obesity, glucose intolerance, type 2 diabetes mellitus, and essential hypertension. Moreover, the natriuretic peptides have been implicated in the protection against atherosclerosis, thrombosis, and myocardial ischaemia. All...

  13. Purification, structure and function of bioactive peptides

    OpenAIRE

    Eriste, Elo

    2004-01-01

    Peptides are vitally important molecules and many evoke cellular responses. The completion of several genome sequencing projects has revealed a number of new genes. However, as functional peptides often contain posttranslational modifications and/or occur at various lengths, it is of great importance to detect, purify and characterize novel bioactive peptides. To achieve these goals, new methods for peptide detection, isolation and functional characterization have to be d...

  14. Development and use of engineered peptide deformylase in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia

    2012-01-01

    Deze thesis beschrijft het onderzoek naar potentieel van het gebruik van het peptide deformylase (PDF) in chemo enzymatische peptide synthese. PDF is geschikt voor selective N terminale deformylatie van bepaalde N-formyl-peptides zonder gelijktijdige hydrolyse van de peptide binding. Door de uitdagi

  15. Interpreting peptide mass spectra by VEMS

    DEFF Research Database (Denmark)

    Mathiesen, Rune; Lundsgaard, M.; Welinder, Karen G.;

    2003-01-01

    of peptide MS/MS spectra imported in text file format. Peaks are annotated, the monoisotopic peaks retained, and the b-and y-ion series identified in an interactive manner. The called peptide sequence is searched against a local protein database for sequence identity and peptide mass. The report compares...

  16. Synthetic Procedures for Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Characterization of synthetic peptides by mass spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala Krishna; Mirza, Osman Asghar; Højrup, Peter;

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an...

  18. Double-Stranded Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2001-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  19. Peptides and metallic nanoparticles for biomedical applications.

    NARCIS (Netherlands)

    Kogan, M.J.; Olmedo, I.; Hosta, L.; Guerrero, A.R.; Cruz Ricondo, L.J.; Albericio, F.

    2007-01-01

    In this review, we describe the contribution of peptides to the biomedical applications of metallic nanoparticles. We also discuss strategies for the preparation of peptide-nanoparticle conjugates and the synthesis of the peptides and metallic nanoparticles. An overview of the techniques used for th

  20. Diversity of wheat anti-microbial peptides.

    Science.gov (United States)

    Egorov, Tsezi A; Odintsova, Tatyana I; Pukhalsky, Vitaliy A; Grishin, Eugene V

    2005-11-01

    From seeds of Triticum kiharae Dorof. et Migusch., 24 novel anti-microbial peptides were isolated and characterized by a combination of three-step HPLC (affinity, size-exclusion and reversed-phase) with matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and Edman degradation. Based on sequence similarity and cysteine motifs, partially sequenced peptides were assigned to 7 families: defensins, thionins, lipid-transfer proteins, hevein-like peptides, knottin-like peptides, glycine-rich peptides, and MBP-1 homologs. A novel subfamily of defensins consisting of 6 peptides and a new family of glycine-rich (8 peptides with different repeat motifs) were identified. Three 6-cysteine knottin-like peptides represented by N- and C-terminally truncated variants revealed no sequence homology to any known plant anti-microbial peptides. A new 8-cysteine hevein-like peptide and three 4-cysteine peptides homologous to MBP-1 from maize were isolated. This is the first communication on the occurrence of nearly all families of plant anti-microbial peptides in a single species. PMID:16269343

  1. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  2. Bioactive peptides in dairy products

    Directory of Open Access Journals (Sweden)

    Donata Marletta

    2010-01-01

    Full Text Available Bioactive peptides are specific protein fragments that have a positive impact on body functions and conditions and may ultimately influence health. Most of the biological activities are encrypted within the primary sequence of the native protein and can be released by enzymatic hydrolysis and proteolysis or by food processing. Milk is a rich source of bioactive peptides which may contribute to regulate the nervous, gastrointestinal and cardiovascular systems as well as the immune system, confirming the added value of dairy products that, in certain cases, can be considered functional foods. The main biological activities of these peptides and their bioavailability in dairy products are reviewed. The natural concentration of these biomolecules is quite low and, to date one of the main goals has been to realize products enriched with bioactive peptides that have beneficial effects on human health and proven safety. Even though several health-enhancing products have already been launched and their integration in the diet could help in the prevention of chronic diseases such as hypertension, cancer and osteoporosis, more clinical trials are required in order to develop a deeper understanding of the activity of biopeptides on the human physiological mechanisms and also to assess the efficacy of their effects in a long term view. New scientific data are also needed to support their commercialisation in compliance with current regulations.

  3. Novel and Convenient Method for the Preparation of Phosphonate Peptides and Phosphonamidate Peptides

    Institute of Scientific and Technical Information of China (English)

    XU Jia-Xi; FU Nan-Yan; GAO Yuan-He; ZHNAG Qi-Han; DUAN Li-Fang

    2003-01-01

    @@ Phosphonate and phosphonamidate peptides are phosphorus analogues of natural peptides. They have been great used as stable mimetics of tetrahedral transition states as enzyme inhibitors and as haptens for catalytic antibody research in recent years. Although several methods are available for the preparation of phosphonate peptides and phosphonamidate peptides, all of them use phosphonic acid derivatives as starting materials. The overall yields from the synthesis of phosphonic acid derivatives to desired peptides are not satisfactory in most cases.

  4. Fabrication of Odor Sensor Using Peptide

    Science.gov (United States)

    Hotokebuchi, Yuta; Hayashi, Kenshi; Toko, Kiyoshi; Chen, Ronggang; Ikezaki, Hidekazu

    We report fabrication of an odor sensor using peptides. Peptides were designed to acquire the specific reception for a target odor molecule. Au surface of the sensor electrode was coated by the designed peptide using the method of self assembled monolayers (SAMs). Functionalized Au surfaces by the peptides were confirmed by ellipsometry and cyclic voltammetry. The odorants of vanillin, phenethyl alcohol and hexanol were discriminated by QCM sensor with the peptide surface. Moreover, we verified specific interaction between amino acid (Trp) and vanillin by fluorescence assay.

  5. Computer-Aided Design of Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Hancock, Robert E.W.; Jenssen, Håvard

    2010-01-01

    chemical parameters with biological activities of the peptide, using statistical methods. In this review we will discuss two different in silico strategies of computer-aided antibacterial peptide design, a linear correlation model build as an extension of traditional principal component analysis (PCA......) and a non-linear artificial neural network model. Studies on structurally diverse peptides, have concluded that the PCA derived model are able to guide the antibacterial peptide design in a meaningful way, however requiring rather a high homology between the peptides in the test-set and the in silico...

  6. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens;

    2013-01-01

    Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...... throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed...... that CPP-mediated translocation involves transcytosis and/or direct translocation through the epithelial cells; whereas TJMP-mediated translocation is dependent on interaction with transmembrane or peripheral TJ proteins. This review focuses on the CPPs and the TJMPs currently employed as excipients...

  7. Towards the MHC-peptide combinatorics.

    Science.gov (United States)

    Kangueane, P; Sakharkar, M K; Kolatkar, P R; Ren, E C

    2001-05-01

    The exponentially increased sequence information on major histocompatibility complex (MHC) alleles points to the existence of a high degree of polymorphism within them. To understand the functional consequences of MHC alleles, 36 nonredundant MHC-peptide complexes in the protein data bank (PDB) were examined. Induced fit molecular recognition patterns such as those in MHC-peptide complexes are governed by numerous rules. The 36 complexes were clustered into 19 subgroups based on allele specificity and peptide length. The subgroups were further analyzed for identifying common features in MHC-peptide binding pattern. The four major observations made during the investigation were: (1) the positional preference of peptide residues defined by percentage burial upon complex formation is shown for all the 19 subgroups and the burial profiles within entries in a given subgroup are found to be similar; (2) in class I specific 8- and 9-mer peptides, the fourth residue is consistently solvent exposed, however this observation is not consistent in class I specific 10-mer peptides; (3) an anchor-shift in positional preference is observed towards the C terminal as the peptide length increases in class II specific peptides; and (4) peptide backbone atoms are proportionately dominant at the MHC-peptide interface.

  8. Natural and synthetic peptides with antifungal activity.

    Science.gov (United States)

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections. PMID:27502155

  9. Flourescent Peptide-Stabilized Silver-Nanoclusters

    DEFF Research Database (Denmark)

    Gregersen, Simon

    for instance small molecules, DNA oligomers, and proteins. Peptides are an intriguing class of biomolecular ligands, due to the large combinatorial space these provide. Furthermore, as peptides have a propensity to fold up into well-defined and somewhat rigid secondary structures, they may serve as excellent...... throughput dramatically with regards to discovery of novel ligands. Our approach employs Fmoc solid-phase peptide synthesis on a PEGA resin which allows for on-resin screening of peptide ligands which, in turn, removes the tedious and labor-intensive work-up of synthesized peptides. The method allows for on......-resin formation of peptide-stabilized Ag-NCs in a reversible manner, which makes identification of novel lead compound from combinatorial peptide libraries possible with a few simple steps. This resulted in the discovery of at least one promising candidate (P262) showing brighter emission, spectral homogeneity...

  10. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions

    DEFF Research Database (Denmark)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco;

    2016-01-01

    . In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited...... for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions...... determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide...

  11. Encapsulation of bioactive whey peptides in soy lecithin-derived nanoliposomes: Influence of peptide molecular weight.

    Science.gov (United States)

    Mohan, Aishwarya; McClements, David Julian; Udenigwe, Chibuike C

    2016-12-15

    Encapsulation of peptides can be used to enhance their stability, delivery and bioavailability. This study focused on the effect of the molecular weight range of whey peptides on their encapsulation within soy lecithin-derived nanoliposomes. Peptide molecular weight did not have a major impact on encapsulation efficiency or liposome size. However, it influenced peptide distribution amongst the surface, core, and bilayer regions of the liposomes, as determined by electrical charge (ζ-potential) and FTIR analysis. The liposome ζ-potential depended on peptide molecular weight, suggesting that the peptide charged groups were in different locations relative to the liposome surfaces. FTIR analysis indicated that the least hydrophobic peptide fractions interacted more strongly with choline on the liposome surfaces. The results suggested that the peptides were unequally distributed within the liposomes, even at the same encapsulation efficiency. These findings are important for designing delivery systems for commercial production of encapsulated peptides with improved functional attributes. PMID:27451165

  12. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions.

    Science.gov (United States)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco; Østergaard, Jesper

    2016-10-10

    Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations.

  13. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  14. Antimicrobial peptides in human sepsis

    Directory of Open Access Journals (Sweden)

    Lukas eMartin

    2015-08-01

    Full Text Available Nearly 100 years ago, antimicrobial peptides (AMPs were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP 1-3 and human beta-defensins (HBDs 1-3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP -1-3 and HBD-2 in sepsis. The bactericidal/permeability increasing protein (BPI attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP-1-3, lactoferrin, BPI and heparin-binding protein (HBP are increased in sepsis. Human lactoferrin peptide 1-11 (hLF 1-11 possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin (talactoferrin alpha, TLF has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide (LPS. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe

  15. Antimicrobial Peptides: Versatile Biological Properties

    Directory of Open Access Journals (Sweden)

    Muthuirulan Pushpanathan

    2013-01-01

    Full Text Available Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries.

  16. Antihypertensive Peptides from Milk Proteins

    Directory of Open Access Journals (Sweden)

    Heikki Vapaatalo

    2010-01-01

    Full Text Available Dietary proteins possess a wide range of nutritional and functional properties. They are used as a source of energy and amino acids, which are needed for growth and development. Many dietary proteins, especially milk proteins, contain physiologically active peptides encrypted in the protein sequence. These peptides may be released during gastrointestinal digestion or food processing and once liberated, cause different physiological functions. Milk-derived bioactive peptides are shown to have antihypertensive, antimicrobial, immunomodulatory, antioxidative and mineral-binding properties. During the fermentation of milk with certain lactobacilli, two interesting tripeptides Ile-Pro-Pro and Val-Pro-Pro are released from casein to the final product. These lactotripeptides have attenuated the development of hypertension in several animal models and lowered blood pressure in clinical studies. They inhibit ACE in vitro at micromolar concentrations, protect endothelial function in vitro and reduce arterial stiffness in humans. Thus, milk as a traditional food product can after certain processing serve as a functional food and carry specific health-promoting effects, providing an option to control blood pressure.

  17. Chemical Methods for Peptide and Protein Production

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-04-01

    Full Text Available Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported a-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  18. Human Antimicrobial Peptides and Proteins

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2014-05-01

    Full Text Available As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32 can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized

  19. Molecular imaging probes derived from natural peptides.

    Science.gov (United States)

    Charron, C L; Hickey, J L; Nsiama, T K; Cruickshank, D R; Turnbull, W L; Luyt, L G

    2016-06-01

    Covering: up to the end of 2015.Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploited as diagnostic and therapeutic agents due to the unique target specificity for their endogenous receptors. This review discusses a variety of natural peptides highlighting their discovery, endogenous receptors, as well as their derivatization to create molecular imaging agents, with an emphasis on the design of radiolabelled peptides. This review also highlights methods for discovering new and novel peptides when knowledge of specific targets and endogenous ligands are not available. PMID:26911790

  20. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  1. Antimicrobial Peptides in Toroidal and Cylindrical Pores

    OpenAIRE

    Mihajlovic, Maja; Lazaridis, Themis

    2010-01-01

    Antimicrobial peptides (AMPs) are small, usually cationic peptides, which permeabilize biological membranes. Their mechanism of action is still not well understood. Here we investigate the preference of alamethicin and melittin for pores of different shapes, using molecular dynamics (MD) simulations of the peptides in pre-formed toroidal and cylindrical pores. When an alamethicin hexamer is initially embedded in a cylindrical pore, at the end of the simulation the pore remains cylindrical or ...

  2. Interaction of small peptides with lipid bilayers.

    OpenAIRE

    Damodaran, K. V.; Merz, K M; Gaber, B P

    1995-01-01

    Molecular dynamics simulations of the tripeptide Ala-Phe-Ala-O-tert-butyl interacting with dimyristoylphosphatidylcholine lipid bilayers have been carried out. The lipid and aqueous environments of the peptide, the alkyl chain order, and the lipid and peptide dynamics have been investigated with use of density profiles, radial distribution functions, alkyl chain order parameter profiles, and time correlation functions. It appears that the alkyl chain region accommodates the peptides in the bi...

  3. Self-assembly of tetraphenylalanine peptides

    OpenAIRE

    Mayans Tayadella, Enric; Ballano Ballano, María Gema; Casanovas Salas, Jordi; Díaz Andrade, Angélica María; Pérez Madrigal, Maria del Mar; Estrany Coda, Francesc; Puiggalí Bellalta, Jordi; Cativiela Marín, Carlos A.; Alemán Llansó, Carlos

    2015-01-01

    Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists o...

  4. Salt-resistant short antimicrobial peptides.

    Science.gov (United States)

    Mohanram, Harini; Bhattacharjya, Surajit

    2016-05-01

    Antimicrobial peptides (AMPs) are promising leads for the development of antibiotics against drug resistant bacterial pathogens. However, in vivo applications of AMPs remain obscure due to salt and serum mediated inactivation. The high cost of chemical synthesis of AMPs also impedes potential clinical application. Consequently, short AMPs resistant toward salt and serum inactivation are desirable for the development of peptide antibiotics. In this work, we designed a 12-residue amphipathic helical peptide RR12 (R-R-L-I-R-L-I-L-R-L-L-R-amide) and two Trp containing analogs of RR12 namely RR12Wpolar (R-R-L-I-W-L-I-L-R-L-L-R-amide), and RR12Whydro (R-R-L-I-R-L-W-L-R-L-L-R-amide). Designed peptides demonstrated potent antibacterial activity; MIC ranging from 2 to 8 μM, in the presence of sodium chloride (150 mM and 300 mM). Antibacterial activity of these peptides was also detected in the presence of human serum. Designed peptides, in particular RR12 and RR12Whydro, were only poorly hemolytic. As a mode of action; these peptides demonstrated efficient permeabilization of bacterial cell membrane and lysis of cell structure. We further investigated interactions of the designed peptides with lipopolysaccharide (LPS), the major component of the outer membrane permeability barrier of Gram-negative bacteria. Designed peptides adopted helical conformations in complex with LPS. Binding of peptides with LPS has yielded dissociation the aggregated structures of LPS. Collectively, these designed peptides hold ability to be developed for salt-resistant antimicrobial compounds. Most importantly, current work provides insights for designing salt-resistant antimicrobial peptides. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 345-356, 2016. PMID:26849911

  5. Genome-based peptide fingerprint scanning

    OpenAIRE

    Giddings, Michael C.; Shah, Atul A.; Gesteland, Ray; Moore, Barry

    2002-01-01

    We have implemented a method that identifies the genomic origins of sample proteins by scanning their peptide-mass fingerprint against the theoretical translation and proteolytic digest of an entire genome. Unlike previously reported techniques, this method requires no predefined ORF or protein annotations. Fixed-size windows along the genome sequence are scored by an equation accounting for the number of matching peptides, the number of missed enzymatic cleavages in each peptide, the number ...

  6. The Function and Development of Soybean Peptides

    Institute of Scientific and Technical Information of China (English)

    Yang Caiyan; Song Junmei

    2009-01-01

    Soybean peptides are small molecules hydrolyzed soy protein,from three to six amino acid composition of the peptide mixture,in 1000Da molecular weight below.Because it has a lot of good physical and chemical properties and physiological functions,in many areas has been widely used.This paper reviews the soybean peptide physical and chemical characteristics,physiological functions,technology and applications in the food industry.

  7. Insect inducible antimicrobial peptides and their applications.

    Science.gov (United States)

    Ezzati-Tabrizi, Reyhaneh; Farrokhi, Naser; Talaei-Hassanloui, Reza; Alavi, Seyed Mehdi; Hosseininaveh, Vahid

    2013-12-01

    Antimicrobial peptides (AMPs) are found as important components of the innate immune system (host defense) of all invertebrates. These peptides can be constitutively expressed or induced in response to microbial infections. Indeed, they vary in their amino acid sequences, potency and antimicrobial activity spectra. The smaller AMPs act greatly by disrupting the structure or function of microbial cell membranes. Here, the insect innate immune system with emphasis on inducible antimicrobial peptide properties against microbial invaders has been discussed.

  8. Modulation of autoimmunity with artificial peptides

    Science.gov (United States)

    La Cava, Antonio

    2010-01-01

    The loss of immune tolerance to self antigens leads to the development of autoimmune responses. Since self antigens are often multiple and/or their sequences may not be known, one approach to restore immune tolerance uses synthetic artificial peptides that interfere or compete with self peptides in the networks of cellular interactions that drive the autoimmune process. This review describes the rationale behind the use of artificial peptides in autoimmunity and their mechanisms of action. Examples of use of artificial peptides in preclinical studies and in the management of human autoimmune diseases are provided. PMID:20807590

  9. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...... pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending...... of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden....

  10. Synthetic peptide vaccines: palmitoylation of peptide antigens by a thioester bond increases immunogenicity

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.;

    1997-01-01

    or an amide bond. It was found that these S-palmitoylated peptides were much more immunogenic than N-palmitoylated peptides and at least similar to KLH-conjugated peptides with respect to appearance and magnitude of induced antibodies (canine parvovirus) or immunocastration effect (gonadotropin...

  11. Driving engineering of novel antimicrobial peptides from simulations of peptide-micelle interactions

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Langham, Allison A; Kaznessis, Yiannis N

    2006-01-01

    peptides and their interaction with membrane mimics. In this article, we discuss the promise and the challenges of widely used models and detail our recent work on peptide-micelle simulations as an attractive alternative to peptide-bilayer simulations. We detail our results with two large structural...

  12. Peptide Nucleic Acids Complexes of Two Peptide Nucleic Acid Strands and One

    DEFF Research Database (Denmark)

    1999-01-01

    Peptide nucleic acids and analogues of peptide nucleic acids are used to form duplex, triplex, and other structures with nucleic acids and to modify nucleic acids. The peptide nucleic acids and analogues thereof also are used to modulate protein activity through, for example, transcription arrest...

  13. Mechanism and kinetics of peptide partitioning into membranes from all-atom simulations of thermostable peptides

    OpenAIRE

    Ulmschneider, Martin B.; Doux, Jacques P F; Killian, J. Antoinette; Smith, Jeremy C.; Ulmschneider, Jakob P.

    2010-01-01

    Partitioning properties of transmembrane (TM) polypeptide segments directly determine membrane protein folding, stability, and function, and their understanding is vital for rational design of membrane active peptides. However, direct determination of water-to-bilayer transfer of TM peptides has proved difficult. Experimentally, sufficiently hydrophobic peptides tend to aggregate, while atomistic computer simulations at physiological temperatures cannot yet reach the long time scales required...

  14. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Deacon, C F; Holst, Jens Juul; Carr, R D

    1999-01-01

    Type 2 diabetes mellitus is a metabolic disease resulting in raised blood sugar which, if not satisfactorily controlled, can cause severe and often debilitating complications. Unfortunately, for many patients, the existing therapies do not give adequate control. Glucagon-like peptide-1 (GLP-1) is...... an incretin hormone which has a spectrum of activities which oppose the symptoms of diabetes. Of particular significance is the fact that these actions are glucose-dependent, meaning that the risk of severe hypoglycemia is practically eliminated. The recent elucidation of the key role of dipeptidyl...

  15. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens P; Holst Hansen, Lasse; Terzic, Dijana;

    2015-01-01

    Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

  16. Antimicrobial peptides in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    A Bogaerts

    2010-01-01

    Full Text Available The nematode Caenorhabditis elegans is one of the most successful model species for experimental research because of its sequenced genome, the versatile genetic toolkit and the straightforward breeding among others. In natural conditions however, this tiny worm is constantly surrounded by micro-organisms, simultaneously a source of indispensable nutrition and inevitable pathogens. Lacking an adaptive immune system, the worm solely relies on its innate immune defence to cope with its challenging life style. Hence C. elegans is an excellent model to gain more insight in innate immunity, which is remarkably preserved between invertebrate and vertebrate animals. The innate defence consists of receptors to detect potential pathogens, a complex network of signalling pathways and last but not least, effector molecules to abolish harmful microbes. In this review, we focus on the antimicrobial peptides, a vital subgroup of effector molecules. We summarise the current knowledge of the different families of C. elegans antimicrobial peptides, comprising NLPs, caenacins, ABFs, caenopores, and a recently discovered group with antifungal activity among which thaumatin-like proteins.

  17. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans;

    1990-01-01

    not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...... for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we...

  18. Determination of peptide content of DOTA-peptides by metal titration and UPLC

    International Nuclear Information System (INIS)

    Radiolabelled DOTA-peptides are in use for Peptide Receptor Radionuclide Scintigraphy (PRS) and Therapy (PRRT), e.g with 177Lu-DOTA-TATE or 90Y-DOTATOC. Labelling conditions are frequently critical. Therefore, the ingredients of the reaction, e.g. radiometal (90Y and 177Lu) and DOTA-peptide should be pure and the content known. Quality control of DOTA-peptide, can be performed with various methods, most commonly by UV. There are numerous conditions in which this is hampered, e.g. impurities may also have UV-absorption. The aim of the study was to quantify content and purity of DOTA-peptide

  19. Engineered Adhesion Peptides for Improved Silicon Adsorption.

    Science.gov (United States)

    Ramakrishnan, Sathish Kumar; Jebors, Said; Martin, Marta; Cloitre, Thierry; Agarwal, Vivechana; Mehdi, Ahmad; Martinez, Jean; Subra, Gilles; Gergely, Csilla

    2015-11-01

    Engineering peptides that present selective recognition and high affinity for a material is a major challenge for assembly-driven elaboration of complex systems with wide applications in the field of biomaterials, hard-tissue regeneration, and functional materials for therapeutics. Peptide-material interactions are of vital importance in natural processes but less exploited for the design of novel systems for practical applications because of our poor understanding of mechanisms underlying these interactions. Here, we present an approach based on the synthesis of several truncated peptides issued from a silicon-specific peptide recovered via phage display technology. We use the photonic response provided by porous silicon microcavities to evaluate the binding efficiency of 14 different peptide derivatives. We identify and engineer a short peptide sequence (SLVSHMQT), revealing the highest affinity for p(+)-Si. The molecular recognition behavior of the obtained peptide fragment can be revealed through mutations allowing identification of the preferential affinity of certain amino acids toward silicon. These results constitute an advance in both the engineering of peptides that reveal recognition properties for silicon and the understanding of biomolecule-material interactions.

  20. [Application on food preservative of antimicrobial peptides].

    Science.gov (United States)

    Zhao, Hongyan; Mu, Yu; Zhao, Baohua

    2009-07-01

    Antimicrobial peptides are an integral component of the innate immune system, it can counteract outer membrane pathogen such as bacteria, fungi, viruses, protozoan and so on. Owing to the sterilization and innocuity, it has the potential to be crude food preservative. In this paper the uses of antibacterial peptides in the food preservative were analyzed.

  1. Prediction of twin-arginine signal peptides

    DEFF Research Database (Denmark)

    Bendtsen, Jannick Dyrløv; Nielsen, Henrik; Widdick, D.;

    2005-01-01

    peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than...

  2. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies are...

  3. Peptide Mass Fingerprinting of Egg White Proteins

    Science.gov (United States)

    Alty, Lisa T.; LaRiviere, Frederick J.

    2016-01-01

    Use of advanced mass spectrometry techniques in the undergraduate setting has burgeoned in the past decade. However, relatively few undergraduate experiments examine the proteomics tools of protein digestion, peptide accurate mass determination, and database searching, also known as peptide mass fingerprinting. In this experiment, biochemistry…

  4. New Biodegradable Peptide-based Polymer Constructs

    NARCIS (Netherlands)

    van Dijk, M.

    2009-01-01

    Peptide-based polymers are of increasing interest, since they can be applied for a variety of purposes such as drug delivery devices, scaffolds for tissue engineering and -repair, and as novel biomaterials. Peptide-based polymers are common in nature and often exhibit special characteristics. Howeve

  5. Protein identification by peptide mass fingerprinting

    DEFF Research Database (Denmark)

    Hjernø, Karin

    2007-01-01

      Peptide mass fingerprinting is an effective way of identifying, e.g., gel-separated proteins, by matching experimentally obtained peptide mass data against large databases. However, several factors are known to influence the quality of the resulting matches, such as proteins contaminating the s...

  6. Peptidomic Identification of Serum Peptides Diagnosing Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Qiaojun Wen

    Full Text Available We sought to identify serological markers capable of diagnosing preeclampsia (PE. We performed serum peptide analysis (liquid chromatography mass spectrometry of 62 unique samples from 31 PE patients and 31 healthy pregnant controls, with two-thirds used as a training set and the other third as a testing set. Differential serum peptide profiling identified 52 significant serum peptides, and a 19-peptide panel collectively discriminating PE in training sets (n = 21 PE, n = 21 control; specificity = 85.7% and sensitivity = 100% and testing sets (n = 10 PE, n = 10 control; specificity = 80% and sensitivity = 100%. The panel peptides were derived from 6 different protein precursors: 13 from fibrinogen alpha (FGA, 1 from alpha-1-antitrypsin (A1AT, 1 from apolipoprotein L1 (APO-L1, 1 from inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, 2 from kininogen-1 (KNG1, and 1 from thymosin beta-4 (TMSB4. We concluded that serum peptides can accurately discriminate active PE. Measurement of a 19-peptide panel could be performed quickly and in a quantitative mass spectrometric platform available in clinical laboratories. This serum peptide panel quantification could provide clinical utility in predicting PE or differential diagnosis of PE from confounding chronic hypertension.

  7. B-Type allatostatins and sex peptides

    Science.gov (United States)

    In many species, mating induces a number of behavioral changes in the female. For Drosophila melanogaster, the sex peptide (SP) has been identified as the main molecular factor behind these responses. Recently, the sex peptide receptor (SPR), a GPCR activated by SP has also been characterized as res...

  8. Trandermal Peptides for Large Molecule Delivery

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ A research team, led by Prof. WEN Longping from the University of Science and Technology of China under CAS,has successfully screened out a trandermal peptide, using biotechnology. The new peptide is able to deliver insulin into human body through skin, rendering an immediate therapeutic effect. The finding was published in the March 27 issue of the journal Natural Biotechnology.

  9. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...

  10. Antioxidant activity of yoghurt peptides: Part 2 – Characterisationof peptide fractions

    DEFF Research Database (Denmark)

    Farvin, Sabeena; Baron, Caroline; Nielsen, Nina Skall;

    2010-01-01

    The aim of the present study was to elucidate previous findings showing that peptide fractions isolated from yoghurt had antioxidant effects. Therefore, peptides and free amino acids released during fermentation of milk were characterised. Yoghurt samples were stripped from sugars and lactic acid...... antioxidant activity in these fractions.......The aim of the present study was to elucidate previous findings showing that peptide fractions isolated from yoghurt had antioxidant effects. Therefore, peptides and free amino acids released during fermentation of milk were characterised. Yoghurt samples were stripped from sugars and lactic acid...... the peptides identified contained at least one proline residue. Some of the identified peptides included the hydrophobic amino acid residues Val or Leu at the N-terminus and Pro, His or Tyr in the amino acid sequence, which is characteristic of antioxidant peptides. In addition, the yoghurt contained...

  11. Role of peptide bond in the realization of biological activity of short peptides.

    Science.gov (United States)

    Khavinson, V Kh; Tarnovskaya, S I; Lin'kova, N S; Chervyakova, N A; Nichik, T E; Elashkina, E V; Chalisova, N I

    2015-02-01

    We performed a comparative analysis of biological activity of Lys-Glu peptide and its amino acid constituents. It was established that Lys-Glu stimulated proliferation of splenic cells in organotypic culture, while the mixture of glutamic acid and lysine inhibited culture growth. Using the method of molecular docking, we showed that glutamic acid, lysine, and Lys-Glu peptide can interact with different DNA sequences. The energy of interaction and the most beneficial localization of glutamic acid, lysine, and Lys-Glu peptide in DNA molecule was calculated. We demonstrated the interaction of the peptide and amino acids with DNA along the minor groove. The energy of DNA interaction with the peptide is higher than with individual amino acids. The peptide bonds increase the interaction of Lys-Glu peptide with DNA, which potentiates the biological effect on cell proliferation in organotypic culture of splenic cells.

  12. Peptide nanospheres self-assembled from a modified β-annulus peptide of Sesbania mosaic virus.

    Science.gov (United States)

    Matsuura, Kazunori; Mizuguchi, Yusaku; Kimizuka, Nobuo

    2016-11-01

    A novel β-annulus peptide of Sesbania mosaic virus bearing an FKFE sequence at the C terminus was synthesized, and its self-assembling behavior in water was investigated. Dynamic light scattering and transmission electron microscopy showed that the β-annulus peptide bearing an FKFE sequence self-assembled into approximately 30 nm nanospheres in water at pH 3.8, whereas the β-annulus peptide without the FKFE sequence afforded only irregular aggregates. The peptide nanospheres possessed a definite critical aggregation concentration (CAC = 26 μM), above which the size of nanospheres were nearly unaffected by the peptide concentration. The formation of peptide nanospheres was significantly affected by pH; the peptide did not form any assemblies at pH 2.2, whereas larger aggregates were formed at pH 6.4-11.6. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 470-475, 2016. PMID:26573103

  13. Design of Asymmetric Peptide Bilayer Membranes.

    Science.gov (United States)

    Li, Sha; Mehta, Anil K; Sidorov, Anton N; Orlando, Thomas M; Jiang, Zhigang; Anthony, Neil R; Lynn, David G

    2016-03-16

    Energetic insights emerging from the structural characterization of peptide cross-β assemblies have enabled the design and construction of robust asymmetric bilayer peptide membranes. Two peptides differing only in their N-terminal residue, phosphotyrosine vs lysine, coassemble as stacks of antiparallel β-sheets with precisely patterned charged lattices stabilizing the bilayer leaflet interface. Either homogeneous or mixed leaflet composition is possible, and both create nanotubes with dense negative external and positive internal solvent exposed surfaces. Cross-seeding peptide solutions with a preassembled peptide nanotube seed leads to domains of different leaflet architecture within single nanotubes. Architectural control over these cross-β assemblies, both across the bilayer membrane and along the nanotube length, provides access to highly ordered asymmetric membranes for the further construction of functional mesoscale assemblies.

  14. Intracellular signalling by C-peptide.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2008-01-01

    C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na(+)/K(+) ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes. PMID:18382618

  15. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  16. Antimicrobial peptides important in innate immunity.

    Science.gov (United States)

    Cederlund, Andreas; Gudmundsson, Gudmundur H; Agerberth, Birgitta

    2011-10-01

    Antimicrobial peptides are present in all walks of life, from plants to animals, and they are considered to be endogenous antibiotics. In general, antimicrobial peptides are determinants of the composition of the microbiota and they function to fend off microbes and prevent infections. Antimicrobial peptides eliminate micro-organisms through disruption of their cell membranes. Their importance in human immunity, and in health as well as disease, has only recently been appreciated. The present review provides an introduction to the field of antimicrobial peptides in general and discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins. The review focuses on their structures, their main modes of action and their regulation.

  17. Modelling water molecules inside cyclic peptide nanotubes

    Science.gov (United States)

    Tiangtrong, Prangsai; Thamwattana, Ngamta; Baowan, Duangkamon

    2016-03-01

    Cyclic peptide nanotubes occur during the self-assembly process of cyclic peptides. Due to the ease of synthesis and ability to control the properties of outer surface and inner diameter by manipulating the functional side chains and the number of amino acids, cyclic peptide nanotubes have attracted much interest from many research areas. A potential application of peptide nanotubes is their use as artificial transmembrane channels for transporting ions, biomolecules and waters into cells. Here, we use the Lennard-Jones potential and a continuum approach to study the interaction of a water molecule in a cyclo[(- D-Ala- L-Ala)_4-] peptide nanotube. Assuming that each unit of a nanotube comprises an inner and an outer tube and that a water molecule is made up of a sphere of two hydrogen atoms uniformly distributed over its surface and a single oxygen atom at the centre, we determine analytically the interaction energy of the water molecule and the peptide nanotube. Using this energy, we find that, independent of the number of peptide units, the water molecule will be accepted inside the nanotube. Once inside the nanotube, we show that a water molecule prefers to be off-axis, closer to the surface of the inner nanotube. Furthermore, our study of two water molecules inside the peptide nanotube supports the finding that water molecules form an array of a 1-2-1-2 file inside peptide nanotubes. The theoretical study presented here can facilitate thorough understanding of the behaviour of water molecules inside peptide nanotubes for applications, such as artificial transmembrane channels.

  18. Encapsulation of Enzymes and Peptides

    Science.gov (United States)

    Meesters, Gabrie M. H.

    A large part of formulated peptides and proteins, e.g., enzymes used as food ingredients, are formulated in a liquid form. Often, they are dissolved in water to which glycerol or sorbitol is added to reduce the water activity of the liquid, thus reducing the change of microbial growth. Still, there are reasons to formulate them in a solid form. Often, these reasons are stability, since a dry formulation is often much better than liquid formulations, and less transportation cost, since less mass is transported if one gets rid of the liquid; however, most of the times, the reason is that the product is mixed with a solid powder. Here, a liquid addition would lead to lump formation.

  19. Antimicrobial peptides of multicellular organisms

    Science.gov (United States)

    Zasloff, Michael

    2002-01-01

    Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

  20. Antimicrobial peptides in the brain.

    Science.gov (United States)

    Su, Yanhua; Zhang, Kai; Schluesener, Hermann J

    2010-10-01

    Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune system of many species. The brain is an immunologically privileged organ but can produce a robust immune response against pathogens and cell debris, promoting rapid and efficient clearance. AMPs may be critically involved in the innate immune system of the brain. Though the mechanisms of AMPs' action in the brain still need further elucidation, many studies have shown that AMPs are multifunctional molecules in the brain. In addition to antimicrobial action, they take part in congenital and adaptive immune reactions (immunoregulation), function as signaling molecules in tissue repair, inflammation and other important processes through different mechanisms, and they might, in addition, become diagnostic markers of brain disease.

  1. The novel amyloid-beta peptide aptamer inhibits intracellular amyloid-beta peptide toxicity

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Yi Yang; Mingyue Jia; Chi Ma; Mingyu Wang; Lihe Che; Yu Yang; Jiang Wu

    2013-01-01

    Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on peptide aptamers, the present study inserted ABAD-DP into the disulfide bond of human thioredoxin (TRX) using molecular cloning technique to construct a fusion gene that can express the TRX1-ABAD-DP-TRX2 aptamer. Moreover, adeno-associated virus was used to allow its stable expression. Immunofluorescent staining revealed the co-expression of the transduced fusion gene TRX1-ABAD-DP-TRX2 and amyloid β peptide in NIH-3T3 cells, indicating that the TRX1-ABAD-DP-TRX2 aptamer can bind amyloid β peptide within cells. In addition, cell morphology and MTT results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid β peptide-induced SH-SY5Y cell injury and improved cell viability. These findings confirmed the possibility of constructing TRX-based peptide aptamer using ABAD-DP. Moreover, TRX1-ABAD-DP-TRX2 inhibited the cytotoxic effect of amyloid β peptide.

  2. Interactions of Bio-Inspired Membranes with Peptides and Peptide-Mimetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Michael Sebastiano

    2015-08-01

    Full Text Available Via Dissipative Particle Dynamics (DPD and implicit solvent coarse-grained (CG Molecular Dynamics (MD we examine the interaction of an amphiphilic cell-penetrating peptide PMLKE and its synthetic counterpart with a bio-inspired membrane. We use the DPD technique to investigate the interaction of peptide-mimetic nanoparticles, or nanopins, with a three-component membrane. The CG MD approach is used to investigate the interaction of a cell-penetrating peptide PMLKE with single-component membrane. We observe the spontaneous binding and subsequent insertion of peptide and nanopin in the membrane by using CG MD and DPD approaches, respectively. In addition, we find that the insertion of peptide and nanopins is mainly driven by the favorable enthalpic interactions between the hydrophobic components of the peptide, or nanopin, and the membrane. Our study provides insights into the mechanism underlying the interactions of amphiphilic peptide and peptide-mimetic nanoparticles with a membrane. The result of this study can be used to guide the functional integration of peptide and peptide-mimetic nanoparticles with a cell membrane.

  3. Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Vegt, Erik; Eek, Annemarie; Oyen, Wim J.G.; Gotthardt, Martin; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine (444), PO Box 9101, Nijmegen (Netherlands); Jong, Marion de [Erasmus Medical Centre, Department of Nuclear Medicine, Rotterdam (Netherlands)

    2010-02-15

    In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of {sup 111}In-albumin, {sup 111}In-minigastrin, {sup 111}In-exendin and {sup 111}In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of {sup 111}In-minigastrin, {sup 111}In-exendin and {sup 111}In-octreotide was determined. FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of {sup 111}In-albumin, {sup 111}In-exendin and {sup 111}In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide 6), was selected for in vivo testing. In rats, 5 mg of peptide 6 very efficiently inhibited the renal uptake of {sup 111}In-minigastrin, by 88%. Uptake of {sup 111}In-exendin and {sup 111}In-octreotide was reduced by 26 and 33%, respectively. The albumin-derived peptide 6 efficiently inhibited the renal reabsorption of {sup 111}In-minigastrin, {sup 111}In-exendin and {sup 111}In-octreotide and is a promising candidate for kidney protection in PRRT. (orig.)

  4. rapmad: Robust analysis of peptide microarray data

    Directory of Open Access Journals (Sweden)

    Rothermel Andrée

    2011-08-01

    Full Text Available Abstract Background Peptide microarrays offer an enormous potential as a screening tool for peptidomics experiments and have recently seen an increased field of application ranging from immunological studies to systems biology. By allowing the parallel analysis of thousands of peptides in a single run they are suitable for high-throughput settings. Since data characteristics of peptide microarrays differ from DNA oligonucleotide microarrays, computational methods need to be tailored to these specifications to allow a robust and automated data analysis. While follow-up experiments can ensure the specificity of results, sensitivity cannot be recovered in later steps. Providing sensitivity is thus a primary goal of data analysis procedures. To this end we created rapmad (Robust Alignment of Peptide MicroArray Data, a novel computational tool implemented in R. Results We evaluated rapmad in antibody reactivity experiments for several thousand peptide spots and compared it to two existing algorithms for the analysis of peptide microarrays. rapmad displays competitive and superior behavior to existing software solutions. Particularly, it shows substantially improved sensitivity for low intensity settings without sacrificing specificity. It thereby contributes to increasing the effectiveness of high throughput screening experiments. Conclusions rapmad allows the robust and sensitive, automated analysis of high-throughput peptide array data. The rapmad R-package as well as the data sets are available from http://www.tron-mz.de/compmed.

  5. Conus Peptides A Rich Pharmaceutical Treasure

    Institute of Scientific and Technical Information of China (English)

    Cheng-Zhong WANG; Cheng-Wu CHI

    2004-01-01

    Marine predatory cone snails (genus Conus) with over 500 species represent what is arguably the largest single genus of marine animals alive today. All Conus are venomous and utilize a complex mixture of Conus peptides to capture their preys and for other biological purposes. Each component of Conus peptides selectively targets a specific subtype of ion channels, neurotransmitter receptors or transporters.Owing to their diversity, more than 50,000 distinct active peptides are theoretically estimated in Conus venoms. These diversified toxins are generally categorized into several superfamilies and/or families based on their characteristic arrangements of cysteine residues and pharmacological actions. Some mechanisms underlying the remarkable diversity of Conus peptides have been postulated: the distinctive gene structure, gene duplication and/or allelic selection, genus speciation, and sophisticated expression pattern and posttranslational modification of these peptides. Due to their highly pharmacological potency and target selectivity, Conus peptides have attracted extensive attention with their potentials to be developed as new research tools in neuroscience field and as novel medications in clinic for pain, epilepsy and other neuropathic disorders. Several instructive lessons for our drug development could be also learnt from these neuropharmacological "expertises". Conus peptides comprise a rich resource for neuropharmacologists, and most of them await to be explored.

  6. C-Peptide and its intracellular signaling.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2009-01-01

    Although long believed to be inert, C-peptide has now been shown to have definite biological effects both in vitro and in vivo in diabetic animals and in patients with type 1 diabetes. These effects point to a protective action of C-peptide against the development of diabetic microvascular complications. Underpinning these observations is undisputed evidence of C-peptide binding to a variety of cell types at physiologically relevant concentrations, and the downstream stimulation of multiple cell signaling pathways and gene transcription via the activation of numerous transcription factors. These pathways affect such fundamental cellular processes as re-absorptive and/or secretory phenotype, migration, growth, and survival. Whilst the receptor remains to be identified, experimental data points strongly to the existence of a specific G-protein-coupled receptor for C-peptide. Of the cell types studied so far, kidney tubular cells express the highest number of C-peptide binding sites. Accordingly, C-peptide exerts major effects on the function of these cells, and in the context of diabetic nephropathy appears to antagonise the pathophysiological effects of major disease mediators such as TGFbeta1 and TNFalpha. Therefore, based on its cellular activity profile C-peptide appears well positioned for development as a therapeutic tool to treat microvascular complications in type 1 diabetes. PMID:20039003

  7. Novel pH-Sensitive Cyclic Peptides.

    Science.gov (United States)

    Weerakkody, Dhammika; Moshnikova, Anna; El-Sayed, Naglaa Salem; Adochite, Ramona-Cosmina; Slaybaugh, Gregory; Golijanin, Jovana; Tiwari, Rakesh K; Andreev, Oleg A; Parang, Keykavous; Reshetnyak, Yana K

    2016-01-01

    A series of cyclic peptides containing a number of tryptophan (W) and glutamic acid (E) residues were synthesized and evaluated as pH-sensitive agents for targeting of acidic tissue and pH-dependent cytoplasmic delivery of molecules. Biophysical studies revealed the molecular mechanism of peptides action and localization within the lipid bilayer of the membrane at high and low pHs. The symmetric, c[(WE)4WC], and asymmetric, c[E4W5C], cyclic peptides translocated amanitin, a polar cargo molecule of similar size, across the lipid bilayer and induced cell death in a pH- and concentration-dependent manner. Fluorescently-labelled peptides were evaluated for targeting of acidic 4T1 mammary tumors in mice. The highest tumor to muscle ratio (5.6) was established for asymmetric cyclic peptide, c[E4W5C], at 24 hours after intravenous administration. pH-insensitive cyclic peptide c[R4W5C], where glutamic acid residues (E) were replaced by positively charged arginine residues (R), did not exhibit tumor targeting. We have introduced a novel class of cyclic peptides, which can be utilized as a new pH-sensitive tool in investigation or targeting of acidic tissue. PMID:27515582

  8. Creating functional peptide architectures at interfaces

    Science.gov (United States)

    Tirrell, Matthew

    2001-03-01

    Short peptide sequences, derived from whole proteins, can be useful synthetic agents for conferring a specific biological function to a material surface. Their ability to do this depends on delivering them to the surface in a biologically recognizable form, that is in a spatial configuration that is not too different from that adopted by the peptide in the whole protein. Most functional proteins have secondary and tertiary levels of structure that are essential to their activities; peptides have simpler but no less important structures. In our work, we have focussed on peptides derived from extracellular matrix proteins. We have found that attaching synthetic lipid tails to peptides fragments gives them two very useful properties for surface modification. The hydrophobic tails give rise to a self-assembly capacity enabling these molecules to organize into membrane, monolayer and bilayer structures. Less expected is that this level of self-assembly induces a second level in the peptide headgroup. Peptides from alpha-helical and triple-helical regions of protein are induced by the lipid tails to form protein-like secondary structures and therefore to have more effective biological activity.

  9. Peptide design for antimicrobial and immunomodulatory applications.

    Science.gov (United States)

    Haney, Evan F; Hancock, Robert E W

    2013-11-01

    The increasing threat of antibiotic resistance in pathogenic bacteria and the dwindling supply of antibiotics available to combat these infections poses a significant threat to human health throughout the world. Antimicrobial peptides (AMPs) have long been touted as the next generation of antibiotics capable of filling the anti-infective void. Unfortunately, peptide-based antibiotics have yet to realize their potential as novel pharmaceuticals, in spite of the immense number of known AMP sequences and our improved understanding of their antibacterial mechanism of action. Recently, the immunomodulatory properties of certain AMPs have become appreciated. The ability of small synthetic peptides to protect against infection in vivo has demonstrated that modulation of the innate immune response is an effective strategy to further develop peptides as novel anti-infectives. This review focuses on the screening methods that have been used to assess novel peptide sequences for their antibacterial and immunomodulatory properties. It will also examine how we have progressed in our ability to identify and optimize peptides with desired biological characteristics and enhanced therapeutic potential. In addition, the current challenges to the development of peptides as anti-infectives are examined and the strategies being used to overcome these issues are discussed.

  10. Immunocytochemical and Immunohistochemical Staining with Peptide Antibodies.

    Science.gov (United States)

    Friis, Tina; Pedersen, Klaus Boberg; Hougaard, David; Houen, Gunnar

    2015-01-01

    Peptide antibodies are particularly useful for immunocytochemistry (ICC) and immunohistochemistry (IHC), where antigens may denature due to fixation of tissues and cells. Peptide antibodies can be made to any defined sequence, including unknown putative proteins and posttranslationally modified sequences. Moreover, the availability of large amounts of the antigen (peptide) allows inhibition/adsorption controls, which are important in ICC/IHC, due to the many possibilities for false-positive reactions caused by immunoglobulin Fc receptors, nonspecific reactions, and cross-reactivity of primary and secondary antibodies with other antigens and endogenous immunoglobulins, respectively. Here, simple protocols for ICC and IHC are described together with recommendations for appropriate controls.

  11. Cysteine-containing peptides having antioxidant properties

    Science.gov (United States)

    Bielicki, John K.

    2008-10-21

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  12. Asymmetric catalysis with short-chain peptides.

    Science.gov (United States)

    Lewandowski, Bartosz; Wennemers, Helma

    2014-10-01

    Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically active peptides, which have addressed challenges that had thus far remained elusive in asymmetric catalysis: enantioselective synthesis of atropoisomers and quaternary stereogenic centers, regioselective transformations of polyfunctional substrates, chemoselective transformations, catalysis in-flow and reactions in aqueous environments.

  13. Peptides from milk proteins and their properties.

    Science.gov (United States)

    Kilara, Arun; Panyam, Dinakar

    2003-01-01

    This review has attempted to study the literature pertaining to peptides derived from milk proteins. Hydrolysis of milk proteins to generate peptides has been practiced for a long time and it was recognized early on in this process that the taste of hydrolyzates might hinder use of these products in food formulations. Modification of protein is necessary to form a more acceptable or utilizable product, to form a product that is less susceptible to deteriorative reactions and to form a product that is of higher nutritionall quality. Modifications may be achieved by a number of chemical and enzymatic means. This review has considered only enzymatic modification of dairy proteins. Modified proteins contain peptides and some of these peptides have been purified and their functionalities have been compared with unmodified proteins. This paper has examined the literature pertaining to improvement in functionality of enzyme-modified proteins. Improvements in solubility, emulsification, foaming and gelation were examined. There is limited information available on the sequence of the peptides necessary to improve the functional characteristics of proteins. Knowing the sequences of desirable functional peptides can lead to genetic alteration of proteins to improve functionality. Addition of synthetic peptides to intact proteins may be another way in which the functionality of proteins can be augmented. Some of the peptides in milk proteins are capable of affecting biological functions of an organism. These effects can be antimicrobial and probiotic, i.e., prevent the growth and proliferation of undesirable and pathogenic organisms, or they may promote the growth of desirable bacteria in the digestive tract of humans and animals. Peptides derived from milk protein have been shown to exert digestive and metabolic effects as well. They may also influence the immune system. These biological effects may play an important role in the development of medical foods that treat or

  14. Screening of a specific peptide binding to VPAC1 receptor from a phage display peptide library.

    Directory of Open Access Journals (Sweden)

    Bo Tang

    Full Text Available BACKGROUND/PURPOSE: The VPAC1 receptor, a member of the vasoactive intestinal peptide receptors (VIPRs, is overexpressed in the most frequently occurring malignant tumors and plays a major role in the progression and angiogenesis of a number of malignancies. Recently, phage display has become widely used for many applications, including ligand generation for targeted imaging, drug delivery and therapy. In this work, we developed a panning procedure using a phage display peptide library to select a peptide that specifically binds to the VPAC1 receptor to develop a novel targeted probe for molecular imaging and therapy. METHODS: CHO-K1 cells stably expressing VPAC1 receptors (CHO-K1/VPAC1 cells were used to select a VPAC1-binding peptide from a 12-mer phage peptide library. DNA sequencing and homologous analysis of the randomly selected phage clones were performed. A cellular ELISA was used to determine the most selectively binding peptide for further investigation. Binding specificity to the VPAC1 receptor was analyzed by competitive inhibition ELISA and flow cytometry. The binding ability of the selected peptide to CHO-K1/VPAC1 cells and colorectal cancer (CRC cell lines was confirmed using fluorescence microscopy and flow cytometry. RESULTS: A significant enrichment of phages that specifically bound to CHO-K1/VPAC1 cells was obtained after four rounds of panning. Of the selected phage clones, 16 out of 60 shared the same peptide sequence, GFRFGALHEYNS, which we termed the VP2 peptide. VP2 and vasoactive intestinal peptide (VIP competitively bound to the VPAC1 receptor. More importantly, we confirmed that VP2 specifically bound to CHO-K1/VPAC1 cells and several CRC cell lines. CONCLUSION: Our results demonstrate that the VP2 peptide could specifically bind to VPAC1 receptor and several CRC cell lines. And VP2 peptide may be a potential candidate to be developed as a useful diagnostic molecular imaging probe for early detection of CRC.

  15. A Peptide & Peptide Nucleic Acid Synthesis Technology for Transporter Molecules and Theranostics - The SPPS

    OpenAIRE

    Pipkorn, Ruediger; Braun, Klaus; Wiessler, Manfred; Waldeck, Waldemar; Schrenk, Hans-Hermann; Koch, Mario; Semmler, Wolfhard; Komljenovic, Dorde

    2014-01-01

    Advances in imaging diagnostics using magnetic resonance tomography (MRT), positron emission tomography (PET) and fluorescence imaging including near infrared (NIR) imaging methods are facilitated by constant improvement of the concepts of peptide synthesis. Feasible patient-specific theranostic platforms in the personalized medicine are particularly dependent on efficient and clinically applicable peptide constructs. The role of peptides in the interrelations between the structure and functi...

  16. Collagen-like peptides and peptide-polymer conjugates in the design of assembled materials

    OpenAIRE

    Luo, Tianzhi; Kiick, Kristi L.

    2013-01-01

    Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLP), also known as collagen-mimetic peptides (CMP) or collagen-related peptides (CRP), have thus been widely used to elucidate collagen triple helix structure as well as to produce higher-order structures that mimic natural collagen fibers. This mini-review provides an overview of recent progress...

  17. A statistical approach to determining responses to individual peptides from pooled-peptide ELISpot data.

    Science.gov (United States)

    Ström, Peter; Støer, Nathalie; Borthwick, Nicola; Dong, Tao; Hanke, Tomáš; Reilly, Marie

    2016-08-01

    To investigate in detail the effect of infection or vaccination on the human immune system, ELISpot assays are used to simultaneously test the immune response to a large number of peptides of interest. Scientists commonly use "peptide pools", where, instead of an individual peptide, a test well contains a group of peptides. Since the response from a well may be due to any or many of the peptides in the pool, pooled assays usually need to be followed by confirmatory assays of a number of individual peptides. We present a statistical method that enables estimation of individual peptide responses from pool responses using the Expectation Maximization (EM) algorithm for "incomplete data". We demonstrate the accuracy and precision of these estimates in simulation studies of ELISpot plates with 90 pools of 6 or 7 peptides arranged in three dimensions and three Mock wells for the estimation of background. In analysis of real pooled data from 6 subjects in a HIV-1 vaccine trial, where 199 peptides were arranged in 80 pools if size 9 or 10, our estimates were in very good agreement with the results from individual-peptide confirmatory assays. Compared to the classical approach, we could identify almost all the same peptides with high or moderate response, with less than half the number of confirmatory tests. Our method facilitates efficient use of the information available in pooled ELISpot data to avoid or reduce the need for confirmatory testing. We provide an easy-to-use free online application for implementing the method, where on uploading two spreadsheets with the pool design and pool responses, the user obtains the estimates of the individual peptide responses. PMID:27196788

  18. Peptide Internalization Enabled by Folding: Triple Helical Cell-Penetrating Peptides

    OpenAIRE

    Shinde, Aparna; Feher, Katie M.; Hu, Chloe; Slowinska, Katarzyna

    2014-01-01

    Cell-Penetrating Peptides (CPPs) are known as efficient transporters of molecular cargo across cellular membranes. Their properties make them ideal candidates for in vivo applications. However, challenges in development of effective CPPs still exist: CPPs are often fast degraded by proteases and large concentration of CPPs required for cargo transporting can cause cytotoxicity. It was previously shown that restricting peptide flexibility can improve peptide stability against enzymatic degrada...

  19. Determination of peptide content and purity of DOTA-peptides by metal ion titration and UPLC. An alternative method to monitor quality of DOTA-peptides

    International Nuclear Information System (INIS)

    PRRT requires high specific activities, thus at low molar ratio between DOTA-peptide and radioactivity. Therefore, the ingredients of the reaction, including (radio)metals and DOTA-peptide must be pure and the content known. Our aim was to quantify content and purity of DOTA-peptide by a base-to-base separation of DOTA-peptide and metal-DOTA-peptide by UPLC and UV-detection. Quantification of these peaks reveals an accurate and sensitive method to quantify purity and content of DOTA-peptides. Moreover, this technique enables monitoring of the (radio)labeling process and co-introduction of impurities, including metal ions. (author)

  20. Charge Transport Phenomena in Peptide Molecular Junctions

    Directory of Open Access Journals (Sweden)

    Alessandra Luchini

    2008-01-01

    Full Text Available Inelastic electron tunneling spectroscopy (IETS is a valuable in situ spectroscopic analysis technique that provides a direct portrait of the electron transport properties of a molecular species. In the past, IETS has been applied to small molecules. Using self-assembled nanoelectronic junctions, IETS was performed for the first time on a large polypeptide protein peptide in the phosphorylated and native form, yielding interpretable spectra. A reproducible 10-fold shift of the I/V characteristics of the peptide was observed upon phosphorylation. Phosphorylation can be utilized as a site-specific modification to alter peptide structure and thereby influence electron transport in peptide molecular junctions. It is envisioned that kinases and phosphatases may be used to create tunable systems for molecular electronics applications, such as biosensors and memory devices.

  1. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.;

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit...

  2. Ribosomally synthesized peptides from natural sources.

    Science.gov (United States)

    Singh, Nidhi; Abraham, Jayanthi

    2014-04-01

    There are many antibiotic-resistant microbial pathogens that have emerged in recent years causing normal infections to become harder and sometimes impossible to treat. The major mechanisms of acquired resistance are the ability of the microorganisms to destroy or modify the drug, alter the drug target, reduce uptake or increase efflux of the drug and replace the metabolic step targeted by the drug. However, in recent years, resistant strains have been reported from almost every environment. New antimicrobial compounds are of major importance because of the growing problem of bacterial resistance, and antimicrobial peptides have been gaining a lot of interest. Their mechanism of action, however, is often obscure. Antimicrobial peptides are widespread and have a major role in innate immunity. An increasing number of peptides capable of inhibiting microbial growth are being reviewed here. In this article, we consider the possible use of antimicrobial peptides against pathogens.

  3. Evolution of Antimicrobial Peptides to Self-Assembled Peptides for Biomaterial Applications

    Directory of Open Access Journals (Sweden)

    Alice P. McCloskey

    2014-10-01

    Full Text Available Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides harness a “bottom-up” approach, whereby the primary peptide sequence may be modified with natural and unnatural amino acids to produce an inherently antimicrobial hydrogel. Gelation may be tailored to occur in the presence of physiological and infective indicators (e.g. pH, enzymes and therefore allow local, targeted antimicrobial therapy at the site of infection. Peptides demonstrate inherent biocompatibility, antimicrobial activity, biodegradability and numerous functional groups. They are therefore prime candidates for the production of polymeric molecules that have the potential to be conjugated to biomaterials with precision. Non-native chemistries and functional groups are easily incorporated into the peptide backbone allowing peptide hydrogels to be tailored to specific functional requirements. This article reviews an area of increasing interest, namely self-assembled peptides and their potential therapeutic applications as innovative hydrogels and biomaterials in the prevention of biofilm-related infection.

  4. From a pro-apoptotic peptide to a lytic peptide: One single residue mutation.

    Science.gov (United States)

    Zhou, Xi-Rui; Zhang, Qiang; Tian, Xi-Bo; Cao, Yi-Meng; Liu, Zhu-Qing; Fan, Ruru; Ding, Xiu-Fang; Zhu, Zhentai; Chen, Long; Luo, Shi-Zhong

    2016-08-01

    Further discovery and design of new anticancer peptides are important for the development of anticancer therapeutics, and study on the detailed acting mechanism and structure-function relationship of peptides is critical for anticancer peptide design and application. In this study, a novel anticancer peptide ZXR-1 (FKIGGFIKKLWRSKLA) derived from a known anticancer peptide mauriporin was developed, and a mutant ZXR-2 (FKIGGFIKKLWRSLLA) with only one residue difference at the 14th position (Lys→Leu) was also engineered. Replacement of the lysine with leucine made ZXR-2 more potent than ZXR-1 in general. Even with only one residue mutation, the two peptides displayed distinct anticancer modes of action. ZXR-1 could translocate into cells, target on the mitochondria and induce cell apoptosis, while ZXR-2 directly targeted on the cell membranes and caused membrane lysis. The variance in their acting mechanisms might be due to the different amphipathicity and positive charge distribution. In addition, the two Ile-Leu pairs (3-10 and 7-14) in ZXR-2 might also play a role in improving its cytotoxicity. Further study on the structure-function relationship of the two peptides may be beneficial for the design of novel anticancer peptides and peptide based therapeutics. PMID:27207743

  5. Gene Transfer with Poly-Melittin Peptides

    OpenAIRE

    Chen, Chang-Po; Kim, Ji-Seon; Steenblock, Erin; Liu, Dijie; Rice, Kevin G.

    2006-01-01

    The 26 amino acid hemolytic melittin peptide was converted into a gene transfer peptide that binds to DNA and polymerized through disulfide bond formation. Melittin analogues were synthesized by addition of one to four Lys repeats at either the C or N-subterminal end along with terminal Cys residues. Melittin analogues were able to bind and polymerize on plasmids resulting in the formation of DNA condensates. In the absence of DNA, melittin analogues retained their red blood cell hemolytic po...

  6. Bioactive peptides and proteins in disease

    OpenAIRE

    Refai, Essam

    2004-01-01

    Regulatory peptides and marker proteins are important to study in order to understand disease mechanisms. This applies of course also to our common diseases where all relationships are not yet known. Cancer and diabetes are two such complex diseases that affect hundreds of millions of people worldwide. This thesis addresses particular aspects of these two diseases, regarding one regulatory peptide (VIP, vasoactive intestinal polypeptide) that may be useful for tumor tracing ...

  7. Natriuretic peptides, obesity and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Yaniel Castro-Torres

    2015-02-01

    Full Text Available Obesity, hypertension and heart failure are conditions commonly associated with each other. Recent investigations have demonstrated that low plasmatic levels of natriuretic peptides are linked with obesity. Thus, knowing the actions of these hormones in water and salt homeostasis, it is possible to establish that low levels of natriuretic peptides may be the common denominator among obesity, hypertension and heart failure. Knowledge on this topic is crucial to develop further investigation for definitive conclusions.

  8. Dietary fiber, gut peptides, and adipocytokines

    OpenAIRE

    Sánchez, David; Miguel, Marta; Aleixandre, Amaya

    2012-01-01

    The consumption of dietary fiber (DF) has increased since it was related to the prevention of a range of illnesses and pathological conditions. DF can modify some gut hormones that regulate satiety and energy intake, thus also affecting lipid metabolism and energy expenditure. Among these gut hormones are ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin. Adipose tissue is known to express and secrete a variety of products known as >adipocytokines,> which are also affected by ...

  9. Peptide oligomers for holographic data storage

    DEFF Research Database (Denmark)

    Berg, Rolf Henrik; Hvilsted, Søren; Ramanujam, P.S.

    1996-01-01

    SEVERAL classes of organic materials (such as photoanisotropic liquid-crystalline polymers(1-4) and photorefractive polymers(5-7)) are being investigated for the development of media for optical data storage. Here we describe a new family of organic materials-peptide oligomers containing azobenze....... Straightforward extension of this peptide-based strategy to other molecular structures should allow the rational design of a wide range of organic materials with potentially useful optical properties....

  10. From antimicrobial to anticancer peptides. A review.

    OpenAIRE

    Diana eGaspar; A. Salomé eVeiga; Miguel A.R.B. eCastanho

    2013-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective...

  11. Liquid-phase synthesis of bridged peptides using olefin metathesis of a protected peptide with a long aliphatic chain anchor.

    Science.gov (United States)

    Aihara, Keisuke; Komiya, Chiaki; Shigenaga, Akira; Inokuma, Tsubasa; Takahashi, Daisuke; Otaka, Akira

    2015-02-01

    Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported.

  12. Affinity-based release of polymer-binding peptides from hydrogels with the target segments of peptides.

    Science.gov (United States)

    Serizawa, Takeshi; Fukuta, Hiroki; Date, Takaaki; Sawada, Toshiki

    2016-02-01

    Peptides with affinities for the target segments of polymer hydrogels were identified by biological screening using phage-displayed peptide libraries, and these peptides exhibited an affinity-based release capability from hydrogels. The results from cell culture assays demonstrated the sustained anticancer effects of the drug-conjugated peptides that were released from the hydrogels.

  13. Membrane manufacture for peptide separations

    KAUST Repository

    Kim, DooLi

    2016-06-07

    Nanostructured polymeric membranes are key tools in biomedical applications such as hemodialysis, protein separations, in the food industry, and drinking water supply from seawater. Despite of the success in different separation processes, membrane manufacture itself is at risk, since the most used solvents are about to be banned in many countries due to environmental and health issues. We propose for the first time the preparation of polyethersulfone membranes based on dissolution in the ionic liquid 1-ethyl-3-methylimidazolium dimethylphosphate ([EMIM]DEP). We obtained a series of membranes tailored for separation of solutes with molecular weight of 30, 5, 1.3, and 1.25 kg mol-1 with respective water permeances of 140, 65, 30 and 20 Lm-2h-1bar-1. We demonstrate their superior efficiency in the separation of complex mixtures of peptides with molecular weights in the range of 800 to 3500 gmol-1. Furthermore, the thermodynamics and kinetics of phase separation leading to the pore formation in the membranes were investigated. The rheology of the solutions and the morphology of the prepared membranes were examed and compared to those of polyethersulfone in organic solvents currently used for membrane manufacture.

  14. Tryptophan rotamer distributions in amphipathic peptides at a lipid surface.

    OpenAIRE

    Clayton, A H; Sawyer, W. H.

    1999-01-01

    The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. We describe the use of frequency domain fluorescence spectroscopy to determine the conformational and environmental changes associated with the interaction of single tryptophan amphipathic peptides with a phospholipid surface. The five 18-residue peptides studied are based on a class A amphipathic peptide known to associate with lipid bilayers. The peptides contain a single tryp...

  15. Stereo-separations of Peptides by Capillary Electrophoresis and Chromatography

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Afzal Hussain, Iqbal Hussain, Mohamed F. Al-Ajmi & Imran Ali ### Abstract Small peptides (di-, tri-, tetra- penta- hexa etc. and peptides) control many chemical and biological processes. The biological importance of stereomers of peptides is of great value. The stereo-separations of peptides are gaining importance in biological and medicinal sciences and pharmaceutical industries. There is a great need of experimental protocols of stereo-separations of peptides. The vario...

  16. Relaxin family peptides and their receptors.

    Science.gov (United States)

    Bathgate, R A D; Halls, M L; van der Westhuizen, E T; Callander, G E; Kocan, M; Summers, R J

    2013-01-01

    There are seven relaxin family peptides that are all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Insulin-like peptide-3 (INSL3) has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. Although they are structurally related to insulin, the relaxin family peptides produce their physiological effects by activating a group of four G protein-coupled receptors (GPCRs), relaxin family peptide receptors 1-4 (RXFP1-4). Relaxin and INSL3 are the cognate ligands for RXFP1 and RXFP2, respectively, that are leucine-rich repeat containing GPCRs. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and activate MAP kinases. Although there are still many unanswered questions regarding the mode of action of relaxin family peptides, it is clear that they have important physiological roles that could be exploited for therapeutic benefit. PMID:23303914

  17. Confinement-dependent friction in peptide bundles.

    Science.gov (United States)

    Erbaş, Aykut; Netz, Roland R

    2013-03-19

    Friction within globular proteins or between adhering macromolecules crucially determines the kinetics of protein folding, the formation, and the relaxation of self-assembled molecular systems. One fundamental question is how these friction effects depend on the local environment and in particular on the presence of water. In this model study, we use fully atomistic MD simulations with explicit water to obtain friction forces as a single polyglycine peptide chain is pulled out of a bundle of k adhering parallel polyglycine peptide chains. The whole system is periodically replicated along the peptide axes, so a stationary state at prescribed mean sliding velocity V is achieved. The aggregation number is varied between k = 2 (two peptide chains adhering to each other with plenty of water present at the adhesion sites) and k = 7 (one peptide chain pulled out from a close-packed cylindrical array of six neighboring peptide chains with no water inside the bundle). The friction coefficient per hydrogen bond, extrapolated to the viscous limit of vanishing pulling velocity V → 0, exhibits an increase by five orders of magnitude when going from k = 2 to k = 7. This dramatic confinement-induced friction enhancement we argue to be due to a combination of water depletion and increased hydrogen-bond cooperativity. PMID:23528088

  18. Peptide pheromone signaling in Streptococcus and Enterococcus.

    Science.gov (United States)

    Cook, Laura C; Federle, Michael J

    2014-05-01

    Intercellular chemical signaling in bacteria, commonly referred to as quorum sensing (QS), relies on the production and detection of compounds known as pheromones to elicit coordinated responses among members of a community. Pheromones produced by Gram-positive bacteria are comprised of small peptides. Based on both peptide structure and sensory system architectures, Gram-positive bacterial signaling pathways may be classified into one of four groups with a defining hallmark: cyclical peptides of the Agr type, peptides that contain Gly-Gly processing motifs, sensory systems of the RNPP family, or the recently characterized Rgg-like regulatory family. The recent discovery that Rgg family members respond to peptide pheromones increases substantially the number of species in which QS is likely a key regulatory component. These pathways control a variety of fundamental behaviors including conjugation, natural competence for transformation, biofilm development, and virulence factor regulation. Overlapping QS pathways found in multiple species and pathways that utilize conserved peptide pheromones provide opportunities for interspecies communication. Here we review pheromone signaling identified in the genera Enterococcus and Streptococcus, providing examples of all four types of pathways.

  19. SPdb – a signal peptide database

    Directory of Open Access Journals (Sweden)

    Tan Tin

    2005-10-01

    Full Text Available Abstract Background The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database http://proline.bic.nus.edu.sg/spdb, a repository of experimentally determined and computationally predicted signal peptides. Results SPdb integrates information from two sources (a Swiss-Prot protein sequence database which is now part of UniProt and (b EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. Conclusion SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date.

  20. Antimicrobial cyclic peptides for plant disease control.

    Science.gov (United States)

    Lee, Dong Wan; Kim, Beom Seok

    2015-03-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  1. Antimicrobial Cyclic Peptides for Plant Disease Control

    Directory of Open Access Journals (Sweden)

    Dong Wan Lee

    2015-03-01

    Full Text Available Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  2. Self-Assembly of Tetraphenylalanine Peptides.

    Science.gov (United States)

    Mayans, Enric; Ballano, Gema; Casanovas, Jordi; Díaz, Angélica; Pérez-Madrigal, Maria M; Estrany, Francesc; Puiggalí, Jordi; Cativiela, Carlos; Alemán, Carlos

    2015-11-16

    Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head-to-tail NH3(+)⋅⋅⋅(-)OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N-fluorenylmethoxycarbonyl (Fmoc) protected FFFF self-assembles into a variety of polymorphs: ultra-thin nanoplates, fibrils, and star-like submicrometric aggregates. DFT calculations indicate that Fmoc-FFFF prefers a parallel rather than an antiparallel β-sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc-FFFF-OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic. PMID:26419936

  3. Biomathematical description of synthetic peptide libraries.

    Directory of Open Access Journals (Sweden)

    Timo Sieber

    Full Text Available Libraries of randomised peptides displayed on phages or viral particles are essential tools in a wide spectrum of applications. However, there is only limited understanding of a library's fundamental dynamics and the influences of encoding schemes and sizes on their quality. Numeric properties of libraries, such as the expected number of different peptides and the library's coverage, have long been in use as measures of a library's quality. Here, we present a graphical framework of these measures together with a library's relative efficiency to help to describe libraries in enough detail for researchers to plan new experiments in a more informed manner. In particular, these values allow us to answer-in a probabilistic fashion-the question of whether a specific library does indeed contain one of the "best" possible peptides. The framework is implemented in a web-interface based on two packages, discreteRV and peptider, to the statistical software environment R. We further provide a user-friendly web-interface called PeLiCa (Peptide Library Calculator, http://www.pelica.org, allowing scientists to plan and analyse their peptide libraries.

  4. Peptide Toxins in Solitary Wasp Venoms

    Science.gov (United States)

    Konno, Katsuhiro; Kazuma, Kohei; Nihei, Ken-ichi

    2016-01-01

    Solitary wasps paralyze insects or spiders with stinging venom and feed the paralyzed preys to their larva. Accordingly, the venoms should contain a variety of constituents acting on nervous systems. However, only a few solitary wasp venoms have been chemically studied despite thousands of species inhabiting the planet. We have surveyed bioactive substances in solitary wasp venoms found in Japan and discovered a variety of novel bioactive peptides. Pompilidotoxins (PMTXs), in the venoms of the pompilid wasps Anoplius samariensis and Batozonellus maculifrons, are small peptides consisting of 13 amino acids without a disulfide bond. PMTXs slowed Na+ channel inactivation, in particular against neuronal type Na+ channels, and were rather selective to the Nav1.6 channel. Mastoparan-like cytolytic and antimicrobial peptides are the major components of eumenine wasp venoms. They are rich in hydrophobic and basic amino acids, adopting a α-helical secondary structure, and showing mast cell degranulating, antimicrobial and hemolytic activities. The venom of the spider wasp Cyphononyx fulvognathus contained four bradykinin-related peptides. They are hyperalgesic and, dependent on the structure, differently associated with B1 or B2 receptors. Further survey led to the isolation of leucomyosuppressin-like FMRFamide peptides from the venoms of the digger wasps Sphex argentatus and Isodontia harmandi. These results of peptide toxins in solitary wasp venoms from our studies are summarized. PMID:27096870

  5. Peptide Toxins in Solitary Wasp Venoms

    Directory of Open Access Journals (Sweden)

    Katsuhiro Konno

    2016-04-01

    Full Text Available Solitary wasps paralyze insects or spiders with stinging venom and feed the paralyzed preys to their larva. Accordingly, the venoms should contain a variety of constituents acting on nervous systems. However, only a few solitary wasp venoms have been chemically studied despite thousands of species inhabiting the planet. We have surveyed bioactive substances in solitary wasp venoms found in Japan and discovered a variety of novel bioactive peptides. Pompilidotoxins (PMTXs, in the venoms of the pompilid wasps Anoplius samariensis and Batozonellus maculifrons, are small peptides consisting of 13 amino acids without a disulfide bond. PMTXs slowed Na+ channel inactivation, in particular against neuronal type Na+ channels, and were rather selective to the Nav1.6 channel. Mastoparan-like cytolytic and antimicrobial peptides are the major components of eumenine wasp venoms. They are rich in hydrophobic and basic amino acids, adopting a α-helical secondary structure, and showing mast cell degranulating, antimicrobial and hemolytic activities. The venom of the spider wasp Cyphononyx fulvognathus contained four bradykinin-related peptides. They are hyperalgesic and, dependent on the structure, differently associated with B1 or B2 receptors. Further survey led to the isolation of leucomyosuppressin-like FMRFamide peptides from the venoms of the digger wasps Sphex argentatus and Isodontia harmandi. These results of peptide toxins in solitary wasp venoms from our studies are summarized.

  6. Human C-peptide. Pt. 1

    International Nuclear Information System (INIS)

    Synthetic human C-peptide bearing a tyrosine group at its amino end is labelled with 125iodine using chloramin T or hydrogen peroxide and lactoperoxidase. The results of the two methods are compared. Antiserum to synthetic human C-peptide (without tyrosine), which was partially coupled to rabbit albumin, is raised in guinea pigs and goats. Goats show to be superior to guinea pips concerning antibody production. The so-called 'hook effect' phenomenon is observed when setting up the standard curves for the radioimmunoassay. Monotonically decreasing standard curves are obtained on dilution of antiserum with a high antibody titer which was produced by repeated immunization in goats. Free C-peptide and C-peptide bound to antiserum are separated using the anion exchange resin amberlite. Using this separation technique we excluded unspecific binding of labelled C-peptide to protein fractions in serum of diabetics. The sensitivity of our radioimmunoassay is approx. 0.3 ng C-peptide/ml serum. Intra- and interassay variability are below 10%. Human proinsulin is the only substance found to crossreact with the antiserum. (orig.)

  7. Effects of opioid peptides on thermoregulation

    Energy Technology Data Exchange (ETDEWEB)

    Clark, W.G.

    1981-11-01

    In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic peptide analogs do not necessarily evoke the same response as does the related endogenous peptide. The lack of effect of naloxone on body temperature of subjects housed at usual laboratory temperature or on pyrogen-induced increases in body temperature indicates that an action of endogenous peptides on naloxone-sensitive receptors plays little, if any, role in normal thermoregulation or in fever. However, there is some evidence that such an action may be involved in responses to restraint or ambient temperature-induced stress. Further evaluation of possible physiological roles of endogenous opioid peptides will be facilitated when specific antagonists at other types of opioid receptors become available.

  8. A cocoa peptide protects Caenorhabditis elegans from oxidative stress and β-amyloid peptide toxicity.

    Directory of Open Access Journals (Sweden)

    Patricia Martorell

    Full Text Available BACKGROUND: Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. METHODOLOGY/PRINCIPAL FINDINGS: A bioactive peptide, 13L (DNYDNSAGKWWVT, was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aβ₁₋₄₂ peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL showed the highest antioxidant activity (P≤0.001 in the wild-type strain (N2. Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24-47 h period after Aβ₁₋₄₂ peptide induction (P≤0.0001. This observation is in accordance with the reduction of Aβ deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aβ deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.

  9. Interaction of antimicrobial peptides with lipid membranes

    International Nuclear Information System (INIS)

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  10. Interaction of antimicrobial peptides with lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Hanulova, Maria

    2008-12-15

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  11. Peptide-membrane interactions of arginine-tryptophan peptides probed using quartz crystal microbalance with dissipation monitoring.

    KAUST Repository

    Rydberg, Hanna A

    2014-04-18

    Membrane-active peptides include peptides that can cross cellular membranes and deliver macromolecular cargo as well as peptides that inhibit bacterial growth. Some of these peptides can act as both transporters and antibacterial agents. It is desirable to combine the knowledge from these two different fields of membrane-active peptides into design of new peptides with tailored actions, as transporters of cargo or as antibacterial substances, targeting specific membranes. We have previously shown that the position of the amino acid tryptophan in the peptide sequence of three arginine-tryptophan peptides affects their uptake and intracellular localization in live mammalian cells, as well as their ability to inhibit bacterial growth. Here, we use quartz crystal microbalance with dissipation monitoring to assess the induced changes caused by binding of the three peptides to supported model membranes composed of POPC, POPC/POPG, POPC/POPG/cholesterol or POPC/lactosyl PE. Our results indicate that the tryptophan position in the peptide sequence affects the way these peptides interact with the different model membranes and that the presence of cholesterol in particular seems to affect the membrane interaction of the peptide with an even distribution of tryptophans in the peptide sequence. These results give mechanistic insight into the function of these peptides and may aid in the design of membrane-active peptides with specified cellular targets and actions.

  12. Urodilatin. A renal natriuretic peptide

    International Nuclear Information System (INIS)

    Development and validation of a radioimmunoassay for endogenous URO in urine and synthetic URO in plasma is described. The first obstacle to overcome was to produce an antibody specific for URO. A polyclonal URO antibody with a cross-reactivity with the structural highly homologous atrial natriuretic peptide (ANP) was developed by immunization of rabbits with the whole URO(95-126). Purification of the polyclonal URO antiserum with CNBr-activated Sepharose affinity chromatography was a simple way of producing a URO-specific antibody without cross-reactivity with ANP analogues. A reliable 125I-labelled URO tracer was made with the Iodo-Gen method. Prior to the assay, the urine samples were prepared by ethanol with a recovery of unlabelled URO between 80 - 100% and the plasma samples were Sep-Pak C18 extracted with a recovery of about 50%. The radioimmunoassay is performed in 3 days, using polyethylene glycol for separation. The sensitivity of the assay was improved by sample preparation and concentration, reducing the amount of tracer and late addition, reducing the amount of antibody and increasing the incubation time and lowering the temperature of incubation. The infusion rate of 20 ng URO kg-1 min-1 was most potential and well tolerated in healthy subjects. The short-term natriuretic and diuretic effects were closely associated with a significant diminished sodium reabsorption in the distal nephron. Further studies are needed to exploit the therapeutical potential of URO, for example in patients with sodium-water retaining disorders. The therapeutical dose range will probably be narrow due to the blood pressure lowering effect of URO with infusion rates higher than 20-30 ng kg-1 min-1. (EHS)

  13. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Dimitris Missirlis

    Full Text Available BACKGROUND: Peptide amphiphiles (PAs are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. METHODOLOGY/PRINCIPAL FINDINGS: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. CONCLUSIONS/SIGNIFICANCE: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  14. Peptide segment ligation:A new method for synthesis of peptide and protein

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ The protein structure-function relationships are always highlighted in the field of life science. Protein synthesis from genomic sequence data is gaining significance in the "post-genomic era" of biomedical research by providing direct access to functional proteins. The manually or automatically stepwise solid phase peptide synthesis (SPPS) allows peptide of up to 60 residues to be routinely constructed in good yield and high purity[1,2]. The assembly of longer proteins via the gene engineering technology (e.g. recombinant DNA-based molecular biology or site- directed mutagenesis) and convergent peptide synthesis are necessary. Although the current biosynthetic method allows unnatural amino acids to be incorporated into proteins or peptides[3], only ?-peptide in the protein backbone can be obtained. A lot of problems associated with the classic convergent peptide synthesis approach, such as the poor solubility, inadequate purification techniques, and limited characterization methods with the fully protected segment[6]. However, totally chemical synthetic method can easily obtain ?- or ?-peptide[4] and even branch peptide[5].

  15. Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity

    DEFF Research Database (Denmark)

    Harndahl, Mikkel Nors; Rasmussen, Michael; Nielsen, Morten;

    2012-01-01

    Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity Mikkel Harndahla, Michael Rasmussena, Morten Nielsenb, Soren Buusa,∗ a Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Denmark b Center for Biological Seq...... al., 2007. J. Immunol. 178, 7890–7901. doi:10.1016/j.molimm.2012.02.025...

  16. Clinical relevance of intestinal peptide uptake

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2015-01-01

    AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature articles sourced through Pub Med related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed.Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition,abstracted information translated to English in Pub Med was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.RESULTS: Assimilation of dietary protein in humans involves gastric and pancreatic enzyme hydrolysis to luminal oligopeptides and free amino acids. During the ensuing intestinal phase, these hydrolytic products are transported into the epithelial cell and, eventually, the portal vein. A critical component of this process is the uptake of intact di-peptides and tri-peptides by an independent Pep T1. A number of "peptide-mimetic" pharmaceutical agents may also be transported through this carrier, important for uptake of different antibiotics, antiviral agents and angiotensin-converting enzyme inhibitors. In addition, specific peptide products of intestinal bacteria may also be transported by Pep T1, with initiation and persistence of an immune response including increased cytokine production and associated intestinal inflammatory changes. Interestingly, these inflammatory changes may also be attenuated with orallyadministered anti-inflammatory tripeptides administered as site-specific nanoparticles and taken up by this Pep T1 transport protein. CONCLUSION: Further evaluation of the role of this transporter in treatment of

  17. New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

    DEFF Research Database (Denmark)

    Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen;

    2002-01-01

    the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wave-numbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups...... between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which...... on the dendrimer host. The influence of side-chain motif on interactions with the host is analyzed by using seven different N-Boc-protected tripeptides as guests for the dendrimer, Downfield shifts of up to 1.3 ppm were observed for the guest amide NH-proton signals. These shifts decrease with increasing...

  18. A peptide & peptide nucleic acid synthesis technology for transporter molecules and theranostics--the SPPS.

    Science.gov (United States)

    Pipkorn, Ruediger; Braun, Klaus; Wiessler, Manfred; Waldeck, Waldemar; Schrenk, Hans-Hermann; Koch, Mario; Semmler, Wolfhard; Komljenovic, Dorde

    2014-01-01

    Advances in imaging diagnostics using magnetic resonance tomography (MRT), positron emission tomography (PET) and fluorescence imaging including near infrared (NIR) imaging methods are facilitated by constant improvement of the concepts of peptide synthesis. Feasible patient-specific theranostic platforms in the personalized medicine are particularly dependent on efficient and clinically applicable peptide constructs. The role of peptides in the interrelations between the structure and function of proteins is widely investigated, especially by using computer-assisted methods. Nowadays the solid phase synthesis (SPPS) chemistry emerges as a key technology and is considered as a promising methodology to design peptides for the investigation of molecular pharmacological processes at the transcriptional level. SPPS syntheses could be carried out in core facilities producing peptides for large-scale scientific implementations as presented here. PMID:24843319

  19. A Peptide & Peptide Nucleic Acid Synthesis Technology for Transporter Molecules and Theranostics - The SPPS

    Science.gov (United States)

    Pipkorn, Ruediger; Braun, Klaus; Wiessler, Manfred; Waldeck, Waldemar; Schrenk, Hans-Hermann; Koch, Mario; Semmler, Wolfhard; Komljenovic, Dorde

    2014-01-01

    Advances in imaging diagnostics using magnetic resonance tomography (MRT), positron emission tomography (PET) and fluorescence imaging including near infrared (NIR) imaging methods are facilitated by constant improvement of the concepts of peptide synthesis. Feasible patient-specific theranostic platforms in the personalized medicine are particularly dependent on efficient and clinically applicable peptide constructs. The role of peptides in the interrelations between the structure and function of proteins is widely investigated, especially by using computer-assisted methods. Nowadays the solid phase synthesis (SPPS) chemistry emerges as a key technology and is considered as a promising methodology to design peptides for the investigation of molecular pharmacological processes at the transcriptional level. SPPS syntheses could be carried out in core facilities producing peptides for large-scale scientific implementations as presented here. PMID:24843319

  20. Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity.

    Science.gov (United States)

    Auvynet, Constance; Rosenstein, Yvonne

    2009-11-01

    The term 'antimicrobial peptides' refers to a large number of peptides first characterized on the basis of their antibiotic and antifungal activities. In addition to their role as endogenous antibiotics, antimicrobial peptides, also called host defense peptides, participate in multiple aspects of immunity (inflammation, wound repair, and regulation of the adaptive immune system) as well as in maintaining homeostasis. The possibility of utilizing these multifunctional molecules to effectively combat the ever-growing group of antibiotic-resistant pathogens has intensified research aimed at improving their antibiotic activity and therapeutic potential, without the burden of an exacerbated inflammatory response, but conserving their immunomodulatory potential. In this minireview, we focus on the contribution of small cationic antimicrobial peptides - particularly human cathelicidins and defensins - to the immune response and disease, highlighting recent advances in our understanding of the roles of these multifunctional molecules.

  1. Urinary Peptide Levels in Patients with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Mungli Prakash

    2010-10-01

    Full Text Available Introduction: Peptide levels in urine are found to be decreased in renal failure. In the current study urinary peptide levels were determined in chronic renal failure (CRF patients. Method: 86 CRF patients and 80 healthy controls were selected for the study. Urinary proteins and peptide levels were determined by spectrophotometer based Lowry and Bradford methods. Urinary creatinine levels were determined by clinical chemistry analyzer. Results: There was significant decrease in urinary peptide levels in CRF patients and Urinary % peptides were significantly decreased in CRF patients as compared to healthy controls. Urinary % peptides correlated negatively with proteinuria. Conclusion: we have found decrease in urinary peptides and % urinary peptides in CRF patients and possibly measurement of % urinary peptides may possibly serve as better indicator in early detection of impairment in renal function.

  2. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  3. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    Energy Technology Data Exchange (ETDEWEB)

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)

    2011-09-16

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  4. Glucagon-Like Peptide-1 Gene Therapy

    Directory of Open Access Journals (Sweden)

    Anne M. Rowzee

    2011-01-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 is a small peptide component of the prohormone, proglucagon, that is produced in the gut. Exendin-4, a GLP-1 receptor agonist originally isolated from the saliva of H. suspectum or Gila monster, is a peptide that shares sequence and functional homology with GLP-1. Both peptides have been demonstrated to stimulate insulin secretion, inhibit glucagon secretion, promote satiety and slow gastric emptying. As such, GLP-1 and Exendin-4 have become attractive pharmaceutical targets as an adjunctive therapy for individuals with type II diabetes mellitus, with several products currently available clinically. Herein we summarize the cell biology leading to GLP-1 production and secretion from intestinal L-cells and the endocrine functions of this peptide and Exendin-4 in humans. Additionally, gene therapeutic applications of GLP-1 and Exendin-4 are discussed with a focus on recent work using the salivary gland as a gene therapy target organ for the treatment of diabetes mellitus.

  5. Biosynthetic engineering of nonribosomal peptide synthetases.

    Science.gov (United States)

    Kries, Hajo

    2016-09-01

    From the evolutionary melting pot of natural product synthetase genes, microorganisms elicit antibiotics, communication tools, and iron scavengers. Chemical biologists manipulate these genes to recreate similarly diverse and potent biological activities not on evolutionary time scales but within months. Enzyme engineering has progressed considerably in recent years and offers new screening, modelling, and design tools for natural product designers. Here, recent advances in enzyme engineering and their application to nonribosomal peptide synthetases are reviewed. Among the nonribosomal peptides that have been subjected to biosynthetic engineering are the antibiotics daptomycin, calcium-dependent antibiotic, and gramicidin S. With these peptides, incorporation of unnatural building blocks and modulation of bioactivities via various structural modifications have been successfully demonstrated. Natural product engineering on the biosynthetic level is not a reliable method yet. However, progress in the understanding and manipulation of biosynthetic pathways may enable the routine production of optimized peptide drugs in the near future. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27465074

  6. Preparation of Soy Peptides by Liquid Fermentation

    Institute of Scientific and Technical Information of China (English)

    LiLi; YangXiaoqun; ZhaoMouming; LiangShizhong

    2002-01-01

    Many kinds of microorganism can produce a mount of protease which subsequently hydrolysis the protein of the medium into peptides when they grow in protein containing liquid medium.In the present investigation,the conditions of preparing soybean peptides by liquid fermentation were studied,following results were obtained:(1)SPI is a nice nitrogen source and meanwhile an inducible factor of protease production;its concentration can be as high as 3%-4%.(2)Sucrose is the best carbon source;its concentration is 1%-4%.(3)Under the conditions of 28℃,initial pH6.0,inoculum size 4%,cell age 36hr and fermentation time 24hr-30hr,we can obtain soybean peptides or fermentation liquor with good flavor,its DH reaches 25%-30% and the yield rate can be as high as 75%.(4)Mass spectrograph indicate the MW of the fermentation liquid or the soybean peptides mainly distribute at about 4000Dal,these imply a promising prospect of industrial application of submerged fermentation in producing soybean peptides.

  7. Antimicrobial Peptides in Innate Immunity against Mycobacteria.

    Science.gov (United States)

    Shin, Dong-Min; Jo, Eun-Kyeong

    2011-10-01

    Antimicrobial peptides/proteins are ancient and naturallyoccurring antibiotics in innate immune responses in a variety of organisms. Additionally, these peptides have been recognized as important signaling molecules in regulation of both innate and adaptive immunity. During mycobacterial infection, antimicrobial peptides including cathelicidin, defensin, and hepcidin have antimicrobial activities against mycobacteria, making them promising candidates for future drug development. Additionally, antimicrobial peptides act as immunomodulators in infectious and inflammatory conditions. Multiple crucial functions of cathelicidins in antimycobacterial immune defense have been characterized not only in terms of direct killing of mycobacteria but also as innate immune regulators, i.e., in secretion of cytokines and chemokines, and mediating autophagy activation. Defensin families are also important during mycobacterial infection and contribute to antimycobacterial defense and inhibition of mycobacterial growth both in vitro and in vivo. Hepcidin, although its role in mycobacterial infection has not yet been characterized, exerts antimycobacterial effects in activated macrophages. The present review focuses on recent efforts to elucidate the roles of host defense peptides in innate immunity to mycobacteria.

  8. Peptide friction in water nanofilm on mica surface

    Institute of Scientific and Technical Information of China (English)

    Zhou Bo; Xiu Peng; Wang Chun-Lei; Fang Hai-Ping

    2012-01-01

    Peptide frictions in water nanofilms of various thicknesses on a mica surface are studied via molecular dynamics simulations.We find that the forced lateral motion of the peptide exhibits stick-slip behaviour at low water coverage;in contrast,the smooth gliding motion is observed at higher water coverage.The adsorbed peptide can form direct peptide-surface hydrogen bonds as well as indirect peptide-water-surface hydrogen bonds with the substrate. We propose that the stick-slip phenomenon is attributed to the overall effects of direct and indirect hydrogen bonds formed between the surface and the peptide.

  9. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

    International Nuclear Information System (INIS)

    The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

  10. Anisotropic Membrane Curvature Sensing by Amphipathic Peptides.

    Science.gov (United States)

    Gómez-Llobregat, Jordi; Elías-Wolff, Federico; Lindén, Martin

    2016-01-01

    Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodeling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe an approach to study curvature sensing by simulating the interactions of single molecules with a buckled lipid bilayer. We analyze three amphipathic antimicrobial peptides, a class of membrane-associated molecules that specifically target and destabilize bacterial membranes, and find qualitatively different sensing characteristics that would be difficult to resolve with other methods. Our findings provide evidence for direction-dependent curvature sensing mechanisms in amphipathic peptides and challenge existing theories of hydrophobic insertion. The buckling approach is generally applicable to a wide range of curvature-sensing molecules, and our results provide strong motivation to develop new experimental methods to track position and orientation of membrane proteins. PMID:26745422

  11. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    Energy Technology Data Exchange (ETDEWEB)

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays

  12. Spider-Venom Peptides as Therapeutics

    Directory of Open Access Journals (Sweden)

    Glenn F. King

    2010-12-01

    Full Text Available Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction.

  13. Amyloid fibrils compared to peptide nanotubes.

    Science.gov (United States)

    Zganec, Matjaž; Zerovnik, Eva

    2014-09-01

    Prefibrillar oligomeric states and amyloid fibrils of amyloid-forming proteins qualify as nanoparticles. We aim to predict what biophysical and biochemical properties they could share in common with better researched peptide nanotubes. We first describe what is known of amyloid fibrils and prefibrillar aggregates (oligomers and protofibrils): their structure, mechanisms of formation and putative mechanism of cytotoxicity. In distinction from other neuronal fibrillar constituents, amyloid fibrils are believed to cause pathology, however, some can also be functional. Second, we give a review of known biophysical properties of peptide nanotubes. Finally, we compare properties of these two macromolecular states side by side and discuss which measurements that have already been done with peptide nanotubes could be done with amyloid fibrils as well.

  14. Anisotropic membrane curvature sensing by antibacterial peptides

    CERN Document Server

    Gómez-Llobregat, Jordi; Lindén, Martin

    2014-01-01

    Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodeling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe a new approach to study curvature sensing, by simulating the direction-dependent interactions of single molecules with a buckled lipid bilayer. We analyze three antimicrobial peptides, a class of membrane-associated molecules that specifically target and destabilize bacterial membranes, and find qualitatively different sensing characteristics that would be difficult to resolve with other methods. These findings provide new insights into the microscopic mechanisms of antimicrobial peptides, which might aid the development of new antibiotics. Our approach is generally applicable to a wide range of curvature sensing molecules, and our results provide strong motivation to develop new experimental methods to track position and orientation of membrane p...

  15. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  16. Preparation of Soy Peptides by Liquid Fermentation

    Institute of Scientific and Technical Information of China (English)

    Li Li; Yang Xiaoqun; Zhao Mouming; Liang Shizhong

    2002-01-01

    Many kinds of microorganism canproduce a mount of protease which subsequentlyhydrolysis the protein of the medium into peptideswhen they grow in protein containing liquidmedium. In the present investigation, theconditions of preparing soybean peptides byliquid fermentation were studied following resultswere obtained: (1) SPI is a nice nitrogen sourceand meanwhile an inducible factor of proteaseproduction; its concentration can be as high as3%-4%. (2) Sucrose is the best carbon source;its concentration is 1%-4%. (3) Under theconditions of 28℃, initial pH 60, inoculum size4%, cell age 36hr and fermentation time 24hr-30hr, we can obtain soybean peptides orfermentation liquor with good flavor, its Dhreaches 25%-30% and the yield rate can be ashigh as 75%. (4) Mass spectrograph indicate theMW of the fermentation liquid or the soybeanpeptides mainly distribute at a Dal, theseimply a promising prospect of industrialapplication of submerged fermentation inproducing soybean peptides.

  17. Antimicrobial Peptides: Multifunctional Drugs for Different Applications

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2012-02-01

    Full Text Available Antimicrobial peptides (APs are an important part of the innate immune system in epithelial and non-epithelial surfaces. So far, many different antimicrobial peptides from various families have been discovered in non-vertebrates and vertebrates. They are characterized by antibiotic, antifungal and antiviral activities against a variety of microorganisms. In addition to their role as endogenous antimicrobials, APs participate in multiple aspects of immunity. They are involved in septic and non-septic inflammation, wound repair, angiogenesis, regulation of the adaptive immune system and in maintaining homeostasis. Due to those characteristics AP could play an important role in many practical applications. Limited therapeutic efficiency of current antimicrobial agents and the emerging resistance of pathogens require alternate antimicrobial drugs. The purpose of this review is to highlight recent literature on functions and mechanisms of APs. It also shows their current practical applications as peptide therapeutics and bioactive polymers and discusses the possibilities of future clinical developments.

  18. Antimicrobial peptides in innate immune responses.

    Science.gov (United States)

    Sørensen, Ole E; Borregaard, Niels; Cole, Alexander M

    2008-01-01

    Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain diseases like Crohn's disease and atopic dermatitis. AMPs are attractive candidates for development of novel antibiotics due to their in vivo activity profile and some peptides may serve as templates for further drug development.

  19. Antimicrobial peptides in innate immune responses

    DEFF Research Database (Denmark)

    Sorensen, O.E.; Borregaard, N.; Cole, A.M.

    2008-01-01

    Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de...... novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain...... diseases like Crohn's disease and atopic dermatitis. AMPs are attractive candidates for development of novel antibiotics due to their in vivo activity profile and some peptides may serve as templates for further drug development Udgivelsesdato: 2008...

  20. Interactions at the Peptide/Silicon Surfaces: Evidence of Peptide Multilayer Assembly.

    Science.gov (United States)

    Pápa, Zsuzsanna; Ramakrishnan, Sathish Kumar; Martin, Marta; Cloitre, Thierry; Zimányi, László; Márquez, Jessica; Budai, Judit; Tóth, Zsolt; Gergely, Csilla

    2016-07-19

    Selective deposition of peptides from liquid solutions to n- and p-doped silicon has been demonstrated. The selectivity is governed by peptide/silicon adhesion differences. A noninvasive, fast characterization of the obtained peptide layers is required to promote their application for interfacing silicon-based devices with biological material. In this study we show that spectroscopic ellipsometry-a method increasingly used for the investigation of biointerfaces-can provide essential information about the amount of adsorbed peptide material and the degree of coverage on silicon surfaces. We observed the formation of peptide multilayers for a strongly binding adhesion peptide on p-doped silicon. Application of the patterned layer ellipsometric evaluation method combined with Sellmeier dispersion led to physically consistent results, which describe well the optical properties of peptide layers in the visible spectral range. This evaluation allowed the estimation of surface coverage, which is an important indicator of adsorption quality. The ellipsometric findings were well supported by atomic force microscopy results. PMID:27315212

  1. Aerosolized Medications for Gene and Peptide Therapy.

    Science.gov (United States)

    Laube, Beth L

    2015-06-01

    Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for

  2. Selection of trkB-binding peptides from a phage-displayed random peptide library

    Institute of Scientific and Technical Information of China (English)

    MA; Zhongcai; (马仲才); WU; Xiaolan; (吴晓兰); CAO; Mingmei; (曹明媚); PAN; Wei; (潘; 卫); ZHU; Fenlu; (朱分禄); CHEN; Jingshan; (陈景山); QI; Zhongtian; (戚中田)

    2003-01-01

    Brain-derived neurotrophic factor (BDNF) shows potential in the treatment of neurodegenerative diseases, but the therapeutic application of BDNF has been greatly limited because it is too large in molecular size to permeate blood-brain barrier. To develop low-molecular-weight BDNF-like peptides, we selected a phage-displayed random peptide library using trkB expressed on NIH 3T3 cells as target in the study. With the strategy of peptide library incubation with NIH 3T3 cells and competitive elution with 1 υg/mL of BDNF in the last round of selection, the specific phages able to bind to the natural conformation of trkB and antagonize BDNF binding to trkB were enriched effectively. Five trkB-binding peptides were obtained, in which a core sequence of CRA/TXφXXφXXC (X represents the random amino acids, φ represents T, L or I) was identified. The BDNF-like activity of these five peptides displayed on phages was not observed, though all of them antagonized the activity of BDNF in a dose-dependent manner. Similar results were obtained with the synthetic peptide of C1 clone, indicating that the 5 phage-derived peptides were trkB antagonists. These low-molecular-weight antagonists of trkB may be of potential application in the treatment of neuroblastoma and chronic pain. Meanwhile, the obtained core sequence also could be used as the base to construct the secondary phage-displayed peptide library for further development of small peptides mimicking BDNF activity.

  3. Peptoid-Peptide hybrid backbone architectures

    DEFF Research Database (Denmark)

    Olsen, Christian Adam

    2010-01-01

    -amino acids (alpha/beta-peptides) have been investigated in some detail as well. The present Minireview is a survey of the literature concerning hybrid structures of alpha-amino acids and peptoids, including beta-peptoids (N-alkyl-beta-alanine oligomers), and is intended to give an overview of this area......Peptidomimetic oligomers and foldamers have received considerable attention for over a decade, with beta-peptides and the so-called peptoids (N-alkylglycine oligomers) representing prominent examples of such architectures. Lately, hybrid or mixed backbones consisting of both alpha- and beta...

  4. The Dicyclopropylmethyl (Dcpm) Peptide Backbone Protectant†

    Science.gov (United States)

    Carpino, Louis A.; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-01-01

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106–126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit. PMID:19719204

  5. Dissecting and Exploiting Nonribosomal Peptide Synthetases

    Institute of Scientific and Technical Information of China (English)

    Qing-Tao SHEN; Xiu-Lan CHEN; Cai-Yun SUN; Yu-Zhong ZHANG

    2004-01-01

    A large number of therapeutically useful cyclic and linear peptides of bacteria or fungal origin are synthesized via a template-directed, nucleic-acid-independent nonribosomal mechanism. This process is carried out by mega-enzymes called nonribosomal peptide synthetases (NRPSs). NRPSs contain repeated coordinated groups of active sites called modules, and each module is composed of several domains with different catalytic activities. The familiarity to these domains lays base for the future genetic engineering of NRPSs to generate entirely "unnature" Products. The details about NRPSs domain structures and the exploitation of NRPSs are described in this review.

  6. Minimizing acylation of peptides in PLGA microspheres

    OpenAIRE

    Zhang, Ying; Schwendeman, Steven P.

    2012-01-01

    The main objective of this study was to characterize and find mechanisms to prevent acylation of therapeutic peptides encapsulated in glucose-star poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. The effect of addition of divalent cation salts CaCl2, MnCl2 as well as carboxymethyl chitosan (CMCS) on inhibition of acylation of octreotide (Oct), salmon calcitonin (sCT), and human parathyroid hormone (hPTH) was evaluated. Peptide content and integrity inside the degrading microspheres was ...

  7. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    This thesis describes the design and synthesis of peptide-based serine protease inhibitors. The targeted protease, urokinase-type plasminogen activator (uPA) activates plasminogen, which plays a major role in cancer metastasis. The peptide upain-2 (S 1 ,S 12-cyclo-AcCSWRGLENHAAC-NH2) is a highly...... increased. Finally, the effect of multivalent display of upain-2 was investigated. Several dimers of upain-2 were made and the attachment of upain-2 via the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) onto an alkyne functionalized carbohydrate scaffold was investigated. Besides the synthesis...

  8. Radioimmunoassay for C-peptide and proinsulin

    International Nuclear Information System (INIS)

    Proinsulin, the biosynthetic precursor of insulin, was discovered by Steiner et al. (1967) and shown to be converted to insulin and C-peptide in the β-cell. The first part of this paper deals with aspects of the radioimmunoassay for C-peptide with special emphasis on the development and the sources of errors encountered in our laboratory (Heding, 1975; Naithani et al., 1975). The second part deals with the many problems involved in the determination of human proinsulin and describes a direct and specific radioimmunoassay developed for measuring proinsulin in serum with a detection limit of less than 0.01 pmol/ml. (Auth.)

  9. Activity of Cathelicidin Peptides against Simkania negevensis

    Directory of Open Access Journals (Sweden)

    Manuela Donati

    2011-01-01

    Full Text Available The in vitro activity of six cathelicidin peptides against the reference strain Z of Simkania negevensis was investigated. Five peptides—PG-1, Bac7, SMAP-29, BMAP-27, and BMAP-28—proved to be active at very low concentrations (1 to 0.1 μg/mL, while LL-37 cathelicidin was ineffective even at a concentration of 100 μg/mL. In comparison to chlamydiae, S. negevensis proved to be more susceptible to the antimicrobial peptides tested.

  10. Glucagon-like peptides 1 and 2

    DEFF Research Database (Denmark)

    Kissow, Hannelouise

    2015-01-01

    -effects. RECENT FINDINGS: The intestinal glucagon-like peptide-2 (GLP-2) is secreted from the intestinal endocrine L cells after nutrient intake, but recent findings show that the peptide concentration in the plasma also rises after intestinal injury and that GLP-2 receptor activation is crucial for intestinal...... for therapeutic use. In type 2 diabetic and obese patients, GLP secretion is impaired. Elucidating the role of these endogenous hormones could lead to the identification of mucositis risk factors and an alternative preventive therapy for these patients....

  11. Neuropeptides and Peptide Hormones in Anopheles gambiae

    Science.gov (United States)

    Riehle, Michael A.; Garczynski, Stephen F.; Crim, Joe W.; Hill, Catherine A.; Brown, Mark R.

    2002-10-01

    The African malaria mosquito, Anopheles gambiae, is specialized for rapid completion of development and reproduction. A vertebrate blood meal is required for egg production, and multiple feedings subsequently allow transmission of malaria parasites, Plasmodium spp. Regulatory peptides from 35 genes annotated from the A. gambiae genome likely coordinate these and other physiological processes. Plasmodium parasites may affect actions of newly identified insulin-like peptides, which coordinate growth and reproduction of its vector, A. gambiae, as in Drosophila melanogaster, Caenorhabditis elegans, and mammals. This genomic information provides a basis to expand understanding of hematophagy and pathogen transmission in this mosquito.

  12. [Antimicrobial peptide in dentisty. Literature review].

    Science.gov (United States)

    Sato, F Simain; Rompen, E; Heinen, E

    2009-12-01

    The use of antimicrobial substances has contributed to the development of multiple antimicrobial resistances (1), challenging the pharmaceutical industry to develop with new, innovative, and effective molecules. Discovered around 1980, molecules called natural antimicrobial peptides (AMPs) appear to hold great potential for the treatment of infections. These cationic peptides are able to stop the bacterial development and to control infections. The purpose of this review is to help improve the understanding of the way AMPs operate in the context of the development of new cures against viruses, bacteria, and mushrooms found in the human body in general and in the oral cavity in particular. PMID:20143750

  13. Calcitonin gene-related peptide (CGRP), peptide YY (PYY) gastrin releasing peptide (GRP) and others in hamster lung and plasma

    International Nuclear Information System (INIS)

    Rabbit antisera to CGRP, PYY, neuropeptide Y (NPY) and GRP were used for immunocytochemical localization of these peptides in lungs of neonate hamsters at birth and 6 d of age and young (70 gm) and adult (107 gm) hamsters. The peroxidase-antiperoxidase method was applied to paraffin sections of tissue fixed in Bouin's or Zamboni's solution. Furthermore, radioimmunoassay (RIA) was used to quantify these peptides in lung tissue and plasma from the young hamsters (n=13). Distinct CGRP-like immunoreactivity (IR) was noted in grouped (NEB) and individual (NEC) neuroendocrine cells at all ages including all airways from trachea (NECs only) to alveoli. In some NEBs this IR coexisted with 5-HT-like IR. PYY- and NPY-like Ir was mainly noted in NEBs and NECs at the level of bronchioles and alveoli, and weak GRP-like IR was present in neuroendocrine-like cells of small airways. Measurable quantities of all peptides were recorded by RIA. Females had higher lung and plasma levels of CGRP and plasma levels of PYY than males and tended to have higher lung levels of GRP. The neuropeptides CGRP, PYY and the analog NPY are putative regulators of local pulmonary blood flow by vasodilation (CGRP) and constriction (PYY, NPY), and GRP is known to regulate peptide release

  14. Current trends in the clinical development of peptide therapeutics.

    Science.gov (United States)

    Saladin, Pauline M; Zhang, Bodi D; Reichert, Janice M

    2009-12-01

    The development of peptides as drugs is attracting increasing attention from the pharmaceutical industry. This interest is at least partially a consequence of the widespread acceptance of therapeutic proteins by physicians and patients, and because of improvements to problems such as a short half-life and delivery issues. The markets for peptide-based compounds can be substantial, with six peptide drugs attaining global sales of more than US $750 million in 2008. To track trends in the clinical development and marketing approval of peptides, Tufts Center for the Study of Drug Development and Ferring Research Institute compiled publically available data for peptides that entered clinical trials sponsored by commercial firms, with a focus on peptide therapeutics, but also including peptide vaccines and diagnostics. The results provide an historical overview of the development of peptide therapeutics, and may inform strategic planning in this area.

  15. A peptide antagonist disrupts NK cell inhibitory synapse formation.

    Science.gov (United States)

    Borhis, Gwenoline; Ahmed, Parvin S; Mbiribindi, Bérénice; Naiyer, Mohammed M; Davis, Daniel M; Purbhoo, Marco A; Khakoo, Salim I

    2013-03-15

    Productive engagement of MHC class I by inhibitory NK cell receptors depends on the peptide bound by the MHC class I molecule. Peptide:MHC complexes that bind weakly to killer cell Ig-like receptors (KIRs) can antagonize the inhibition mediated by high-affinity peptide:MHC complexes and cause NK cell activation. We show that low-affinity peptide:MHC complexes stall inhibitory signaling at the step of Src homology protein tyrosine phosphatase 1 recruitment and do not go on to form the KIR microclusters induced by high-affinity peptide:MHC, which are associated with Vav dephosphorylation and downstream signaling. Furthermore, the low-affinity peptide:MHC complexes prevented the formation of KIR microclusters by high-affinity peptide:MHC. Thus, peptide antagonism of NK cells is an active phenomenon of inhibitory synapse disruption.

  16. Evaluation of MAP-specific peptides following vaccination of goats

    DEFF Research Database (Denmark)

    Lybeck, Kari; Sjurseth, Siri K.; Melvang, Heidi Mikkelsen;

    Our aim is to develop a subunit MAP vaccine not interfering with the diagnosis of paratuberculosis or bovine tuberculosis. This study’s objective was to evaluate MAP-specific peptides defined by in silico analysis. Peptides were picked by 1) comparing MAP genomes to that of other mycobacterium...... species or 2) selected based on “experience”. Peptides predicted to bind bovine MHC II by in silico analysis were included in further studies, resulting in two panels 1) genome-based and 2) selected. Initially, two groups of 15 healthy goats were vaccinated with one of the two panels (50 µg/peptide in CAF......01 adjuvant/CAF04 for boosting). Four MAP-infected goats were also vaccinated. In a second vaccination trail, groups of 8 healthy goat kids were vaccinated with genome-based peptides, selected peptides or selected peptides linked together in a recombinant protein (20 µg/peptide or 50 µg protein...

  17. Self-Assembly and Hydrogelation of Peptide Amphiphiles

    Directory of Open Access Journals (Sweden)

    Wahyudi Priyono Suwarso

    2012-04-01

    Full Text Available Seven peptide amphiphiles were successfully synthesized using solid phase peptide synthesis method. Peptide amphiphiles were characterized using matrix assisted laser desorption/ionization (MALDI. Atomic force microscopy (AFM study showed that peptide amphiphiles having glycine, valine, or proline as linker, self-assembled into 100-200 nm nanofibers structure. According to our research, both peptide amphiphile with positive and negative charges bear similar self-assembly properties. Peptide amphiphile also showed its capability as low molecular weight gelator (LMWG. Peptide amphiphiles bearing C-16 and C-12 as alkyl showed better hydrogelation properties than C-8 alkyl. Five out of seven peptide amphiphiles have minimum gelation concentration (MGC lower than 1% (w/v.

  18. B-type natriuretic peptide secretion following scuba diving

    DEFF Research Database (Denmark)

    Passino, Claudio; Franzino, Enrico; Giannoni, Alberto;

    2011-01-01

    To examine the neurohormonal effects of a scuba dive, focusing on the acute changes in the plasma concentrations of the different peptide fragments from the B-type natriuretic peptide (BNP) precursor....

  19. Cancer Treatment Using Peptides: Current Therapies and Future Prospects

    OpenAIRE

    Jyothi Thundimadathil

    2012-01-01

    This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to convent...

  20. A Newcomer’s Guide to Peptide Crystallography

    OpenAIRE

    Spencer, Ryan K.; Nowick, James S.

    2015-01-01

    Here we provide a guide for adapting the tools developed for protein X-ray crystallography to study the structures and supramolecular assembly of peptides. Peptide crystallography involves selecting a suitable peptide, crystallizing the peptide, collecting X-ray diffraction data, processing the diffraction data, determining the crystallographic phases and generating an electron density map, building and refining models, and depositing the crystallographic structure in the Protein Data Bank (P...

  1. Atrial secretion of B-type natriuretic peptide

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Friis-Hansen, Lennart; Rehfeld, Jens F;

    2006-01-01

    In the normal heart, the endocrine capacity resides in the atria. Atrial myocytes express and secrete natriuretic hormones that regulate fluid homeostasis and blood pressure. But in ventricular disease, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression is also...... activated in ventricular myocytes. Plasma concentrations of natriuretic peptides and their biosynthetic precursors are accordingly increased in patients with marked ventricular dysfunction. In contrast, atrial peptide secretion in ventricular disease has received less attention, and our present...

  2. Post-Translational Modifications in Secreted Peptide Hormones in Plants

    OpenAIRE

    Matsubayashi, Yoshikatsu

    2010-01-01

    More than a dozen secreted peptides are now recognized as important hormones that coordinate and specify cellular functions in plants. Recent evidence has shown that secreted peptide hormones often undergo post-translational modification and proteolytic processing, which are critical for their function. Such ‘small post-translationally modified peptide hormones’ constitute one of the largest groups of peptide hormones in plants. This short review highlights recent progress in research on post...

  3. Targeting and Therapeutic Peptides in Nanomedicine for Atherosclerosis

    OpenAIRE

    Chung, Eun Ji

    2016-01-01

    Peptides in atherosclerosis nanomedicine provide structural, targeting, and therapeutic functionality, and can assist in overcoming delivery barriers of traditional pharmaceuticals. Moreover, their inherent biocompatibility and biodegradability make them especially attractive as materials intended for use in vivo. In this review, an overview of nanoparticle-associated targeting and therapeutic peptides for atherosclerosis are provided, including peptides designed for cellular targets such as ...

  4. Antimicrobial activity of human salivary mucin-derived peptides

    NARCIS (Netherlands)

    Wei, G.

    2008-01-01

    We investigated: a) relationships between molecular properties and antimicrobial functions of MUC7 peptides, b) effects of host physiological factors on the antimicrobial activity of MUC7 peptides, c) enhancement of antifungal activity by combination of MUC7 peptides with EDTA or other agents, d) an

  5. Nanostructure formation enhances the activity of LPS-neutralizing peptides.

    NARCIS (Netherlands)

    Mas-Moruno, C.; Cascales, L.; Cruz, L.J.; Mora, P.; Perez-Paya, E.; Albericio, F.

    2008-01-01

    Peptides that interact with lipopolysaccharide (LPS) can provide the basis for the development of new antisepsis agents. In this work, several LPS-neutralizing acyl peptides derived from LALF, BPI, and SAP were prepared, structurally characterized, and biologically evaluated. In all cases, peptides

  6. Synthetic Peptide libraries for T-cell epitope identification.

    Science.gov (United States)

    Hiemstra, H S; Drijfhout, J W; Koning, F

    2000-01-01

    This chapter describes a methodology for elucidating immunogenic epitopes stimulatory for CD4(+) T-cell clones (Fig. 1). The methodology makes use of synthetic peptide libraries and must be regarded as an alternative to other approaches, such as peptide elution or the application of genetic libraries. The methodology only requires knowledge about the restriction element of the T-cell clone. The restriction element determines which major histocompatibility complex (MHC)-binding anchor motif must be built into the library peptides. A synthetic peptide library is prepared comprising approx 8 million peptides. The synthesis proceeds via a mix-and-split protocol using a solidphase approach on a hybrid resin (1,2). On a hybrid resin, most of the peptide material (84%) is attached via an acid-labile linker whereas the remaining part of the peptide material is acid-stable attached (3). During synthesis, resinbound peptides comprising 14 amino acid residues are produced, with each resin bead containing one unique peptide (4,5). The beads are split into 384 pools, with each pool containing 20,000 beads. From each pool, about 28% of the peptide material is cleaved from every bead. Subsequently, in the first screening round, the 384 pools, each containing 20,000 solubilized peptides, are tested in a proliferation assay with the T-cell clone. Fig. 1. Flow diagram of the complete procedure for the identification of T-cell epitopes using synthetic peptide libraries (1).

  7. Facilitating protein solubility by use of peptide extensions

    Science.gov (United States)

    Freimuth, Paul I; Zhang, Yian-Biao; Howitt, Jason

    2013-09-17

    Expression vectors for expression of a protein or polypeptide of interest as a fusion product composed of the protein or polypeptide of interest fused at one terminus to a solubility enhancing peptide extension are provided. Sequences encoding the peptide extensions are provided. The invention further comprises antibodies which bind specifically to one or more of the solubility enhancing peptide extensions.

  8. Cleaving Double-Stranded DNA with Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1997-01-01

    Peptide nucleic acids and analogues of peptide nucleic acids are used to form duplex, triplex, and other structures with nucleic acids and to modify nucleic acids. The peptide nucleic acids and analogues thereof also are used to modulate protein activity through, for example, transcription arrest...

  9. Practical application of natriuretic peptides in paediatric cardiology

    DEFF Research Database (Denmark)

    Smith, Julie; Goetze, Jens Peter; B. Andersen, Claus;

    2010-01-01

    diagnostic tools. Natriuretic peptide measurements could be that extra tool. We discuss and suggest N-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide reference intervals for children without cardiovascular disease and cut-off points for the four specific paediatric heart conditions. We...

  10. Immunodiagnosis of parasitic diseases with synthetic peptides.

    Science.gov (United States)

    Noya, O; Patarroyo, M E; Guzmán, F; Alarcón de Noya, B

    2003-08-01

    Parasitic diseases remain as a major public health problem worldwide, not only based on their historically high morbidity and mortality rates, but also because risk factors associated with their transmission are increasing. Laboratory diagnosis and particularly immunodiagnosis is a basic tool for the demonstration, clinical management and control of these infections. Classically, the serological tests for the detection of antibodies or antigens are based on the use of crude and purified antigens. Synthetic peptides have opened a new field and perspectives, as the source of pure epitopes and molecules for diagnosis of malaria, Chagas' disease, leishmaniasis, schistosomiasis, hidatidosis, cysticercosis and fasciolosis based on the detection of antibodies and circulating antigens. Herein, are critically reviewed the relevant advances and applications of the synthetic peptides on immunodiagnosis of parasitic diseases. A variety of sequences, constructs (monomers, polymers, MAPs), immunological methods and samples have been used, demonstrating their diagnostic potential. However, in most parasitic infections it is necessary to use more than a single peptide in order to avoid the genetic restriction against certain epitopes, as well as to test them in well characteized groups of patients, in order to confirm their sensitivity and specificity. The concept of multidiagnosis with synthetic peptides, using a novel multi-dot blot assay is introduced. Finally, the chemical imitation of antigens, offers a tremendous posibilities in the diagnosis of parasitic infections in developing countries since this strategy is cheaper, simpler, reproducible, useful for large scale testing and in most cases, specific and sensitive. PMID:14529537

  11. Peptide conjugation: before or after nanoparticle formation?

    Science.gov (United States)

    Valetti, Sabrina; Mura, Simona; Noiray, Magali; Arpicco, Silvia; Dosio, Franco; Vergnaud, Juliette; Desmaële, Didier; Stella, Barbara; Couvreur, Patrick

    2014-11-19

    We report herein a detailed study concerning the impact of different bioconjugation and nanoformulation strategies on the in vitro targeting ability of peptide-decorated squalenoyl gemcitabine (SQdFdC) nanoparticles (NPs). NPs have been functionalized with the CKAAKN peptide, previously identified as an efficient homing device within the pancreatic pathological microenvironment. Two approaches have been followed: (i) either the CKAAKN peptide was directly conjugated at the surface of preformed SQdFdC nanoparticles (conjugation after NP formation) or (ii) it was first reacted with a maleimide squalenoyl derivative before the resulting bioconjugate was co-nanoprecipitated with SQdFdC to form the peptide-decorated NPs (conjugation before NP formation). NPs were characterized with respect to mean diameter, zeta potential, and stability over time. Then, their specific interaction with the sFRP-4 protein was evaluated by surface plasmon resonance. Although both synthetic strategies allowed us to formulate NPs able to interact with the corresponding receptor, enhanced target binding and better specific avidity were observed with CKAAKN-NPs functionalized before NP formation. These NPs displayed the highest cell uptake and cytotoxicity in an in vitro model of human MIA Paca-2 pancreatic cancer cells.

  12. Stereocontrolled Synthesis of Methyl Silanediol Peptide Mimics

    DEFF Research Database (Denmark)

    Nielsen, Lone; Lindsay, Karl; Faber, Jesper;

    2007-01-01

    methanolic HCl and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its...

  13. Classification of antimicrobial peptides with imbalanced datasets

    Science.gov (United States)

    Camacho, Francy L.; Torres, Rodrigo; Ramos Pollán, Raúl

    2015-12-01

    In the last years, pattern recognition has been applied to several fields for solving multiple problems in science and technology as for example in protein prediction. This methodology can be useful for prediction of activity of biological molecules, e.g. for determination of antimicrobial activity of synthetic and natural peptides. In this work, we evaluate the performance of different physico-chemical properties of peptides (descriptors groups) in the presence of imbalanced data sets, when facing the task of detecting whether a peptide has antimicrobial activity. We evaluate undersampling and class weighting techniques to deal with the class imbalance with different classification methods and descriptor groups. Our classification model showed an estimated precision of 96% showing that descriptors used to codify the amino acid sequences contain enough information to correlate the peptides sequences with their antimicrobial activity by means of learning machines. Moreover, we show how certain descriptor groups (pseudoaminoacid composition type I) work better with imbalanced datasets while others (dipeptide composition) work better with balanced ones.

  14. A caged substrate peptide for matrix metalloproteinases.

    Science.gov (United States)

    Decaneto, Elena; Abbruzzetti, Stefania; Heise, Inge; Lubitz, Wolfgang; Viappiani, Cristiano; Knipp, Markus

    2015-02-01

    Based on the widely applied fluorogenic peptide FS-6 (Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2; Mca = methoxycoumarin-4-acetyl; Dpa = N-3-(2,4-dinitrophenyl)l-α,β-diaminopropionyl) a caged substrate peptide Ac-Lys-Pro-Leu-Gly-Lys*-Lys-Ala-Arg-NH2 (*, position of the cage group) for matrix metalloproteinases was synthesized and characterized. The synthesis implies the modification of a carbamidated lysine side-chain amine with a photocleavable 2-nitrobenzyl group. Mass spectrometry upon UV irradiation demonstrated the complete photolytic cleavage of the protecting group. Time-resolved laser-flash photolysis at 355 nm in combination with transient absorption spectroscopy determined the biphasic decomposition with τa = 171 ± 3 ms (79%) and τb = 2.9 ± 0.2 ms (21%) at pH 6.0 of the photo induced release of the 2-nitrobenzyl group. The recombinantly expressed catalytic domain of human membrane type I matrix metalloproteinase (MT1-MMP or MMP-14) was used to determine the hydrolysis efficiency of the caged peptide before and after photolysis. It turned out that the cage group sufficiently shields the peptide from peptidase activity, which can be thus controlled by UV light.

  15. Metal Ion Controlled Polymorphism of a Peptide

    DEFF Research Database (Denmark)

    Hemmingsen, Lars Bo Stegeager; Jancso, Attila; Szunyogh, Daniel;

    2011-01-01

    , …) in the peptide, and the ligand and structural preferences of the metal ion (in our studies Zn2+, Cd2+, Hg2+, Cu+/2+). Simultaneously, new species such as metal ion bridged ternary complexes or even oligomers may be formed. In recent previous studies we have observed similar polymorphism of zinc finger model...

  16. Computer-Aided Design of Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Hancock, Robert E.W.; Jenssen, Håvard

    2010-01-01

    An increasing number of reported cases of drug resistant Staphylococcus aureus and Pseudomonas aeruginosa, demonstrate the urgent need for new therapeutics that are effective against such and other multi-drug resistant bacteria. Antimicrobial peptides have for two decades now been looked upon as...

  17. Peptide Amphiphiles in Corneal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Martina Miotto

    2015-08-01

    Full Text Available The increasing interest in effort towards creating alternative therapies have led to exciting breakthroughs in the attempt to bio-fabricate and engineer live tissues. This has been particularly evident in the development of new approaches applied to reconstruct corneal tissue. The need for tissue-engineered corneas is largely a response to the shortage of donor tissue and the lack of suitable alternative biological scaffolds preventing the treatment of millions of blind people worldwide. This review is focused on recent developments in corneal tissue engineering, specifically on the use of self-assembling peptide amphiphiles for this purpose. Recently, peptide amphiphiles have generated great interest as therapeutic molecules, both in vitro and in vivo. Here we introduce this rapidly developing field, and examine innovative applications of peptide amphiphiles to create natural bio-prosthetic corneal tissue in vitro. The advantages of peptide amphiphiles over other biomaterials, namely their wide range of functions and applications, versatility, and transferability are also discussed to better understand how these fascinating molecules can help solve current challenges in corneal regeneration.

  18. Chemical labeling of electrochemically cleaved peptides

    NARCIS (Netherlands)

    Roeser, Julien; Alting, Niels F. A.; Permentier, Hjalmar P.; Bruins, Andries P.; Bischoff, Rainer P. H.

    2013-01-01

    RATIONALE Cleavage of peptide bonds C-terminal to tyrosine and tryptophan after electrochemical oxidation may become a complementary approach to chemical and enzymatic cleavage. A chemical labeling approach specifically targeting reactive cleavage products is presented here and constitutes a promisi

  19. Apelin is a novel islet peptide

    DEFF Research Database (Denmark)

    Ringström, Camilla; Nitert, Marloes Dekker; Bennet, Hedvig;

    2010-01-01

    Apelin, a recently discovered peptide with wide tissue distribution, regulates feeding behavior, improves glucose utilization, and inhibits insulin secretion. We examined whether apelin is expressed in human islets, as well as in normal and type 2 diabetic (T2D) animal islets. Further, we studied...

  20. Release of opioid peptides in anaesthetized cats?

    OpenAIRE

    Dashwood, M. R.; Feldberg, W.

    1980-01-01

    1 The effect on arterial blood pressure of intravenous injections of naloxone (200 μg) was examined in cats anaesthetized with chloralose. Usually these injections have no effect on blood pressure unless morphine or opioid peptides have been injected, when they produce a pressor response with tachycardia.

  1. An introduction to peptide nucleic acid

    DEFF Research Database (Denmark)

    Nielsen, P E; Egholm, M

    1999-01-01

    Peptide Nucleic Acid (PNA) is a powerful new biomolecular tool with a wide range of important applications. PNA mimics the behaviour of DNA and binds complementary nucleic acid strands. The unique chemical, physical and biological properties of PNA have been exploited to produce powerful...

  2. Microbial production of thioether-stabilized peptides

    NARCIS (Netherlands)

    Kuipers, Anneke

    2010-01-01

    This thesis describes the successful biological production and secretion of thioether-stabilized therapeutic peptides. The lantibiotic modification- and transport enzymes NisBTC and LtnM2T involved in the synthesis of the lantibiotics nisin and lacticin 3147, respectively, were exploited for the int

  3. Behavioural actions of vasoactive intestinal peptide (VIP)

    NARCIS (Netherlands)

    Kloet, E.R.; Cottrell, G.A.; Veldhuis, H.D.; Rostene, W.H.

    1984-01-01

    The effect of vasoactive intestinal peptide (VIP) was studied on fear-motivated behaviours, exploration of a novel environment and on novelty and ACTH-induced grooming. VIP was administered via a plastic cannula into the lateral ventricle. Retention of a step-through passive avoidance task was inhib

  4. Ultrafast Hemithioindigo-based peptide-switches

    NARCIS (Netherlands)

    Cordes, Thorben; Elsner, Cord; Herzog, Teja T.; Hoppmann, Christian; Schadendorf, Torsten; Summerer, Wolfram; Rück-Braun, Karola; Zinth, Wolfgang

    2009-01-01

    Four newly synthesized Hemithioindigo-based peptide-switches with changing meta/para-substitution-pattern within the stilbene-part of the molecule are characterized with time-resolved absorption spectroscopy. The different substances undergo a light-induced Z/E-isomerization: the reaction proceeds o

  5. Isolated Gramicidin Peptides Probed by IR Spectroscopy

    NARCIS (Netherlands)

    Rijs, A. M.; Kabelac, M.; Abo-Riziq, A.; Hobza, P.; de Vries, M. S.

    2011-01-01

    We report double-resonant IR/UV ion-dip spectroscopy of neutral gramicidin peptides in the gas phase. The IR spectra of gramicidin A and C, recorded in both the 1000 cm(-1) to 1800 cm(-1) and the 2700 to 3750 cm(-1) region, allow structural analysis. By studying this broad IR range, various local in

  6. Peptide Hormones in the Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2015-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

  7. Structural pattern matching of nonribosomal peptides

    Directory of Open Access Journals (Sweden)

    Leclère Valérie

    2009-03-01

    Full Text Available Abstract Background Nonribosomal peptides (NRPs, bioactive secondary metabolites produced by many microorganisms, show a broad range of important biological activities (e.g. antibiotics, immunosuppressants, antitumor agents. NRPs are mainly composed of amino acids but their primary structure is not always linear and can contain cycles or branchings. Furthermore, there are several hundred different monomers that can be incorporated into NRPs. The NORINE database, the first resource entirely dedicated to NRPs, currently stores more than 700 NRPs annotated with their monomeric peptide structure encoded by undirected labeled graphs. This opens a way to a systematic analysis of structural patterns occurring in NRPs. Such studies can investigate the functional role of some monomeric chains, or analyse NRPs that have been computationally predicted from the synthetase protein sequence. A basic operation in such analyses is the search for a given structural pattern in the database. Results We developed an efficient method that allows for a quick search for a structural pattern in the NORINE database. The method identifies all peptides containing a pattern substructure of a given size. This amounts to solving a variant of the maximum common subgraph problem on pattern and peptide graphs, which is done by computing cliques in an appropriate compatibility graph. Conclusion The method has been incorporated into the NORINE database, available at http://bioinfo.lifl.fr/norine. Less than one second is needed to search for a pattern in the entire database.

  8. Method of producing a peptide mixture

    DEFF Research Database (Denmark)

    2000-01-01

    The present invention relates to a method for industrial production of a peptide preparation having specific specifications by hydrolysis of a protein material, preferably based on whey. The method comprises several steps, which makes it easy to control the method so as to obtain a product which, e...

  9. Exhaustively sampling peptide adsorption with metadynamics.

    Science.gov (United States)

    Deighan, Michael; Pfaendtner, Jim

    2013-06-25

    Simulating the adsorption of a peptide or protein and obtaining quantitative estimates of thermodynamic observables remains challenging for many reasons. One reason is the dearth of molecular scale experimental data available for validating such computational models. We also lack simulation methodologies that effectively address the dual challenges of simulating protein adsorption: overcoming strong surface binding and sampling conformational changes. Unbiased classical simulations do not address either of these challenges. Previous attempts that apply enhanced sampling generally focus on only one of the two issues, leaving the other to chance or brute force computing. To improve our ability to accurately resolve adsorbed protein orientation and conformational states, we have applied the Parallel Tempering Metadynamics in the Well-Tempered Ensemble (PTMetaD-WTE) method to several explicitly solvated protein/surface systems. We simulated the adsorption behavior of two peptides, LKα14 and LKβ15, onto two self-assembled monolayer (SAM) surfaces with carboxyl and methyl terminal functionalities. PTMetaD-WTE proved effective at achieving rapid convergence of the simulations, whose results elucidated different aspects of peptide adsorption including: binding free energies, side chain orientations, and preferred conformations. We investigated how specific molecular features of the surface/protein interface change the shape of the multidimensional peptide binding free energy landscape. Additionally, we compared our enhanced sampling technique with umbrella sampling and also evaluated three commonly used molecular dynamics force fields. PMID:23706011

  10. Peptide specific expansion of CD8(+) T cells by recombinant plate bound MHC/peptide complexes

    DEFF Research Database (Denmark)

    Schmidt, Esben G W; Buus, Soren; Thorn, Mette;

    2009-01-01

    in vitro T cell stimulation was investigated. By use of an antigenic peptide derived from the cytomegalovirus (CMVp) we tested the stimulatory efficacy of recombinant plate bound MHC molecules (PB-MHC), being immobilized in culture plates. A single stimulation of non-adherent peripheral blood...... effect of new stimulatory cocktails, e.g. cytokines and co-stimulatory molecules, by use of the present rapid and easy-to-use method of expanding peptide specific T cells.......Development of methods for efficient in vitro stimulation and expansion of peptide specific CD8(+) T cells is compelling not only with respect to adoptive T cell therapy but also regarding analysis of T cell responses and search for new immunogenic peptides. In the present study, a new approach to...

  11. Metabolism and pharmacokinetic of cyclo-peptides and peptides. Use of radioelement and stable isotopes

    International Nuclear Information System (INIS)

    More and more peptides and proteins are used in therapeutic. Three mainly techniques are used for pharmacokinetic and metabolism studies: immunoassay, radioactively labeled molecules and mass spectrometry. In the first part of this work, we have used uniformly labelled peptides (C-peptide and insulin) with stables (13C, 15N, and 13C/15N) or radioactive (14C) isotopes to investigated these kind of studies. These works are based on isotope dilution mass spectrometry assay. In a second time we have investigated the metabolism of a particular cyclo-peptides families composed of two amino acids: the diketo-piperazine. These compounds are found in mammals and in microorganisms. There are not recognized by proteolytic enzymes. We have estimated if the main enzymes implicated in the metabolism of xenobiotics, the P450 cytochrome mono-oxygenases, were able to recognized them

  12. Novel ZnO-binding peptides obtained by the screening of a phage display peptide library

    Energy Technology Data Exchange (ETDEWEB)

    Golec, Piotr [Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of Molecular Biology (affiliated with the University of Gdansk) (Poland); Karczewska-Golec, Joanna [University of Gdansk and Medical University of Gdansk, Laboratory of Molecular Bacteriology, Intercollegiate Faculty of Biotechnology (Poland); Los, Marcin; Wegrzyn, Grzegorz, E-mail: wegrzyn@biotech.univ.gda.pl [University of Gdansk, Department of Molecular Biology (Poland)

    2012-11-15

    Zinc oxide (ZnO) is a semiconductor compound with a potential for wide use in various applications, including biomaterials and biosensors, particularly as nanoparticles (the size range of ZnO nanoparticles is from 2 to 100 nm, with an average of about 35 nm). Here, we report isolation of novel ZnO-binding peptides, by screening of a phage display library. Interestingly, amino acid sequences of the ZnO-binding peptides reported in this paper and those described previously are significantly different. This suggests that there is a high variability in sequences of peptides which can bind particular inorganic molecules, indicating that different approaches may lead to discovery of different peptides of generally the same activity (e.g., binding of ZnO) but having various detailed properties, perhaps crucial under specific conditions of different applications.

  13. Selection of a peptide mimicking neutralization epitope of hepatitis E virus with phage peptide display technology

    Institute of Scientific and Technical Information of China (English)

    Ying Gu; Jun Zhang; Ying-Bing Wang; Shao-Wei Li; Hai-Jie Yang; Wen-Xin Luo; Ning-Shao Xia

    2004-01-01

    AIM: To select the peptide mimicking the neutralization epitope of hepatitis E virus which bound to non-type-specific and conformational monoclonal antibodies (mAbs) 8C11 and 8H3 fromed 7-peptide phage display library, and expressed the peptide recombinant with HBcAg in E.coli, and to observe whether the recombinant HBcAg could still form virus like particle (VLP) and to test the activation of the recombinant polyprotein and chemo-synthesized peptide that was selected by mAb 8H3.METHODS: 8C11 and 8H3 were used to screen for binding peptides through a 7-peptide phage display library. After 4rounds of panning, monoclonal phages were selected and sequenced. The obtained dominant peptide coding sequences was then synthesized and inserted into amino acid 78 to 83 of hepatitis B core antigen (HBcAg), and then expressed in E. coli. Activity of the recombinant proteins was detected by Western blotting, VLPs of the recombinant polyproteins were tested by transmission electron microscopy and binding activity of the chemo-synthesized peptide was confirmed by BIAcore biosensor.RESULTS: Twenty-one positive monoclonal phages (10for 8CL1, and 11 for 8H3) were selected and the inserted fragments were sequenced. The DNA sequence coding for the obtained dominant peptides 8C11 (N′-His-Pro-Thr-LeuLeu-Arg-Ile-C′, named 8C11A) and 8H3 (N′-Ser-Ile-LeuPro- Tyr-Pro-Tyr-C′, named 8H3A) were then synthesized and cloned to the HBcAg vector, then expressed in E. coli.The recombinant proteins aggregated into homodimer or polymer on SDS-PAGE, and could bind to mAb 8C11 and 8H3 in Western blotting. At the same time, the recombinant polyprotein could form virus like particles (VLPs), which could be visualized on electron micrograph. The dominant peptide 8H3A selected by mAb 8H3 was further chemosynthesized, and its binding to mAb 8H3 could be detected by BIAcore biosensor.CONCLUSION: These results implicate that conformational neutralizing epitope can be partially modeled by a short

  14. Characterization of the Cu(Π) and Zn(Π) binding to the Amyloid-β short peptides by both the Extended X-ray Absorption Fine Structure and the Synchrotron Radiation Circular Dichroism spectroscopy

    Science.gov (United States)

    Zhang, Zhiyin; Sun, Shuaishuai; Xu, Jianhua; Zhang, Jing; Huang, Yan; Zhang, Bingbing; Tao, Ye

    2013-04-01

    Alzheimer's disease (AD) is a progressive and devastating neurodegenerative pathology, clinically characterized by dementia, cognitive impairment, personality disorders and memory loss. It is generally accepted that, misfolding of Aβ peptides is the key element in pathogenesis and the secondary structure of Aβ can be changed to major β-strand with reasons unknown yet. Many studies have shown that the misfolding may be linked with some biometals, mainly copper and zinc ions. To characterize interactions of Aβ and metal ions, we utilized both the extended X-ray fine structure spectroscopy (EXAFS) and the synchrotron radiation circular dichroism spectroscopy (SRCD). Aβ (13-22), Aβ (13-21), Aβ (E22G) and Aβ(HH-AA) were selected to study the mechanism of copper and zinc binding to Aβ. We found that Cu interaction with H13 and H14 residues led to the disappearance of the PPΠ, while the Cu binding E22 residue caused a remarkable conformation change to β-sheet enrichment. The Zn ion, in contrast, made little effect on the conformation and it coordinated to only one histidine (H residue) or not.

  15. Antimicrobial peptides: a review of how peptide structure impacts antimicrobial activity

    Science.gov (United States)

    Soares, Jason W.; Mello, Charlene M.

    2004-03-01

    Antimicrobial peptides (AMPs) have been discovered in insects, mammals, reptiles, and plants to protect against microbial infection. Many of these peptides have been isolated and studied exhaustively to decipher the molecular mechanisms that impart protection against infectious bacteria, fungi, and viruses. Unfortunately, the molecular mechanisms are still being debated within the scientific community but valuable clues have been obtained through structure/function relationship studies1. Biophysical studies have revealed that cecropins, isolated from insects and pigs, exhibit random structure in solution but undergo a conformational change to an amphipathic α-helix upon interaction with a membrane surface2. The lack of secondary structure in solution results in an extremely durable peptide able to survive exposure to high temperatures, organic solvents and incorporation into fibers and films without compromising antibacterial activity. Studies to better understand the antimicrobial action of cecropins and other AMPs have provided insight into the importance of peptide sequence and structure in antimicrobial activities. Therefore, enhancing our knowledge of how peptide structure imparts function may result in customized peptide sequences tailored for specific applications such as targeted cell delivery systems, novel antibiotics and food preservation additives. This review will summarize the current state of knowledge with respect to cell binding and antimicrobial activity of AMPs focusing primarily upon cecropins.

  16. Preparation of peptide thioesters through fmoc-based solid-phase peptide synthesis by using amino thioesters

    DEFF Research Database (Denmark)

    Stuhr-Hansen, N.; Wilbek, T.S.; Strømgaard, K.

    2013-01-01

    An effective procedure for the synthesis of peptide alkyl thioesters by 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis was developed. The free C terminus of a fully protected peptide was coupled in solution with the free amino group of an amino thioester. This furnished the fully...

  17. Synthesis of peptide thioacids at neutral pH using bis(2-sulfanylethyl)amido peptide precursors.

    Science.gov (United States)

    Pira, Silvain L; Boll, Emmanuelle; Melnyk, Oleg

    2013-10-18

    Reaction of bis(2-sulfanylethyl)amido (SEA) peptides with triisopropylsilylthiol in water at neutral pH yields peptide thiocarboxylates. An alkylthioester derived from β-alanine was used to trap the released bis(2-sulfanylethyl)amine and displace the equilibrium toward the peptide thiocarboxylate. PMID:24073852

  18. A cardioactive peptide from the southern armyworm, Spodoptera eridania.

    Science.gov (United States)

    Furuya, K; Hackett, M; Cirelli, M A; Schegg, K M; Wang, H; Shabanowitz, J; Hunt, D F; Schooley, D A

    1999-01-01

    A cardioactive peptide was isolated from extracts of whole heads of the southern armyworm, Spodoptera eridania. This peptide has the sequence ENFAVGCTPGYQRTADGRCKPTF (Mr = 2516.8), determined from both Edman sequencing and tandem mass spectrometry in combination with off-line micropreparative capillary liquid chromatography. This peptide, termed Spoer-CAP23, has excitatory effects on a semi-isolated heart from larval Manduca sexta, causing an inotropic effect at low concentrations of peptide and chronotropic and inotropic effects at high doses. The threshold concentration for stimulatory effects of the synthetic peptide on the semi-isolated heart was about 1 nM, suggesting a physiological role as a neuropeptide. PMID:10098624

  19. Peptide-Loaded Solid Lipid Nanoparticles Prepared through Coacervation Technique

    Directory of Open Access Journals (Sweden)

    Marina Gallarate

    2011-01-01

    Full Text Available Stearic acid solid lipid nanoparticles were prepared according to a new technique, called coacervation. The main goal of this experimental work was the entrapment of peptide drugs into SLN, which is a difficult task, since their chemical characteristics (molecular weight, hydrophilicity, and stability hamper peptide-containing formulations. Insulin and leuprolide, chosen as model peptide drugs, were encapsulated within nanoparticles after hydrophobic ion pairing with anionic surfactants. Peptide integrity was maintained after encapsulation, and nanoparticles can act in vitro as a sustained release system for peptide.

  20. Morphogenic Peptides in Regeneration of Load Bearing Tissues.

    Science.gov (United States)

    Moeinzadeh, Seyedsina; Jabbari, Esmaiel

    2015-01-01

    Morphogenic proteins due to their short half-life require high doses of growth factors in regeneration of load bearing tissues which leads to undesirable side effects. These side effects include bone overgrowth, tumor formation and immune reaction. An alternative approach to reduce undesirable side effects of proteins in regenerative medicine is to use morphogenic peptides derived from the active domains of morphogenic proteins or soluble and insoluble components of the extracellular matrix of mineralized load bearing tissues to induce differentiation of progenitor cells, mineralization, maturation and bone formation. In that regard, many peptides with osteogenic activity have been discovered. These include peptides derived from bone morphogenic proteins (BMPs), those based on interaction with integrin and heparin-binding receptors, collagen derived peptides, peptides derived from other soluble ECM proteins such as bone sialoprotein and enamel matrix proteins, and those peptides derived from vasculoinductive and neuro-inductive proteins. Although these peptides show significant osteogenic activity in vitro and increase mineralization and bone formation in animal models, they are not widely used in clinical orthopedic applications as an alternative to morphogenic proteins. This is partly due to the limited availability of data on structure and function of morphogenic peptides in physiological medium, particularly in tissue engineered scaffolds. Due to their amphiphilic nature, peptides spontaneously self-assemble and aggregate into micellar structures in physiological medium. Aggregation alters the sequence of amino acids in morphogenic peptides that interact with cell surface receptors thus affecting osteogenic activity of the peptide. Aggregation and micelle formation can dramatically reduce the active concentration of morphogenic peptides with many-fold increase in peptide concentration in physiological medium. Other factors that affect bioactivity are the non

  1. Peptide-based Biopolymers in Biomedicine and Biotechnology

    Science.gov (United States)

    Chow, Dominic; Nunalee, Michelle L.; Lim, Dong Woo; Simnick, Andrew J.; Chilkoti, Ashutosh

    2008-01-01

    Peptides are emerging as a new class of biomaterials due to their unique chemical, physical, and biological properties. The development of peptide-based biomaterials is driven by the convergence of protein engineering and macromolecular self-assembly. This review covers the basic principles, applications, and prospects of peptide-based biomaterials. We focus on both chemically synthesized and genetically encoded peptides, including poly-amino acids, elastin-like polypeptides, silk-like polymers and other biopolymers based on repetitive peptide motifs. Applications of these engineered biomolecules in protein purification, controlled drug delivery, tissue engineering, and biosurface engineering are discussed. PMID:19122836

  2. Molecular imaging of cancer with radiolabeled peptides and PET.

    Science.gov (United States)

    Vāvere, Amy L; Rossin, Raffaella

    2012-06-01

    Radiolabeled peptides hold promise for diagnosis and therapy of cancer as well as for early monitoring of therapy outcomes, patient stratification, etc. This manuscript focuses on the development of peptides labeled with 18F, 64Cu, 68Ga and other positron-emitting radionuclides for PET imaging. The major techniques for radionuclide incorporation are briefly discussed. Then, examples of positron-emitting peptides targeting somatostatin receptors, integrins, gastrin-releasing peptide receptors, vasointestinal peptide receptors, melanocortin 1 receptors and others are reviewed. PMID:22292762

  3. Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Faber, O K;

    1989-01-01

    Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated...... with a fasting plasma C-peptide value less than 0.20 nmol/l, a glucagon stimulated plasma C-peptide value less than 0.32 nmol/l, and a urinary C-peptide value less than 3.1 nmol/l, or less than 0.54 nmol/mmol creatinine/24 h, or less than 5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C...

  4. Towards Identify Selective Antibacterial Peptides Based on Abstracts Meaning

    Science.gov (United States)

    Barbosa-Santillán, Liliana I.; Sánchez-Escobar, Juan J.; Calixto-Romo, M. Angeles; Barbosa-Santillán, Luis F.

    2016-01-01

    We present an Identify Selective Antibacterial Peptides (ISAP) approach based on abstracts meaning. Laboratories and researchers have significantly increased the report of their discoveries related to antibacterial peptides in primary publications. It is important to find antibacterial peptides that have been reported in primary publications because they can produce antibiotics of different generations that attack and destroy the bacteria. Unfortunately, researchers used heterogeneous forms of natural language to describe their discoveries (sometimes without the sequence of the peptides). Thus, we propose that learning the words meaning instead of the antibacterial peptides sequence is possible to identify and predict antibacterial peptides reported in the PubMed engine. The ISAP approach consists of two stages: training and discovering. ISAP founds that the 35% of the abstracts sample had antibacterial peptides and we tested in the updated Antimicrobial Peptide Database 2 (APD2). ISAP predicted that 45% of the abstracts had antibacterial peptides. That is, ISAP found that 810 antibacterial peptides were not classified like that, so they are not reported in APD2. As a result, this new search tool would complement the APD2 with a set of peptides that are candidates to be antibacterial. Finally, 20% of the abstracts were not semantic related to APD2. PMID:27366202

  5. Peptides Interfering 3A Protein Dimerization Decrease FMDV Multiplication.

    Directory of Open Access Journals (Sweden)

    Mónica González-Magaldi

    Full Text Available Nonstructural protein 3A is involved in relevant functions in foot-and-mouth disease virus (FMDV replication. FMDV 3A can form homodimers and preservation of the two hydrophobic α-helices (α1 and α2 that stabilize the dimer interface is essential for virus replication. In this work, small peptides mimicking residues involved in the dimer interface were used to interfere with dimerization and thus gain insight on its biological function. The dimer interface peptides α1, α2 and that spanning the two hydrophobic α-helices, α12, impaired in vitro dimer formation of a peptide containing the two α-helices, this effect being higher with peptide α12. To assess the effect of dimer inhibition in cultured cells, the interfering peptides were N-terminally fused to a heptaarginine (R7 sequence to favor their intracellular translocation. Thus, when fused to R7, interference peptides (100 μM were able to inhibit dimerization of transiently expressed 3A, the higher inhibitions being found with peptides α1 and α12. The 3A dimerization impairment exerted by the peptides correlated with significant, specific reductions in the viral yield recovered from peptide-treated FMDV infected cells. In this case, α2 was the only peptide producing significant reductions at concentrations lower than 100 μM. Thus, dimer interface peptides constitute a tool to understand the structure-function relationship of this viral protein and point to 3A dimerization as a potential antiviral target.

  6. Development of peptide-based patterns by laser transfer

    Science.gov (United States)

    Dinca, V.; Kasotakis, E.; Catherine, J.; Mourka, A.; Mitraki, A.; Popescu, A.; Dinescu, M.; Farsari, M.; Fotakis, C.

    2007-12-01

    Peptide-based arrays and patterns have provided a powerful tool in the study of protein recognition and function. A variety of applications have been identified, including the interactions between peptides-enzymes, peptides-proteins, peptides-DNA, peptides-small molecules and peptides-cells. One of the main and most critical unresolved issues is the generation of high-density arrays which maintain the biological function of the peptides. In this study, we employ nanosecond laser-induced forward transfer for the generation of high-density peptide arrays and patterns on modified glass surfaces. We show that peptide-based microarrays can be fabricated on solid surfaces and specifically recognized by appropriate fluorescent tags, with the transfer not affecting the ability of the peptides to form fibrils. These initial results are poised to the construction of larger peptide patterns as scaffolds for the incorporation and display of ligands critical for cell attachment and growth, or for the templating of inorganic materials.

  7. Towards Identify Selective Antibacterial Peptides Based on Abstracts Meaning.

    Science.gov (United States)

    Barbosa-Santillán, Liliana I; Sánchez-Escobar, Juan J; Calixto-Romo, M Angeles; Barbosa-Santillán, Luis F

    2016-01-01

    We present an Identify Selective Antibacterial Peptides (ISAP) approach based on abstracts meaning. Laboratories and researchers have significantly increased the report of their discoveries related to antibacterial peptides in primary publications. It is important to find antibacterial peptides that have been reported in primary publications because they can produce antibiotics of different generations that attack and destroy the bacteria. Unfortunately, researchers used heterogeneous forms of natural language to describe their discoveries (sometimes without the sequence of the peptides). Thus, we propose that learning the words meaning instead of the antibacterial peptides sequence is possible to identify and predict antibacterial peptides reported in the PubMed engine. The ISAP approach consists of two stages: training and discovering. ISAP founds that the 35% of the abstracts sample had antibacterial peptides and we tested in the updated Antimicrobial Peptide Database 2 (APD2). ISAP predicted that 45% of the abstracts had antibacterial peptides. That is, ISAP found that 810 antibacterial peptides were not classified like that, so they are not reported in APD2. As a result, this new search tool would complement the APD2 with a set of peptides that are candidates to be antibacterial. Finally, 20% of the abstracts were not semantic related to APD2. PMID:27366202

  8. De-novo design of antimicrobial peptides for plant protection.

    Directory of Open Access Journals (Sweden)

    Benjamin Zeitler

    Full Text Available This work describes the de-novo design of peptides that inhibit a broad range of plant pathogens. Four structurally different groups of peptides were developed that differ in size and position of their charged and hydrophobic clusters and were assayed for their ability to inhibit bacterial growth and fungal spore germination. Several peptides are highly active at concentrations between 0,1 and 1 µg/ml against plant pathogenic bacteria, such as Pseudomonas syringae, Pectobacterium carotovorum, and Xanthomonas vesicatoria. Importantly, no hemolytic activity could be detected for these peptides at concentrations up to 200 µg/ml. Moreover, the peptides are also active after spraying on the plant surface demonstrating a possible way of application. In sum, our designed peptides represent new antimicrobial agents and with the increasing demand for antimicrobial compounds for production of "healthy" food, these peptides might serve as templates for novel antibacterial and antifungal agents.

  9. Review seed biopharmaceutical cyclic peptides: From discovery to applications.

    Science.gov (United States)

    Mahatmanto, Tunjung

    2015-11-01

    Mini-proteins (or peptides) with disulfide bond/s and a cyclic backbone offer exciting opportunities for applications in medicine, as these ribosomally synthesized and posttranslationally modified peptides are exceptionally stable and amenable to grafting epitopes with desirable activities. Here I discuss important aspects of the discovery and applications of disulfide-bonded cyclic peptides from seeds, i.e., the trypsin inhibitor cyclotides and the preproalbumin with sunflower trypsin inhibitor-derived peptides, focusing on bioanalytical methods for and insights generated from their discovery as well as their potential use as engineering scaffolds for peptide-based drug design. The recent discovery of their precursors and processing enzymes could potentially enable in planta production of designer disulfide-bonded cyclic peptides, preferably in edible seeds, and address the demand for new biopharmaceutical peptides in a cost-effective manner. PMID:26385189

  10. Short peptides allowing preferential detection of Candida albicans hyphae.

    Science.gov (United States)

    Kaba, Hani E J; Pölderl, Antonia; Bilitewski, Ursula

    2015-09-01

    Whereas the detection of pathogens via recognition of surface structures by specific antibodies and various types of antibody mimics is frequently described, the applicability of short linear peptides as sensor molecules or diagnostic tools is less well-known. We selected peptides which were previously reported to bind to recombinant S. cerevisiae cells, expressing members of the C. albicans Agglutinin-Like-Sequence (ALS) cell wall protein family. We slightly modified amino acid sequences to evaluate peptide sequence properties influencing binding to C. albicans cells. Among the selected peptides, decamer peptides with an "AP"-N-terminus were superior to shorter peptides. The new decamer peptide FBP4 stained viable C. albicans cells more efficiently in their mature hyphal form than in their yeast form. Moreover, it allowed distinction of C. albicans from other related Candida spp. and could thus be the basis for the development of a useful tool for the diagnosis of invasive candidiasis.

  11. Adding energy minimization strategy to peptide-design algorithm enables better search for RNA-binding peptides: Redesigned λ N peptide binds boxB RNA.

    Science.gov (United States)

    Xiao, Xingqing; Hung, Michelle E; Leonard, Joshua N; Hall, Carol K

    2016-10-15

    Our previously developed peptide-design algorithm was improved by adding an energy minimization strategy which allows the amino acid sidechains to move in a broad configuration space during sequence evolution. In this work, the new algorithm was used to generate a library of 21-mer peptides which could substitute for λ N peptide in binding to boxB RNA. Six potential peptides were obtained from the algorithm, all of which exhibited good binding capability with boxB RNA. Atomistic molecular dynamics simulations were then conducted to examine the ability of the λ N peptide and three best evolved peptides, viz. Pept01, Pept26, and Pept28, to bind to boxB RNA. Simulation results demonstrated that our evolved peptides are better at binding to boxB RNA than the λ N peptide. Sequence searches using the old (without energy minimization strategy) and new (with energy minimization strategy) algorithms confirm that the new algorithm is more effective at finding good RNA-binding peptides than the old algorithm. © 2016 Wiley Periodicals, Inc.

  12. Inhibition of aggregation of amyloid peptides by beta-sheet breaker peptides and their binding affinity.

    Science.gov (United States)

    Viet, Man Hoang; Ngo, Son Tung; Lam, Nguyen Sy; Li, Mai Suan

    2011-06-01

    The effects of beta-sheet breaker peptides KLVFF and LPFFD on the oligomerization of amyloid peptides were studied by all-atom simulations. It was found that LPFFD interferes the aggregation of Aβ(16-22) peptides to a greater extent than does KLVFF. Using the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method, we found that the former binds more strongly to Aβ(16-22). Therefore, by simulations, we have clarified the relationship between aggregation rates and binding affinity: the stronger the ligand binding, the slower the oligomerization process. The binding affinity of pentapeptides to full-length peptide Aβ(1-40) and its mature fibrils has been considered using the Autodock and MM-PBSA methods. The hydrophobic interaction between ligands and receptors plays a more important role for association than does hydrogen bonding. The influence of beta-sheet breaker peptides on the secondary structures of monomer Aβ(1-40) was studied in detail, and it turns out that, in their presence, the total beta-sheet content can be enhanced. However, the aggregation can be slowed because the beta-content is reduced in fibril-prone regions. Both pentapeptides strongly bind to monomer Aβ(1-40), as well as to mature fibrils, but KLVFF displays a lower binding affinity than LPFFD. Our findings are in accord with earlier experiments that both of these peptides can serve as prominent inhibitors. In addition, we predict that LPFFD inhibits/degrades the fibrillogenesis of full-length amyloid peptides better than KLVFF. This is probably related to a difference in their total hydrophobicities in that the higher the hydrophobicity, the lower the inhibitory capacity. The GROMOS96 43a1 force field with explicit water and the force field proposed by Morris et al. (Morris et al. J. Comput. Chem. 1998, 19, 1639 ) were employed for all-atom molecular dynamics simulations and Autodock experiments, respectively. PMID:21563780

  13. Towards the anti-fibrillogenic activity of phthalocyanines with out-of-plane ligands: correlation with self-association proneness

    Directory of Open Access Journals (Sweden)

    Kovalska V. B.

    2013-11-01

    Full Text Available Aim. The activity of five hafnium phthalocyanines containing out-of-plane ligands as inhibitors of reaction of insulin fibril formation is studied and correlation between their inhibitory properties and tendency to self-association is discussed. Methods. Fluorescence and absorption spectroscopy. Results. For the complexes with weak proneness to self-association PcHfDbm2, PcHfPyr2, and PcHfBtfa2 the values of inhibitory activity were estimated as 60–73 %. For phthalocyanines with the pronounced tendency to self-association PcHfPiromelit and PcHfCl2 the noticeably higher inhibitory activity values (about 95 % were shown. In the presence of native or fibrilar insulin the destruction of self-associates of metal complex occurs in buffer pH 7.9, Besides upon the conditions of insulin fibrillization reaction (0.1 M HCl phthalocyanines exist predominantly as monomers. Conclusions. The phthalocyanines with out-of-plane ligands with higher tendency to self-association have shown higher inhibitory activity in the insulin fibril formation comparing with the poorly aggregated metal complexes. At the same time low-order self-associates are not involved directly in the mechanism of inhibition of insulin fibrillization and the phthalocyanines bind with protein in monomeric form. Tendency of phthalocyanines to self-association in aqueous media seems to be an «indicator» of their proneness to stack with protein aromatic amino-acids and thus of anti-fibrilogenic properties.

  14. Synthesis of biologically important neutral amylo-β peptide by using improved Fmoc solid-phase peptide synthetic strategy.

    Science.gov (United States)

    Selvam, R; Sudha, E; Rajkumar, P R; Subashchandran, K P

    2015-04-01

    The 10 amino acid sequence of the biologically important neutral amylo-β peptide has equally hydrophilic and hydrophobic properties, which reduces the coupling efficiency during its synthesis and reduces the final yield of the peptide, and is therefore classified as a "difficult peptide sequence." The method presented here minimizes the synthetic problems by the introduction of improved Fmoc chemistry and effective hydroxybenzotriazole (HoBt), diisopropylcarbodiimide (DIC)-coupling and activation strategies. In addition, we developed a PS-TPGD resin as a solid support for the synthesis of specific neutral peptides, which is still a challenge to peptide chemistry. The most essential biologically active neutral amylo-β peptide (KVKRIILARS) was successfully synthesized, and some synthetic modification was performed using the Fmoc solid-phase peptide synthesis (SPPS) method for purity and yield improvement. Graphical abstractᅟ.

  15. Exhaustive extraction of peptides by electromembrane extraction

    DEFF Research Database (Denmark)

    Huang, Chuixiu; Gjelstad, Astrid; Pedersen-Bjergaard, Stig

    2015-01-01

    trifluoroacetate, and leu-enkephalin were extracted from 600 μL of 25 mM phosphate buffer (pH 3.5), through a supported liquid membrane (SLM) containing di-(2-ethylhexyl)-phosphate (DEHP) dissolved in an organic solvent, and into 600 μL of an acidified aqueous acceptor solution using a thin flat membrane-based EME......This fundamental work illustrates for the first time the possibility of exhaustive extraction of peptides using electromembrane extraction (EME) under low system-current conditions (... device. Mass transfer of peptides across the SLM was enhanced by complex formation with the negatively charged DEHP. The composition of the SLM and the extraction voltage were important factors influencing recoveries and current with the EME system. 1-nonanol diluted with 2-decanone (1:1 v/v) containing...

  16. Biodegradable Polyphosphazene Based Peptide-Polymer Hybrids

    Directory of Open Access Journals (Sweden)

    Anne Linhardt

    2016-04-01

    Full Text Available A novel series of peptide based hybrid polymers designed to undergo enzymatic degradation is presented, via macrosubstitution of a polyphosphazene backbone with the tetrapeptide Gly-Phe-Leu-Gly. Further co-substitution of the hybrid polymers with hydrophilic polyalkylene oxide Jeffamine M-1000 leads to water soluble and biodegradable hybrid polymers. Detailed degradation studies, via 31P NMR spectroscopy, dynamic light scattering and field flow fractionation show the polymers degrade via a combination of enzymatic, as well as hydrolytic pathways. The peptide sequence was chosen due to its known property to undergo lysosomal degradation; hence, these degradable, water soluble polymers could be of significant interest for the use as polymer therapeutics. In this context, we investigated conjugation of the immune response modifier imiquimod to the polymers via the tetrapeptide and report the self-assembly behavior of the conjugate, as well as its enzymatically triggered drug release behavior.

  17. Secondary structure of fluorescence labelled synthetic peptides

    CERN Document Server

    Martin, A S

    2000-01-01

    A series of eight synthetic oligopeptides has been prepared and their secondary structures investigated using various techniques. The project represents a continuation of an investigation into thermally induced changes in secondary structure. Following the previously reported results, the change in structure was initially thought to represent a change from an alpha-helix at low temperature to 3 sub 1 sub 0 -helix at high temperature. However, the results reported herein suggest the peptides retain an alpha-helical configuration at all temperatures studied, but that this helix can adopt at least two related forms. The difference in the structures relates to the nature of the H-bonds which may or may not involve an additional interaction from water molecules or side-chains. The peptides were encouraged to adopt a helical configuration by the inclusion of alpha- aminoisobutyric acid (Aib) residues. Also, modified forms of glutamic acid were included in the sequences. These had pendant donor (4-methoxy naphthalen...

  18. Therapeutic antimicrobial peptides may compromise natural immunity.

    Science.gov (United States)

    Habets, Michelle G J L; Brockhurst, Michael A

    2012-06-23

    Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. Evolved resistance was costly in terms of impaired growth rate, but costs-of-resistance were completely ameliorated by compensatory adaptation. Crucially, we show that, in some populations, experimentally evolved resistance to pexiganan provided S. aureus with cross-resistance to human-neutrophil-defensin-1, a key component of the innate immune response to infection. This unintended consequence of therapeutic use could drastically undermine our innate immune system's ability to control and clear microbial infections. Our results therefore highlight grave potential risks of AMP therapies, with implications for their development.

  19. Separation of Peptides by Pressurized Capillary Electrochromatography

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel gradient pressurized capillary electrochromatography (pCEC) instrument wasdeveloped to separate peptides. Two gradient elution modes, hydrophobic and hydrophilicinteraction mode in pCEC, were performed on this instrument. Baseline separation of sixpeptides was obtained on two gradient modes with C18 column and strong cationic exchangecolumn respectively. The effects of mixer volume and total flow rate of pumps on resolutionwere also discussed.

  20. Production and Screening of Monoclonal Peptide Antibodies.

    Science.gov (United States)

    Trier, Nicole Hartwig; Mortensen, Anne; Schiolborg, Annette; Friis, Tina

    2015-01-01

    Hybridoma technology is a remarkable and indispensable tool for generating high-quality monoclonal antibodies. Hybridoma-derived monoclonal antibodies not only serve as powerful research and diagnostic reagents, but have also emerged as the most rapidly expanding class of therapeutic biologicals. In this chapter, an overview of hybridoma technology and the laboratory procedures used routinely for hybridoma production and antibody screening are presented, including characterization of peptide antibodies.

  1. Spider-Venom Peptides as Therapeutics

    OpenAIRE

    Glenn F King; Volker Herzig; Rash, Lachlan D; Jensen, Jonas E.; Sing Yan Er; Sebastian Senff; Saez, Natalie J.

    2010-01-01

    Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more ...

  2. Characterizing Intercellular Signaling Peptides in Drug Addiction

    OpenAIRE

    Romanova, Elena V.; Hatcher, Nathan G.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2008-01-01

    Intercellular signaling peptides (SPs) coordinate the activity of cells and influence organism behavior. SPs, a chemically and structurally diverse group of compounds responsible for transferring information between neurons, are broadly involved in neural plasticity, learning and memory, as well as in drug addiction phenomena. Historically, SP discovery and characterization has tracked advances in measurement capabilities. Today, a suite of analytical technologies is available to investigate ...

  3. Screening Peptide Inhibitors Using Phage Peptide Library with Isocitrate Lyase in Mycobacterium tuberculosis as Target

    Institute of Scientific and Technical Information of China (English)

    YIN Yu-he; NIU Xue; SUN Bo; TENG Guo-sheng; ZHAO Yun-hui; WU Cong-mei

    2011-01-01

    When devoured by macrophages,Mycobacterium tuberculosis remains persistent in macrophages and gains energy through the glyoxylate bypass to maintain its long-term existence in host cells.Therefore it is possible to stop persistent infections by interdicting the glyoxylate bypass in which the isocitrate lyase(ICL) is the key rate-limiting enzyme and a persistence factor.ICL is the target of anti-TB(TB:tubercular) drugs,which could screen ICL out and effectively inhibit the activity of ICL in Mycobacterium tuberculosis,and because of this,anti-TB drugs can be used to kill persistent Mycobacterium tuberculosis.In this study,the ICL gene of the Mycobacterium tuberculosis H37Rv was cloned successfully and recombinant protein with bioactivity was obtained through the enzyme characteristic appraisal.The specific activity of the recombined ICL is 24 μmol·mg-1 -min-1.The recombined ICL protein was used as the target,and phages which can specifically combine to ICL were screened in the phage 7 peptide library.According to the results of the ELISA and DNA sequence detection,eventually three 7-peptide chains were synthesized.Then the peptide chains were reacted with ICL,respectively,to detect their inhibitory effects on ICL.The results show that all the three 7-peptide chains possessed varying inhibitory effects on the activity of ICL.This study provided lead compounds for the research and development of new peptide anti-TB drugs.

  4. Biomimetic peptide-based models of [FeFe]-hydrogenases: utilization of phosphine-containing peptides.

    Science.gov (United States)

    Roy, Souvik; Nguyen, Thuy-Ai D; Gan, Lu; Jones, Anne K

    2015-09-01

    Two synthetic strategies for incorporating diiron analogues of [FeFe]-hydrogenases into short peptides via phosphine functional groups are described. First, utilizing the amine side chain of lysine as an anchor, phosphine carboxylic acids can be coupled via amide formation to resin-bound peptides. Second, artificial, phosphine-containing amino acids can be directly incorporated into peptides via solution phase peptide synthesis. The second approach is demonstrated using three amino acids each with a different phosphine substituent (diphenyl, diisopropyl, and diethyl phosphine). In total, five distinct monophosphine-substituted, diiron model complexes were prepared by reaction of the phosphine-peptides with diiron hexacarbonyl precursors, either (μ-pdt)Fe2(CO)6 or (μ-bdt)Fe2(CO)6 (pdt = propane-1,3-dithiolate, bdt = benzene-1,2-dithiolate). Formation of the complexes was confirmed by UV/Vis, FTIR and (31)P NMR spectroscopy. Electrocatalysis by these complexes is reported in the presence of acetic acid in mixed aqueous-organic solutions. Addition of water results in enhancement of the catalytic rates.

  5. Mass spectrometric survey of peptides in cephalopods with an emphasis on the FMRFamide-related peptides.

    Science.gov (United States)

    Sweedler, J V; Li, L; Floyd, P; Gilly, W

    2000-12-01

    A matrix-assisted laser desorption/ionization (MALDI) mass spectrometric (MS) survey of the major peptides in the stellar, fin and pallial nerves and the posterior chromatophore lobe of the cephalopods Sepia officinalis, Loligo opalescens and Dosidicus gigas has been performed. Although a large number of putative peptides are distinct among the three species, several molecular masses are conserved. In addition to peptides, characterization of the lipid content of the nerves is reported, and these lipid peaks account for many of the lower molecular masses observed. One conserved set of peaks corresponds to the FMRFamide-related peptides (FRPs). The Loligo opalescens FMRFa gene has been sequenced. It encodes a 331 amino acid residue prohormone that is processed into 14 FRPs, which are both predicted by the nucleotide sequence and confirmed by MALDI MS. The FRPs predicted by this gene (FMRFa, FLRFa/FIRFa and ALSGDAFLRFa) are observed in all three species, indicating that members of this peptide family are highly conserved across cephalopods. PMID:11060217

  6. SH3 domain-peptide binding energy calculations based on structural ensemble and multiple peptide templates.

    Directory of Open Access Journals (Sweden)

    Seungpyo Hong

    Full Text Available SH3 domains mediate signal transduction by recognizing short peptides. Understanding of the driving forces in peptide recognitions will help us to predict the binding specificity of the domain-peptide recognition and to understand the molecular interaction networks of cells. However, accurate calculation of the binding energy is a tough challenge. In this study, we propose three ideas for improving our ability to predict the binding energy between SH3 domains and peptides: (1 utilizing the structural ensembles sampled from a molecular dynamics simulation trajectory, (2 utilizing multiple peptide templates, and (3 optimizing the sequence-structure mapping. We tested these three ideas on ten previously studied SH3 domains for which SPOT analysis data were available. The results indicate that calculating binding energy using the structural ensemble was most effective, clearly increasing the prediction accuracy, while the second and third ideas tended to give better binding energy predictions. We applied our method to the five SH3 targets in DREAM4 Challenge and selected the best performing method.

  7. Ribosome evolution: Emergence of peptide synthesis machinery

    Indian Academy of Sciences (India)

    Koji Tamura

    2011-12-01

    Proteins, the main players in current biological systems, are produced on ribosomes by sequential amide bond (peptide bond) formations between amino-acid-bearing tRNAs. The ribosome is an exquisite super-complex of RNA-proteins, containing more than 50 proteins and at least 3 kinds of RNAs. The combination of a variety of side chains of amino acids (typically 20 kinds with some exceptions) confers proteins with extraordinary structure and functions. The origin of peptide bond formation and the ribosome is crucial to the understanding of life itself. In this article, a possible evolutionary pathway to peptide bond formation machinery (proto-ribosome) will be discussed, with a special focus on the RNA minihelix (primordial form of modern tRNA) as a starting molecule. Combining the present data with recent experimental data, we can infer that the peptidyl transferase center (PTC) evolved from a primitive system in the RNA world comprising tRNA-like molecules formed by duplication of minihelix-like small RNA.

  8. Multifunctional matrices for oral peptide delivery.

    Science.gov (United States)

    Bernkop-Schnürch, A; Walker, G

    2001-01-01

    The oral administration of peptide drugs represents one of the greatest challenges in pharmaceutical technology. To gain a sufficient bioavailability of these therapeutic agents, various barriers including the mucus-layer barrier, the enzymatic barrier, and the membrane barrier have to be overcome. A promising strategy for achieving this goal is the use of multifunctional matrices. These matrices are based on polymers that display mucoadhesive properties, a permeation-enhancing effect, enzyme-inhibiting properties, and/or a high buffer capacity. Moreover, a sustained or delayed drug release can be provided by delivery systems that contain such polymers. Among them, polyacrylates, cellulose derivatives, and chitosan are promising excipients that can also be customized by chemical modification to improve certain properties. For example, the covalent attachment of thiol moieties on these polymers leads to improved mucoadhesive and permeation-enhancing properties, and the conjugation of enzyme inhibitors enables the matrices to provide protection for peptide drugs against enzymatic degradation. The efficacy of multifunctional matrices in oral peptide delivery has been verified by various in vivo studies that could pave the way for the development of commercially viable formulations. PMID:11763498

  9. Antimicrobial peptides in echinoderm host defense.

    Science.gov (United States)

    Li, Chun; Blencke, Hans-Matti; Haug, Tor; Stensvåg, Klara

    2015-03-01

    Antimicrobial peptides (AMPs) are important effector molecules in innate immunity. Here we briefly summarize characteristic traits of AMPs and their mechanisms of antimicrobial activity. Echinoderms live in a microbe-rich marine environment and are known to express a wide range of AMPs. We address two novel AMP families from coelomocytes of sea urchins: cysteine-rich AMPs (strongylocins) and heterodimeric AMPs (centrocins). These peptide families have conserved preprosequences, are present in both adults and pluteus stage larvae, have potent antimicrobial properties, and therefore appear to be important innate immune effectors. Strongylocins have a unique cysteine pattern compared to other cysteine-rich peptides, which suggests a novel AMP folding pattern. Centrocins and SdStrongylocin 2 contain brominated tryptophan residues in their native form. This review also includes AMPs isolated from other echinoderms, such as holothuroidins, fragments of beta-thymosin, and fragments of lectin (CEL-III). Echinoderm AMPs are crucial molecules for the understanding of echinoderm immunity, and their potent antimicrobial activity makes them potential precursors of novel drug leads. PMID:25445901

  10. Potential Anticarcinogenic Peptides from Bovine Milk

    Directory of Open Access Journals (Sweden)

    Giacomo Pepe

    2013-01-01

    Full Text Available Bovine milk possesses a protein system constituted by two major families of proteins: caseins (insoluble and whey proteins (soluble. Caseins (αS1, αS2, β, and κ are the predominant phosphoproteins in the milk of ruminants, accounting for about 80% of total protein, while the whey proteins, representing approximately 20% of milk protein fraction, include β-lactoglobulin, α-lactalbumin, immunoglobulins, bovine serum albumin, bovine lactoferrin, and lactoperoxidase, together with other minor components. Different bioactivities have been associated with these proteins. In many cases, caseins and whey proteins act as precursors of bioactive peptides that are released, in the body, by enzymatic proteolysis during gastrointestinal digestion or during food processing. The biologically active peptides are of particular interest in food science and nutrition because they have been shown to play physiological roles, including opioid-like features, as well as immunomodulant, antihypertensive, antimicrobial, antiviral, and antioxidant activities. In recent years, research has focused its attention on the ability of these molecules to provide a prevention against the development of cancer. This paper presents an overview of antitumor activity of caseins and whey proteins and derived peptides.

  11. Peptides: Basic determinants of reproductive functions.

    Science.gov (United States)

    Celik, Onder; Aydin, Suleyman; Celik, Nilufer; Yilmaz, Musa

    2015-10-01

    Mammalian reproduction is a costly process in terms of energy consumption. The critical information regarding metabolic status is signaled to the hypothalamus mainly through peripheral peptides from the adipose tissue and gastrointestinal tract. Changes in energy stores produce fluctuations in leptin, insulin, ghrelin and glucose signals that feedback mainly to the hypothalamus to regulate metabolism and fertility. In near future, possible effects of the nutritional status on GnRH regulation can be evaluated by measuring serum or tissue levels of leptin and ghrelin in patiens suffering from infertility. The fact that leptin and ghrelin are antagonistic in their effects on GnRH neurons, their respective agonistic and antagonistic roles make them ideal candidates to use instead of GnRH agonist and antagonist. Similarly, kisspeptin expressing neurons are likely to mediate the well-established link between energy balance and reproductive functions. Exogenous kisspeptin can be used for physiological ovarian hyperstimulation for in-vitro fertilization. Moreover, kisspeptin antagonist therapy can be used for the treatment of postmenapousal women, precocious puberty, PCOS, endometriosis and uterine fibroids. In this review, we will analyze the central mechanisms involved in the integration of metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction. PMID:26074346

  12. Hierarchical organization of ferrocene-peptides.

    Science.gov (United States)

    Beheshti, Samaneh; Martić, Sanela; Kraatz, Heinz-Bernhard

    2012-07-16

    Hierarchical self-assembly of disubstituted ferrocene (Fc)-peptide conjugates that possess Gly-Val-Phe and Gly-Val-Phe-Phe peptide substituents leads to the formation of nano- and micro-sized assemblies. Hydrogen-bonding and hydrophobic interactions provide directionality to the assembly patterns. The self-assembling behavior of these compounds was studied in solution by using (1)H NMR and circular dichroism (CD) spectroscopies. In the solid state, attenuated total reflectance (ATR) FTIR spectroscopy, single-crystal X-ray diffraction (XRD), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) methods were used. Spontaneous self-assembly of Fc-peptides through intra- and intermolecular hydrogen-bonding interactions induces supramolecular assemblies, which further associate and give rise to fibers, large fibrous crystals, and twisted ropes. In the case of Fc[CO-Gly-Val-Phe-OMe](2) (1), molecules initially interact to form pleated sheets that undergo association into long fibers that form bundles and rectangular crystalline cuboids. Molecular offsets and defects, such as screw dislocations and solvent effects that occur during crystal growth, induce the formation of helical arrangements, ultimately leading to large twisted ropes. By contrast, the Fc-tetrapeptide conjugate Fc[CO-Gly-Val-Phe-Phe-OMe](2) (2) forms a network of nanofibers at the supramolecular level, presumably due to the additional hydrogen-bonding and hydrophobic interactions that stem from the additional Phe residues. PMID:22707407

  13. C-peptide and Diabetic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun Cai; Hui-qin Xu; Yi Lu

    2011-01-01

    With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive fimctions.Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system,hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide defidency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients.Those Findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

  14. Antimicrobial peptides in echinoderm host defense.

    Science.gov (United States)

    Li, Chun; Blencke, Hans-Matti; Haug, Tor; Stensvåg, Klara

    2015-03-01

    Antimicrobial peptides (AMPs) are important effector molecules in innate immunity. Here we briefly summarize characteristic traits of AMPs and their mechanisms of antimicrobial activity. Echinoderms live in a microbe-rich marine environment and are known to express a wide range of AMPs. We address two novel AMP families from coelomocytes of sea urchins: cysteine-rich AMPs (strongylocins) and heterodimeric AMPs (centrocins). These peptide families have conserved preprosequences, are present in both adults and pluteus stage larvae, have potent antimicrobial properties, and therefore appear to be important innate immune effectors. Strongylocins have a unique cysteine pattern compared to other cysteine-rich peptides, which suggests a novel AMP folding pattern. Centrocins and SdStrongylocin 2 contain brominated tryptophan residues in their native form. This review also includes AMPs isolated from other echinoderms, such as holothuroidins, fragments of beta-thymosin, and fragments of lectin (CEL-III). Echinoderm AMPs are crucial molecules for the understanding of echinoderm immunity, and their potent antimicrobial activity makes them potential precursors of novel drug leads.

  15. ANTIMICROBIAL PEPTIDES: AN EFFECTIVE ALTERNATIVE FOR ANTIBIOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    KK PULICHERLA

    2013-01-01

    Full Text Available Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence has suggested that cationic antimicrobial peptides (AMP’s are of greatest potential to represent a new class of antibiotics. These peptides have a good scope in current antibiotic research. During the past two decades several AMPs have been isolated from a wide variety of animals (both vertebrates and invertebrates, and plants as well as from bacteria and fungi. These are relatively small (<10kDa, cationic and amphipathic peptides of variable length, sequence and structure. These peptides exhibit broad-spectrum activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, protozoa, yeast, fungi and viruses. Most of these peptides are believed to act by disrupting the plasma membrane leading to the lysis of the cell. Antimicrobial peptides encompass a wide variety of structural motifs such as α -helical peptides, β -sheet peptides, looped peptides and extended peptides. Preparations enriched by a specific protein are rarely easily obtained from natural host cells. Hence, recombinant protein production is frequently the sole applicable procedure. Several fusion strategies have been developed for the expression and purification of small antimicrobial peptides (AMPs in recombinant bacterial expression systems which were produced by cloning. This article aims to review in brief the sources of antimicrobial peptides, diversity in structural features, mode of action, production strategies and insight into the current data on their antimicrobial activity followed by a brief comment on the peptides that have entered clinical trials.

  16. Stability of diphenylalanine peptide nanotubes in solution

    Science.gov (United States)

    Andersen, Karsten Brandt; Castillo-Leon, Jaime; Hedström, Martin; Svendsen, Winnie Edith

    2011-03-01

    Over the last couple of years, self-organizing nanotubes based on the dipeptide diphenylalanine have received much attention, mainly as possible building blocks for the next generation of biosensors and as drug delivery systems. One of the main reasons for this large interest is that these peptide nanotubes are believed to be very stable both thermally and chemically. Previously, the chemical and thermal stability of self-organizing structures has been investigated after the evaporation of the solvent. However, it was recently discovered that the stability of the structures differed significantly when the tubes were in solution. It has been shown that, in solution, the peptide nanotubes can easily be dissolved in several solvents including water. It is therefore of critical importance that the stability of the nanotubes in solution and not after solvent evaporation be investigated prior to applications in which the nanotube will be submerged in liquid. The present article reports results demonstrating the instability and suggests a possible approach to a stabilization procedure, which drastically improves the stability of the formed structures. The results presented herein provide new information regarding the stability of self-organizing diphenylalanine nanotubes in solution.Over the last couple of years, self-organizing nanotubes based on the dipeptide diphenylalanine have received much attention, mainly as possible building blocks for the next generation of biosensors and as drug delivery systems. One of the main reasons for this large interest is that these peptide nanotubes are believed to be very stable both thermally and chemically. Previously, the chemical and thermal stability of self-organizing structures has been investigated after the evaporation of the solvent. However, it was recently discovered that the stability of the structures differed significantly when the tubes were in solution. It has been shown that, in solution, the peptide nanotubes can

  17. Peptide and non-peptide opioid-induced hyperthermia in rabbits

    Science.gov (United States)

    Kandasamy, S. B.; Williams, B. A.

    1983-01-01

    The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl-normetazocine was found to induce hyperthermia in rabbits. The similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME), and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) was also found to cause hyperthermia. Results indicate that only the liver-like transport system is important to the ventricular inactivation of BE and DAME. Prostaglandins and norepinephrine were determined not to be involved in peptide and nonpeptide opioid-induced hyperthermia. In addition, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and nonpeptide opioids. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine, BE, ME, and DAME since naloxone attenuated them. However, the hyperthermic response to ketocyclazocine and N-allyl-normetazocine was not antagonized by naloxone.

  18. Review: Formation of Peptide Radical Ions Through Dissociative Electron Transfer in Ternary Metal-Ligand-Peptide Complexes

    International Nuclear Information System (INIS)

    The formation and fragmentation of odd-electron ions of peptides and proteins is of interest to applications in biological mass spectrometry. Gas-phase redox chemistry occurring during collision-induced dissociation of ternary metal-ligand-peptide complexes enables the formation of a variety of peptide radicals including the canonical radical cations, M+#smbullet#, radical dications, (M+H)2+#smbullet#, radical anions, (M-2H)-#smbullet#. In addition, odd-electron peptide ions with well-defined initial location of the radical site are produced through side chain losses from the radical ions. Subsequent fragmentation of these species provides information on the role of charge and the location of the radical site on the competition between radical-induced and proton-driven fragmentation of odd-electron peptide ions. This account summarizes current understanding of the factors that control the efficiency of the intramolecular electron transfer (ET) in ternary metal-ligand-peptide complexes resulting in formation of odd-electron peptide ions. Specifically, we discuss the effect of the metal center, the ligand and the peptide structure on the competition between the ET, proton transfer (PT), and loss of neutral peptide and neutral peptide fragments from the complex. Fundamental studies of the structures, stabilities, and the energetics and dynamics of fragmentation of such complexes are also important for detailed molecular-level understanding of photosynthesis and respiration in biological systems.

  19. Competition between bound and free peptides in an ELISA-based procedure that assays peptides derived from protein digests

    Directory of Open Access Journals (Sweden)

    Pace Umberto

    2006-05-01

    Full Text Available Abstract Background We describe an ELISA-based method that can be used to identify and quantitate proteins in biological samples. In this method, peptides in solution, derived from proteolytic digests of the sample, compete with substrate-attached synthetic peptides for antibodies, also in solution, generated against the chosen peptides. The peptides used for the ELISA are chosen on the basis of their being (i products of the proteolytic (e.g. tryptic digestion of the protein to be identified and (ii unique to the target protein, as far as one can know from the published sequences. Results In this paper we describe the competition assay and we define the optimal conditions for the most effective assay. We have performed an analysis of the kinetics of interaction between the four components of the assay: the plastic substratum to which the peptide is bound, the bound peptide itself, the competing added peptide, and the antibody that is specific for the peptide and we compare the results of theoretical simulations to the actual data in some model systems. Conclusion The data suggest that the peptides bind to the plastic substratum in more than one conformation and that, once bound, the peptide displays different affinities for the antibody, depending on how it has bound to the plate

  20. Mixed α/β-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability.

    Science.gov (United States)

    Mangelschots, Jeroen; Bibian, Mathieu; Gardiner, James; Waddington, Lynne; Van Wanseele, Yannick; Van Eeckhaut, Ann; Acevedo, Maria M Diaz; Van Mele, Bruno; Madder, Annemieke; Hoogenboom, Richard; Ballet, Steven

    2016-02-01

    Peptide hydrogels are a highly promising class of materials for biomedical application, albeit facing many challenges with regard to stability and tunability. Here, we report a new class of amphipathic peptide hydrogelators, namely mixed α/β-peptide hydrogelators. These mixed α/β-gelators possess good rheological properties (high storage moduli) and form transparent self-supporting gels with shear-thinning behavior. Infrared spectroscopy indicates the presence of β-sheets as the underlying secondary structure. Interestingly, self-assembled nanofibers of the mixed α/β-peptides display unique structural morphologies with alteration of the C-terminus (acid vs amide) playing a key role in the fiber formation and gelation properties of the resulting hydrogels. The incorporation of β3-homoamino acid residues within the mixed α/β-peptide gelators led to an increase in proteolytic stability of the peptides under nongelating conditions (in solution) as well as gelating conditions (as hydrogel). Under diluted conditions, degradation of mixed α/β-peptides in the presence of elastase was slowed down 120-fold compared to that of an α-peptide, thereby demonstrating beneficial enzymatic resistance for hydrogel applications in vivo. In addition, increased half-life values were obtained for the mixed α/β-peptides in human blood plasma, as compared to corresponding α-peptides. It was also found that the mixed α/β-peptides were amenable to injection via needles used for subcutaneous administrations. The preformed peptide gels could be sheared upon injection and were found to quickly reform to a state close to that of the original hydrogel. The shown properties of enhanced proteolytic stability and injectability hold great promise for the use of these novel mixed α/β-peptide hydrogels for applications in the areas of tissue engineering and drug delivery. PMID:26741458

  1. Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates

    DEFF Research Database (Denmark)

    Hansen, Anna Mette; Bonke, Gitte; Larsen, Camilla Josephine;

    2016-01-01

    Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge....... In the present study we show that antimicrobial peptides (AMPs) with an intracellular mode of action can be efficient vehicles for bacterial delivery of an antibacterial PNA targeting the essential acpP gene. The results demonstrate that buforin 2-A (BF2-A), drosocin, oncocin 10, Pep-1-K, KLW-9,13-a, (P59→W59...

  2. Peptide pool immunization and CD8+ T cell reactivity

    DEFF Research Database (Denmark)

    Rasmussen, Susanne B; Harndahl, Mikkel N; Buus, Anette Stryhn;

    2013-01-01

    Mice were immunized twice with a pool of five peptides selected among twenty 8-9-mer peptides for their ability to form stable complexes at 37°C with recombinant H-2K(b) (half-lives 10-15h). Vaccine-induced immunity of splenic CD8(+) T cells was studied in a 24h IFNγ Elispot assay. Surprisingly......, IFNγ spot-formation was observed without addition of peptide to the assay culture at 3 weeks and 3 months after immunization. To clarify if IFNγ spot formation in the absence of peptide exposure ex vivo is caused by the peptide-pool per se, mice were immunized with single peptides. Three of the five...

  3. Characterization of Selective Antibacterial Peptides by Polarity Index

    Directory of Open Access Journals (Sweden)

    C. Polanco

    2012-01-01

    Full Text Available In the recent decades, antibacterial peptides have occupied a strategic position for pharmaceutical drug applications and became subject of intense research activities since they are used to strengthen the immune system of all living organisms by protecting them from pathogenic bacteria. This work proposes a simple and easy statistical/computational method through a peptide polarity index measure by which an antibacterial peptide subgroup can be efficiently identified, that is, characterized by a high toxicity to bacterial membranes but presents a low toxicity to mammal cells. These peptides also have the feature not to adopt to an alpha-helicoidal structure in aqueous solution. The double-blind test carried out to the whole Antimicrobial Peptide Database (November 2011 showed an accuracy of 90% applying the polarity index method for the identification of such antibacterial peptide groups.

  4. Survey of small antifungal peptides with chemotherapeutic potential.

    Science.gov (United States)

    Desbois, Andrew P; Tschörner, David; Coote, Peter J

    2011-08-01

    Many cationic peptides with antimicrobial properties have been isolated from bacteria, fungi, plants, and animals. These peptides vary in molecular size, potency and spectra of activities. This report surveyed the literature to highlight the peptides that have antifungal activity and greatest potential for development as new therapeutic agents. Thus, to be included in the evaluation, each peptide had to fulfil the following criteria: (i) potent antifungal activity, (ii) no, or minimal, mammalian cell toxicity, (iii) of ≤25 amino acids in length, which minimises the costs of synthesis, reduces immunogenicity and enhances bioavailability and stability in vivo, (iv) minimal post-translational modifications (also reduces the production costs). The ~80 peptides that satisfied these criteria are discussed with respect to their structures, mechanisms of antimicrobial action and in vitro and in vivo toxicities. Certainly, some of these small peptides warrant further study and have potential for future exploitation as new antifungal agents. PMID:21470150

  5. Advances in Fmoc solid-phase peptide synthesis.

    Science.gov (United States)

    Behrendt, Raymond; White, Peter; Offer, John

    2016-01-01

    Today, Fmoc SPPS is the method of choice for peptide synthesis. Very-high-quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications. PMID:26785684

  6. Optimization of antibacterial peptides by genetic algorithms and cheminformatics

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Jenssen, Håvard; Cheung, Warren A.;

    2011-01-01

    47 of the top rated 50 peptides chosen from an in silico library of nearly 100 000 sequences. Here, we report a method of generating candidate peptide sequences using the heuristic evolutionary programming method of genetic algorithms (GA), which provided a large (19-fold) improvement...... in identification of novel antibacterial peptides. Approximately 0.50% of peptides evaluated during the GA method were classified as highly active, while only 0.026% of the nearly 100 000 sequences we previously screened were classified as highly active. A selection of these peptides was tested in vitro...... and activities reported here. While GA significantly improves the possibility of identifying candidate peptides, we encountered important pitfalls to this method that should be considered when using GA....

  7. Optimization of reversed-phase chromatography methods for peptide analytics.

    Science.gov (United States)

    Khalaf, Rushd; Baur, Daniel; Pfister, David

    2015-12-18

    The analytical description and quantification of peptide solutions is an essential part in the quality control of peptide production processes and in peptide mapping techniques. Traditionally, an important tool is analytical reversed phase liquid chromatography. In this work, we develop a model-based tool to find optimal analytical conditions in a clear, efficient and robust manner. The model, based on the Van't Hoff equation, the linear solvent strength correlation, and an analytical solution of the mass balance on a chromatographic column describing peptide retention in gradient conditions is used to optimize the analytical scale separation between components in a peptide mixture. The proposed tool is then applied in the design of analytical reversed phase liquid chromatography methods of five different peptide mixtures. PMID:26620597

  8. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant.

  9. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant. PMID:7895166

  10. Proinflammatory Effects of C-Peptide in Different Tissues

    Directory of Open Access Journals (Sweden)

    Dusica Vasic

    2012-01-01

    Full Text Available Atherosclerosis is well known as an inflammatory disease that can lead to clinical complications such as heart attack or stroke. C-peptide as a cleavage product of proinsulin is in the last few decades known as an active peptide with a number of different effects on microvascular and macrovascular complications in type 2 diabetic patients. Patients with insulin resistance and early type 2 diabetes show elevated levels of C-peptide in blood. Several last findings demonstrated deposition of C-peptide in the vessel wall in ApoE-deficient mice and induction of local inflammation. Besides that, C-peptide has proliferative effects on human mesangial cells. This review discusses recently published proinflammatory effects of C-peptide in different tissues.

  11. The binding mechanism of a peptidic cyclic serine protease inhibitor

    DEFF Research Database (Denmark)

    Jiang, Longguang; Svane, Anna Sigrid P.; Sørensen, Hans Peter;

    2011-01-01

    , have attracted considerable attention. Here, we have investigated the mechanism of binding of peptidic inhibitors to serine protease targets. Our model is upain-1 (CSWRGLENHRMC), a disulfide-bond-constrained competitive inhibitor of human urokinase-type plasminogen activator with a noncanonical......Serine proteases are classical objects for studies of catalytic and inhibitory mechanisms as well as interesting as therapeutic targets. Since small-molecule serine protease inhibitors generally suffer from specificity problems, peptidic inhibitors, isolated from phage-displayed peptide libraries...... is stabilised by intrapeptide contacts between the N-terminal extension and the core peptide around Trp3. These results provide a uniquely detailed description of the binding of a peptidic protease inhibitor to its target and are of general importance in the development of peptidic inhibitors with high...

  12. Interaction of peptides with cell membranes: insights from molecular modeling

    Science.gov (United States)

    Li, Zhen-lu; Ding, Hong-ming; Ma, Yu-qiang

    2016-03-01

    The investigation of the interaction of peptides with cell membranes is the focus of active research. It can enhance the understanding of basic membrane functions such as membrane transport, fusion, and signaling processes, and it may shed light on potential applications of peptides in biomedicine. In this review, we will present current advances in computational studies on the interaction of different types of peptides with the cell membrane. Depending on the properties of the peptide, membrane, and external environment, the peptide-membrane interaction shows a variety of different forms. Here, on the basis of recent computational progress, we will discuss how different peptides could initiate membrane pores, translocate across the membrane, induce membrane endocytosis, produce membrane curvature, form fibrils on the membrane surface, as well as interact with functional membrane proteins. Finally, we will present a conclusion summarizing recent progress and providing some specific insights into future developments in this field.

  13. Polymer-based vehicles for therapeutic peptide delivery.

    Science.gov (United States)

    Zhang, Jinjin; Desale, Swapnil S; Bronich, Tatiana K

    2015-01-01

    During the last decades increasing attention has been paid to peptides as potential therapeutics. However, clinical applications of peptide drugs suffer from susceptibility to degradation, rather short circulation half-life, limited ability to cross physiological barriers and potential immunogenicity. These challenges can be addressed by using polymeric materials as peptide delivery systems, owing to their versatile structures and properties. A number of polymer-based vehicles have been developed to stabilize the peptides and to control their release rates. Unfortunately, no single polymer or formulation strategy has been considered ideal for all types of peptide drugs. In this review, currently used and potential polymer-based systems for the peptide delivery will be discussed.

  14. Tumor Antigen-Derived Peptides Delivery for Cancer Immunotherapy.

    Science.gov (United States)

    Wenxue, Ma

    2014-02-05

    Tumor antigenic peptides therapeutics is a promising field for cancer immunotherapy. Benefits include the ease and rapid synthesis of antigenic peptides and capacity for modifications. In the past years, many peptide-based cancer vaccines have been tested in clinical trials with a limited success because of the difficulties associated with peptide stability and delivery approaches, consequently, resulting in inefficient antigen presentation and low response rates in patients with cancer. The development of suitable and efficient vaccine carrier systems still remains a major challenge. This article aims to describe a new delivery approach for tumor antigenic peptides and rationales of dendritic cells (DCs)-based vaccination. In order to elicit enhanced immune responses, poly(DL-lactide-co-glycolide) (PLGA), which has been approved by the US Food and Drug Administration (FDA) for the use of drug delivery, diagnostics and other applications of clinical and basic science research were employed for the formulation of making nanoparticles (NPs) while delivering tumor antigenic peptides.

  15. Peptide encapsulation regulated by the geometry of carbon nanotubes.

    Science.gov (United States)

    Zhang, Zhi-Sen; Kang, Yu; Liang, Li-Jun; Liu, Ying-Chun; Wu, Tao; Wang, Qi

    2014-02-01

    In this work the encapsulation of an α-helical peptide in single carbon nanotubes (CNTs) with similar diameter and length but different geometry (armchair and zigzag) was investigated through molecular dynamics simulations and free energy calculations. Our simulation results showed that in vacuo it makes no evident difference whether the investigated peptide is encapsulated in armchair or zigzag CNTs; however, in aqueous solution the armchair CNT encapsulates the peptide remarkably easier than the zigzag CNT does. A detailed analysis revealed that the equilibrium conformation of the water molecules inside the CNTs with varying geometry mediates the peptide encapsulation. It suggests that the water molecules play an important role in regulating behaviors of biomolecules in bio-systems. Then the impact of the CNT geometry on the conformational changes of the confined peptide was studied. Analyses of secondary structures showed the α-helix of the peptide could be better maintained in the zigzag CNT.

  16. The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics.

    Science.gov (United States)

    Escano, Jerome; Stauffer, Byron; Brennan, Jacob; Bullock, Monica; Smith, Leif

    2014-12-01

    Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that promotes the core peptide's interaction with the post translational modification (PTM) enzymes. Following PTMs, mutacin 1140 is transported out of the cell and the leader peptide is cleaved to yield the antibacterial peptide. Mutacin 1140 leader peptide is structurally unique compared to other class I lantibiotic leader peptides. Herein, we further our understanding of the structural differences of mutacin 1140 leader peptide with regard to other class I leader peptides. We have determined that the length of the leader peptide is important for the biosynthesis of mutacin 1140. We have also determined that mutacin 1140 leader peptide contains a novel four amino acid motif compared to related lantibiotics. PTM enzyme recognition of the leader peptide appears to be evolutionarily distinct from related class I lantibiotics. Our study on mutacin 1140 leader peptide provides a basis for future studies aimed at understanding its interaction with the PTM enzymes.

  17. Proinsulin C-peptide interferes with insulin fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Landreh, Michael [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden); Stukenborg, Jan-Bernd [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Willander, Hanna [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Soeder, Olle [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Johansson, Jan [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, S-751 23 Uppsala (Sweden); Joernvall, Hans, E-mail: Hans.Jornvall@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  18. Nonlinear Optical Properties of Triphenylalanine-based Peptide Nanostructures

    Science.gov (United States)

    Kudryavtsev, A. V.; Mishina, E. D.; Sigov, A. S.

    2016-05-01

    Nonlinear optical properties of peptide nanobelts and peptide nanospheres, the two types of self-assembled triphenylalanine-based peptide nanostructures, are studied. Nanobelts nonlinear susceptibility tensor components are evaluated, and nanobelts crystal structure and crystallographic orientation are defined on the basis of nonlinear optical mapping and polarization dependences of the second harmonic signal. The results obtained suggest that it is possible to use these materials as biologically compatible nonlinear optical converters.

  19. Development of New Tools for the Synthesis of "Difficult Peptides"

    OpenAIRE

    Paradís Bas, Marta

    2015-01-01

    Tesi realitzada a l'Institut de Recerca Biomèdica de Barcelona (IRBB) The known as "difficult peptides", as well as those sequences that aggregate in solution, are some of those molecules with high applicability as nanomaterials or even in medicine field. This thesis has addressed to overcome the synthetic, as well as, the peptide manipulation in solution drawbacks associated to this kind of peptides. The strategies proposed and evaluated in the present work have been divided in three chap...

  20. Targeting cyclin-dependent kinases in Drosophila with peptide aptamers

    OpenAIRE

    Kolonin, Mikhail G.; Finley, Russell L.

    1998-01-01

    Two-hybrid technology provides a simple way to isolate small peptide aptamers that specifically recognize and strongly bind to a protein of interest. These aptamers have the potential to dominantly interfere with specific activities of their target proteins and, therefore, could be used as in vivo inhibitors. Here we explore the ability to use peptide aptamers as in vivo inhibitors by expressing aptamers directed against cell cycle regulators in Drosophila. We expressed two peptide aptamers, ...

  1. Susceptibility to Infectious Diseases Based on Antimicrobial Peptide Production▿

    Science.gov (United States)

    Rivas-Santiago, Bruno; Serrano, Carmen J.; Enciso-Moreno, J. Antonio

    2009-01-01

    In the last few years, the great impact of antimicrobial peptides on infectious disease susceptibility and natural resistance has been reported. In some cases, susceptibility to diseases is related to antimicrobial peptide polymorphisms and gene copy numbers, but for the vast majority of infectious diseases, these phenomena need to be elucidated. This review is focused on the current knowledge about susceptibility and resistance conferred by genetic variations in antimicrobial peptide expression in infectious diseases. PMID:19703980

  2. Susceptibility to infectious diseases based on antimicrobial peptide production.

    Science.gov (United States)

    Rivas-Santiago, Bruno; Serrano, Carmen J; Enciso-Moreno, J Antonio

    2009-11-01

    In the last few years, the great impact of antimicrobial peptides on infectious disease susceptibility and natural resistance has been reported. In some cases, susceptibility to diseases is related to antimicrobial peptide polymorphisms and gene copy numbers, but for the vast majority of infectious diseases, these phenomena need to be elucidated. This review is focused on the current knowledge about susceptibility and resistance conferred by genetic variations in antimicrobial peptide expression in infectious diseases.

  3. Chemo-enzymatic peptide synthesis : bioprocess engineering aspects

    OpenAIRE

    Vossenberg, P.

    2012-01-01

      Peptides, in particular oligopeptides, play an important role in the fields of health care, nutrition and cosmetics. Chemical synthesis is currently the most mature technique for the synthesis of peptides that range in length from 5 to 80 amino acids. Chemical synthesis is, however, expected to be more and more combined with enzyme-catalyzed synthesis, resulting in chemo-enzymatic approaches towards peptide synthesis. The racemization that hampers chemical synthesis can be prevented by...

  4. Origination of the Protein Fold Repertoire from Oily Pluripotent Peptides

    OpenAIRE

    Mannige, Ranjan V.

    2014-01-01

    While the repertoire of protein folds that exists today underlies most of life’s capabilities, our mechanistic picture of protein fold origination is incomplete. This paper discusses a hypothetical mechanism for the emergence of the protein fold repertoire from highly dynamic and collapsed peptides, exemplified by peptides with high oil content or hydrophobicity. These peptides are called pluripotent to emphasize their capacity to evolve into numerous folds transiently available to them. As e...

  5. Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine

    OpenAIRE

    Cui, Chengji; Stevens, Vernon C.; Schwendeman, Steven P.

    2006-01-01

    Advanced contraceptive peptide vaccines suffer from the unavailability of adjuvants capable of enhancing the antibody response with acceptable safety. We sought to overcome this limitation by employing two novel poly(lactic-co-glycolic acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from tetanus toxoid, C-TT2-CTP35: surface-conjugated immunogen to induce phagocytosis; and encapsulated peptide ...

  6. Analysis of illegal peptide biopharmaceuticals frequently encountered by controlling agencies.

    Science.gov (United States)

    Vanhee, Celine; Janvier, Steven; Desmedt, Bart; Moens, Goedele; Deconinck, Eric; De Beer, Jacques O; Courselle, Patricia

    2015-09-01

    Recent advances in genomics, recombinant expression technologies and peptide synthesis have led to an increased development of protein and peptide therapeutics. Unfortunately this goes hand in hand with a growing market of counterfeit and illegal biopharmaceuticals, including substances that are still under pre-clinical and clinical development. These counterfeit and illegal protein and peptide substances could imply severe health threats as has been demonstrated by numerous case reports. The Belgian Federal Agency for Medicines and Health Products (FAMHP) and customs are striving, together with their global counterparts, to curtail the trafficking and distributions of these substances. At their request, suspected protein and peptide preparations are analysed in our Official Medicines Control Laboratory (OMCL). It stands to reason that a general screening method would be beneficiary in the battle against counterfeit and illegal peptide drugs. In this paper we present such general screening method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the identification of counterfeit and illegal injectable peptide preparations, extended with a subsequent quantification method using ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD). The screening method, taking only 30 min, is able to selectively detect 25 different peptides and incorporates the proposed minimum of five identification points (IP) as has been recommended for sports drug testing applications. The group of peptides represent substances which have already been detected in illegal and counterfeit products seized by different European countries as well as some biopharmaceutical peptides which have not been confiscated yet by the controlling agencies, but are already being used according to the many internet users forums. Additionally, we also show that when applying the same LC gradient, it is also possible to quantify these peptides without the need for

  7. Incorporation of peptides in phospholipid aggregates using ultrasound

    OpenAIRE

    Silva, Raquel; Little, Collin; Ferreira, Helena; Paulo, Artur Cavaco

    2008-01-01

    This study presents the highlights of ultrasonic effects on peptides incorporated on phospholipid aggregates (liposomes). These liposomes or vesicles are known as transport agents in skin drug delivery and for hair treatment. They might be a good model to deliver larger peptides into hair to restore fibre strength after hair coloration, modelling, permanent wave and/or straightening. The preparation of liposomes 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) with peptides (LLLLK LLLLK LL...

  8. IPG strip-based peptide fractionation for shotgun proteomics

    OpenAIRE

    Eravci, M.; Sommer, C; Selbach, M

    2014-01-01

    Efficient fractionation of peptides is an essential prerequisite for comprehensive analysis of complex protein mixtures by shotgun mass spectrometry. The separation of peptides by isoelectric focusing is particularly attractive due to its orthogonality to reverse-phase HPLC. Here, we present a protocol for in-gel peptide isoelectric focusing using immobilized pH gradient strips. The method shows high resolving power for up to 1 mg of sample and is highly reproducible.

  9. An Interplay between Electrostatic and Polar Interactions in Peptide Hydrogels

    OpenAIRE

    Joyner, Katherine; Taraban, Marc B; Feng, Yue; Yu, Y. Bruce

    2013-01-01

    Inherent chemical programmability available in peptide-based hydrogels has allowed diversity in the development of these materials for use in biomedical applications. Within the 20 natural amino acids, a range of chemical moieties are present. Here we used a mixing-induced self-assembly of two oppositely charged peptide modules to form a peptide-based hydrogel. To investigate electrostatic and polar interactions on the hydrogel, we replace amino acids from the negatively charged acidic glutam...

  10. Immunological half-life of porcine proinsulin C-peptide

    International Nuclear Information System (INIS)

    Immunological half-lifes of injected porcine C-peptide and insulin with RIA were studied and calculated as 9.8 and 8.0 minutes. Higher circulating levels of C-peptide as compared to insulin in normal young swines lead to speculation about a longer half-life of C-peptide. This hypothesis was verified in this study. Immunological half-lifes of porcine proinsulin and insulin in the pig were 20 and 6 minutes, respectively. (GSE)

  11. Proinsulin C-peptide interferes with insulin fibril formation

    International Nuclear Information System (INIS)

    Highlights: ► Insulin and C-peptide can interact under insulin fibril forming conditions. ► C-peptide is incorporated into insulin aggregates and alters aggregation lag time. ► C-peptide changes insulin fibril morphology and affects backbone accessibility. ► C-peptide may be a regulator of fibril formation by β-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic β-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  12. Analysis of Peptide Ligand Binding to FGFR1

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Simulating annealing algorithm was used in docking computation to predict a selected peptide VYMSPF(P2) binding site on the ectodomain of FGFR1. The peptide is located on the hydrophobic surface of the receptor, which is critical for FGF binding. The synthesized peptide can effectively inhibit the mitogenic activity of aFGF, and has a potential to become a therapeutic agent as an aFGF antagonist.

  13. Analysis of illegal peptide biopharmaceuticals frequently encountered by controlling agencies.

    Science.gov (United States)

    Vanhee, Celine; Janvier, Steven; Desmedt, Bart; Moens, Goedele; Deconinck, Eric; De Beer, Jacques O; Courselle, Patricia

    2015-09-01

    Recent advances in genomics, recombinant expression technologies and peptide synthesis have led to an increased development of protein and peptide therapeutics. Unfortunately this goes hand in hand with a growing market of counterfeit and illegal biopharmaceuticals, including substances that are still under pre-clinical and clinical development. These counterfeit and illegal protein and peptide substances could imply severe health threats as has been demonstrated by numerous case reports. The Belgian Federal Agency for Medicines and Health Products (FAMHP) and customs are striving, together with their global counterparts, to curtail the trafficking and distributions of these substances. At their request, suspected protein and peptide preparations are analysed in our Official Medicines Control Laboratory (OMCL). It stands to reason that a general screening method would be beneficiary in the battle against counterfeit and illegal peptide drugs. In this paper we present such general screening method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the identification of counterfeit and illegal injectable peptide preparations, extended with a subsequent quantification method using ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD). The screening method, taking only 30 min, is able to selectively detect 25 different peptides and incorporates the proposed minimum of five identification points (IP) as has been recommended for sports drug testing applications. The group of peptides represent substances which have already been detected in illegal and counterfeit products seized by different European countries as well as some biopharmaceutical peptides which have not been confiscated yet by the controlling agencies, but are already being used according to the many internet users forums. Additionally, we also show that when applying the same LC gradient, it is also possible to quantify these peptides without the need for

  14. Protein and lipid interactions of mammalian antibacterial peptides

    OpenAIRE

    Wang, Yuqin

    2001-01-01

    Gene-encoded antibacterial peptides are multifunctional effector molecules and play an important role in host innate immunity. Upon stimulation, the mature active peptides are released from inactive precursors. Cathelicidins constitute a family of antibacterial peptides, which share a conserved N-terminal cathelin-like region followed by a variable C-terminal antibacterial domain. In addition to its antibacterial activity, LL-37, the only cathelicidin found in human, is ...

  15. Interpretation of tandem mass spectra obtained from cyclic nonribosomal peptides.

    Science.gov (United States)

    Liu, Wei-Ting; Ng, Julio; Meluzzi, Dario; Bandeira, Nuno; Gutierrez, Marcelino; Simmons, Thomas L; Schultz, Andrew W; Linington, Roger G; Moore, Bradley S; Gerwick, William H; Pevzner, Pavel A; Dorrestein, Pieter C

    2009-06-01

    Natural and non-natural cyclic peptides are a crucial component in drug discovery programs because of their considerable pharmaceutical properties. Cyclosporin, microcystins, and nodularins are all notable pharmacologically important cyclic peptides. Because these biologically active peptides are often biosynthesized nonribosomally, they often contain nonstandard amino acids, thus increasing the complexity of the resulting tandem mass spectrometry data. In addition, because of the cyclic nature, the fragmentation patterns of many of these peptides showed much higher complexity when compared to related counterparts. Therefore, at the present time it is still difficult to annotate cyclic peptides MS/MS spectra. In this current work, an annotation program was developed for the annotation and characterization of tandem mass spectra obtained from cyclic peptides. This program, which we call MS-CPA is available as a web tool (http://lol.ucsd.edu/ms-cpa_v1/Input.py). Using this program, we have successfully annotated the sequence of representative cyclic peptides, such as seglitide, tyrothricin, desmethoxymajusculamide C, dudawalamide A, and cyclomarins, in a rapid manner and also were able to provide the first-pass structure evidence of a newly discovered natural product based on predicted sequence. This compound is not available in sufficient quantities for structural elucidation by other means such as NMR. In addition to the development of this cyclic annotation program, it was observed that some cyclic peptides fragmented in unexpected ways resulting in the scrambling of sequences. In summary, MS-CPA not only provides a platform for rapid confirmation and annotation of tandem mass spectrometry data obtained with cyclic peptides but also enables quantitative analysis of the ion intensities. This program facilitates cyclic peptide analysis, sequencing, and also acts as a useful tool to investigate the uncommon fragmentation phenomena of cyclic peptides and aids the

  16. Peptides Regulate Cortical Thymocytes Differentiation, Proliferation, and Apoptosis

    Directory of Open Access Journals (Sweden)

    V. Kh. Khavinson

    2011-01-01

    Full Text Available The processes of differentiation, proliferation, and apoptosis were studied in a cell culture of human cortical thymocytes under the influence of short peptides T-32 (Glu-Asp-Ala and T-38 (Lys-Glu-Asp. Peptides T-32 and T-38 amplified cortical thymocytes differentiation towards regulatory T cells, increased their proliferative activity, and decreased the level of apoptosis. Moreover, peptides under study stimulated proliferative and antiapoptotic activity of the mature regulatory T cells.

  17. Engineering β-sheet peptide assemblies for biomedical applications.

    Science.gov (United States)

    Yu, Zhiqiang; Cai, Zheng; Chen, Qiling; Liu, Menghua; Ye, Ling; Ren, Jiaoyan; Liao, Wenzhen; Liu, Shuwen

    2016-03-01

    Hydrogels have been widely studied in various biomedical applications, such as tissue engineering, cell culture, immunotherapy and vaccines, and drug delivery. Peptide-based nanofibers represent a promising new strategy for current drug delivery approaches and cell carriers for tissue engineering. This review focuses on the recent advances in the use of self-assembling engineered β-sheet peptide assemblies for biomedical applications. The applications of peptide nanofibers in biomedical fields, such as drug delivery, tissue engineering, immunotherapy, and vaccines, are highlighted. The current challenges and future perspectives for self-assembling peptide nanofibers in biomedical applications are discussed.

  18. Perspective of Use of Antiviral Peptides against Influenza Virus.

    Science.gov (United States)

    Skalickova, Sylvie; Heger, Zbynek; Krejcova, Ludmila; Pekarik, Vladimir; Bastl, Karel; Janda, Jozef; Kostolansky, Frantisek; Vareckova, Eva; Zitka, Ondrej; Adam, Vojtech; Kizek, Rene

    2015-10-01

    The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides. PMID:26492266

  19. Bioinspired peptide nanotubes: Deposition technology and physical properties

    International Nuclear Information System (INIS)

    Proteins and peptides have the intrinsic ability to self-assemble into elongated solid nanofibrils, which give rise to amyloid progressive neurodegenerative diseases (Alzheimer's, Parkinson, etc.). It has been found that of the core recognition motif of Aβ peptide is the diphenylalanine element. The diphenylalanine peptide can self-assemble into well-ordered peptide nanotubes (PNT). In this paper we report on our newly developed process-vapor deposition of PNT and 'bottom-up' nanotechnological techniques of PNT patterning. Study of several physical properties of PNT such as optical and electrochemical are presented. The results may lead to the development of a new generation of PNT-based bioinspired functional nanodevices.

  20. Method for predicting peptide detection in mass spectrometry

    Science.gov (United States)

    Kangas, Lars [West Richland, WA; Smith, Richard D [Richland, WA; Petritis, Konstantinos [Richland, WA

    2010-07-13

    A method of predicting whether a peptide present in a biological sample will be detected by analysis with a mass spectrometer. The method uses at least one mass spectrometer to perform repeated analysis of a sample containing peptides from proteins with known amino acids. The method then generates a data set of peptides identified as contained within the sample by the repeated analysis. The method then calculates the probability that a specific peptide in the data set was detected in the repeated analysis. The method then creates a plurality of vectors, where each vector has a plurality of dimensions, and each dimension represents a property of one or more of the amino acids present in each peptide and adjacent peptides in the data set. Using these vectors, the method then generates an algorithm from the plurality of vectors and the calculated probabilities that specific peptides in the data set were detected in the repeated analysis. The algorithm is thus capable of calculating the probability that a hypothetical peptide represented as a vector will be detected by a mass spectrometry based proteomic platform, given that the peptide is present in a sample introduced into a mass spectrometer.

  1. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  2. Developing a Dissociative Nanocontainer for Peptide Drug Delivery

    Directory of Open Access Journals (Sweden)

    Patrick Kelly

    2015-10-01

    Full Text Available The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

  3. Affinity purification of copper chelating peptides from chickpea protein hydrolysates.

    Science.gov (United States)

    Megías, Cristina; Pedroche, Justo; Yust, Maria M; Girón-Calle, Julio; Alaiz, Manuel; Millan, Francisco; Vioque, Javier

    2007-05-16

    Chickpea protein hydrolysates obtained with alcalase and flavourzyme were used for purification of copper chelating peptides by affinity chromatography using copper immobilized on solid supports. The chelating activity of purified peptides was indirectly measured by the inhibition of beta-carotene oxidation in the presence of copper. Two protein hydrolysates, obtained after 10 and 100 min of hydrolysis, were the most inhibitory of beta-carotene oxidation. Purified copper chelating peptides from these protein hydrolysates contained 19.7 and 35.1% histidine, respectively, in comparison to 2.7 and 2.6% in the protein hydrolysates. Chelating peptides from hydrolysate obtained after 10 min of hydrolysis were the most antioxidative being 8.3 times more antioxidative than the hydrolysate, while chelating peptides purified from protein hydrolysate obtained after 100 min were 3.1 times more antioxidative than its hydrolysate. However, the histidine content was higher in peptides derived from the 100 min hydrolysate (19.7 against 35.1% in 10 min hydrolysate), indicating that this amino acid is not the only factor involved in the antioxidative activity, and other factors such as peptide size or amino acid sequence are also determinant. This manuscript shows that affinity chromatography is a useful procedure for purification of copper chelating peptides. This method can be extended to other metals of interest in nutrition, such as calcium, iron, or zinc. Purified chelating peptides, in addition to their antioxidative properties, may also be useful in food mineral fortification for increasing the bioavailability of these metals.

  4. Effective Design of Multifunctional Peptides by Combining Compatible Functions.

    Science.gov (United States)

    Diener, Christian; Garza Ramos Martínez, Georgina; Moreno Blas, Daniel; Castillo González, David A; Corzo, Gerardo; Castro-Obregon, Susana; Del Rio, Gabriel

    2016-04-01

    Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf.

  5. Peptide antibiotics: holy or heretic grails of innate immunity?

    Science.gov (United States)

    Boman, H G

    1996-05-01

    In the last 2 years (1994-95), two symposium volumes and three reviews have been published that were fully devoted to peptide antibiotics (antibacterial peptides or antimicrobial peptides). Since the field has been growing rapidly, this review is largely a follow-up of new results published in the last 2 years. Sequencing of the 16S RNA of the small ribosomal subunit indicate that the microbial world is much larger than generally appreciated. The importance of the natural flora is stressed and its effect on the evolution of peptide antibiotics and immunity in general is discussed.

  6. Natriuretic pro-peptides in idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Skau, Maren Cecilie Kloppenbor; Gøtze, Jens Peter; Rehfeld, Jens F.;

    2010-01-01

    Idiopathic intracranial hypertension is a disorder of unknown pathogenesis. Natriuretic peptides may be involved in intracranial pressure regulation, but cerebrospinal fluid (CNS) and plasma concentrations in this disorder are unknown. We evaluated venous and intrathecal concentrations of ANP, BNP...... and CNP precursor peptides in 40 patients with idiopathic intracranial hypertension and in 20 controls. Natriuretic pro-peptides were quantitated using processing-independent assays. In CSF, no differences in peptide concentrations between patients and controls were found (proANP: 239 + or - 23 vs 231...

  7. Differential self-assembly behaviors of cyclic and linear peptides.

    Science.gov (United States)

    Choi, Sung-ju; Jeong, Woo-jin; Kang, Seong-Kyun; Lee, Myongsoo; Kim, Eunhye; Ryu, Du Yeol; Lim, Yong-beom

    2012-07-01

    Here we ask the fundamental questions about the effect of peptide topology on self-assembly. The study revealed that the self-assembling behaviors of cyclic and linear peptides are significantly different in several respects, in addition to sharing several similarities. Their clear differences included the morphological dissimilarities of the self-assembled nanostructures and their thermal stability. The similarities include their analogous critical aggregation concentration values and cytotoxicity profiles, which are in fact closely related. We believe that understanding topology-dependent self-assembly behavior of peptides is important for developing tailor-made self-assembled peptide nanostructures.

  8. Bioactive Peptides from Muscle Sources: Meat and Fish

    Directory of Open Access Journals (Sweden)

    Catherine Stanton

    2011-08-01

    Full Text Available Bioactive peptides have been identified in a range of foods, including plant, milk and muscle, e.g., beef, chicken, pork and fish muscle proteins. Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an outline of the bioactive peptides identified in the muscle protein of meat to date, with a focus on muscle protein from domestic animals and fish. The majority of research on bioactives from meat sources has focused on angiotensin-1-converting enzyme (ACE inhibitory and antioxidant peptides.

  9. Peptide Formation Mechanism on Montmorillonite Under Thermal Conditions

    Science.gov (United States)

    Fuchida, Shigeshi; Masuda, Harue; Shinoda, Keiji

    2014-02-01

    The oligomerization of amino acids is an essential process in the chemical evolution of proteins, which are precursors to life on Earth. Although some researchers have observed peptide formation on clay mineral surfaces, the mechanism of peptide bond formation on the clay mineral surface has not been clarified. In this study, the thermal behavior of glycine (Gly) adsorbed on montmorillonite was observed during heating experiments conducted at 150 °C for 336 h under dry, wet, and dry-wet conditions to clarify the mechanism. Approximately 13.9 % of the Gly monomers became peptides on montmorillonite under dry conditions, with diketopiperazine (cyclic dimer) being the main product. On the other hand, peptides were not synthesized in the absence of montmorillonite. Results of IR analysis showed that the Gly monomer was mainly adsorbed via hydrogen bonding between the positively charged amino groups and negatively charged surface sites (i.e., Lewis base sites) on the montmorillonite surface, indicating that the Lewis base site acts as a catalyst for peptide formation. In contrast, peptides were not detected on montmorillonite heated under wet conditions, since excess water shifted the equilibrium towards hydrolysis of the peptides. The presence of water is likely to control thermodynamic peptide production, and clay minerals, especially those with electrophilic defect sites, seem to act as a kinetic catalyst for the peptide formation reaction.

  10. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    Science.gov (United States)

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  11. PeptideMine - A webserver for the design of peptides for protein-peptide binding studies derived from protein-protein interactomes

    Directory of Open Access Journals (Sweden)

    Gopal Balasubramanian

    2010-09-01

    Full Text Available Abstract Background Signal transduction events often involve transient, yet specific, interactions between structurally conserved protein domains and polypeptide sequences in target proteins. The identification and validation of these associating domains is crucial to understand signal transduction pathways that modulate different cellular or developmental processes. Bioinformatics strategies to extract and integrate information from diverse sources have been shown to facilitate the experimental design to understand complex biological events. These methods, primarily based on information from high-throughput experiments, have also led to the identification of new connections thus providing hypothetical models for cellular events. Such models, in turn, provide a framework for directing experimental efforts for validating the predicted molecular rationale for complex cellular processes. In this context, it is envisaged that the rational design of peptides for protein-peptide binding studies could substantially facilitate the experimental strategies to evaluate a predicted interaction. This rational design procedure involves the integration of protein-protein interaction data, gene ontology, physico-chemical calculations, domain-domain interaction data and information on functional sites or critical residues. Results Here we describe an integrated approach called "PeptideMine" for the identification of peptides based on specific functional patterns present in the sequence of an interacting protein. This approach based on sequence searches in the interacting sequence space has been developed into a webserver, which can be used for the identification and analysis of peptides, peptide homologues or functional patterns from the interacting sequence space of a protein. To further facilitate experimental validation, the PeptideMine webserver also provides a list of physico-chemical parameters corresponding to the peptide to determine the feasibility of

  12. Peptide imprinted receptors for the determination of the small cell lung cancer associated biomarker progastrin releasing peptide

    DEFF Research Database (Denmark)

    Qader, A. A.; Urraca, J.; Torsetnes, S. B.;

    2014-01-01

    prior to LCMS based quantification. Peptide imprinted polymers with the best affinity characteristics were first identified from a 96-polymer combinatorial library. The effects of functional monomers, crosslinker, porogen, and template on adsorption capacity and selectivity for NLLGLIEAK were......Peptide imprinted polymers were developed for detection of progastrin releasing peptide (ProGRP); a low abundant blood based biomarker for small cell lung cancer. The polymers targeted the proteotypic nona-peptide sequence NLLGLIEAK and were used for selective enrichment of the proteotypic peptide...... investigated and optimized. Ultimately, a solid phase extraction method was developed for highly selective enrichment of the target peptide from tryptic digests. (C) 2014 Elsevier B.V. All rights reserved....

  13. From antimicrobial to anticancer peptides. A review.

    Directory of Open Access Journals (Sweden)

    Diana eGaspar

    2013-10-01

    Full Text Available Antimicrobial peptides (AMPs are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective and more efficient drugs is evident. Even though ACPs are expected to be selective towards tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides’ structure, modes of action, selectivity and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity towards specific cells while reducing toxicity are also discussed.

  14. Peptide synthesis under Enceladus hydrothermal condition

    Science.gov (United States)

    Fujishima, Kosuke; Takano, Yoshinori; Takai, Ken; Takahagi, Wataru; Adachi, Keito; Shibuya, Takazo; Tomita, Masaru

    2016-07-01

    Enceladus is one of the moons of Saturn, and it has been known to harbor interior ocean beneath the icy crust. The mass spectrometry data obtained by Cassini spacecraft indicates the presence of salty, and most likely alkaline ocean containing various organic compounds. While geochemical and other radiation related processes for in situ production of organics remain elusive, thermally unaltered carbonaceous chondrites, consisting the main body of Enceladus are known to be enriched with organic matters potentially including the building blocks of life (e.g., amino acids and amino acid precursors). Assuming that abiotic amino acids exist in the Enceladus alkaline seawater, we hypothesized that water-rock interaction may contribute to condensation of localized amino acids leading to peptide formation. In order to test this hypothesis, we have developed the Enceladus hydrothermal reactor based on the chemical constraints obtained through previous experimental and theoretical studies. We have added six different amino acids and introduced a thermal fluctuation system simulating the periodic tidal heating of the interior chondritic core. Total, eight sea water samples were obtained over the course of 147 days of experiment. While detection of peptide using Capillary Electrophoresis Time-of-Flight Mass Spectrometry (CE-TOF/MS) is still at the preliminary stage, so far pH monitoring and H2 and CO2 Gas Chromatography Mass Spectrometry (GC-MS) data clearly indicated the occurrence of serpentinization/carbonation reaction. Here, we discuss the interaction between aqueous alteration reactions and thermal cycling processes for the role of abiotic peptide formation under the Enceladus hydrothermal condition.

  15. Antimalarial Activity of Ultra-Short Peptides

    Directory of Open Access Journals (Sweden)

    María Yolanda Rios

    2009-12-01

    Full Text Available Ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. On the basis of the IC50 data for these compounds, the effects of nature, polarity, and amino acid sequence on Plasmodium berghei schizont cultures were analyzed too. Tetrapeptides Phe-Orn-Phe-Orn (4 and Lys-Phe-Phe-Orn (5 showed a very important activity with IC50 values of 3.31 and 2.57 μM, respectively. These two tetrapeptides are candidates for subsequent in vivo assays and SARS investigations.

  16. α-Peptide/ß-Peptoid Chimeras

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Bonke, Gitte; Vedel, Line;

    2007-01-01

    We describe the synthesis and characterization of the first generation of oligomers consisting of alternating repeats of a-amino acids and chiral N-alkyl-ß-alanine (ß-peptoid) residues. These chimeras are stable toward proteolysis, non-hemolytic, and possess antibacterial activity comparable to...... well-known antimicrobial agents. Moreover, the chimeras exhibit length-dependent, concentration-dependent, solvent-dependent, and ion-strength-dependent ellipticity, indicating the presence of a secondary structure in solution. Thus, a-peptide/ß-peptoid oligomers represent a promising novel...

  17. Hepcidin, a new iron regulatory peptide.

    Science.gov (United States)

    Nicolas, Gaël; Viatte, Lydie; Bennoun, Myriam; Beaumont, Carole; Kahn, Axel; Vaulont, Sophie

    2002-01-01

    Maintaining normal iron homeostasis is essential for the organism, as both iron deficiency and iron excess are associated with cellular dysfunction. Recently, several lines of evidence have suggested that hepcidin, a peptide mainly produced by the liver, plays a major role in the control of body iron homeostasis. The subject of this paper is to summarize the advances toward the understanding of function and regulation of hepcidin in iron metabolism and to provide new data on the regulation of hepcidin gene expression by erythropoietin, the major regulator of mammalian erythropoiesis. PMID:12547223

  18. Plant antimicrobial peptides as potential anticancer agents.

    Science.gov (United States)

    Guzmán-Rodríguez, Jaquelina Julia; Ochoa-Zarzosa, Alejandra; López-Gómez, Rodolfo; López-Meza, Joel E

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  19. Protein-peptide interactions in mixtures of whey peptides and whey proteins

    NARCIS (Netherlands)

    Creusot, N.; Gruppen, H.

    2007-01-01

    The effects of several conditions on the amounts and compositions of aggregates formed in mixtures of whey protein hydrolysate, made with Bacillus licheniformis protease, and whey protein isolate were investigated using response surface methodology. Next, the peptides present in the aggregates were

  20. Novel Zn2+-chelating peptides selected from a fimbria-displayed random peptide library

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Schembri, Mark; Klemm, Per

    2001-01-01

    The display of peptide sequences on the surface of bacteria is a technology that offers exciting applications in biotechnology and medical research. Type 1 fimbriae are surface organelles of Escherichia coli which mediate D-mannose-sensitive binding to different host surfaces by virtue of the Fim...

  1. Importance of Tryptophan in Transforming an Amphipathic Peptide into a Pseudomonas aeruginosa-Targeted Antimicrobial Peptide.

    Directory of Open Access Journals (Sweden)

    Xin Zhu

    Full Text Available Here, we found that simple substitution of amino acids in the middle position of the hydrophobic face of an amphipathic peptide RI16 with tryptophan (T9W considerably transformed into an antimicrobial peptide specifically targeting Pseudomonas aeruginosa. Minimal inhibitory concentration (MIC results demonstrated that T9W had a strong and specifically antimicrobial activity against P. aeruginosa, including antibiotic-resistant strains, but was not active against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Staphyfococcus epidermidis. Fluorescent spectroscopic assays indicated that T9W interacted with the membrane of P. aeruginosa, depolarizing the outer and the inner membrane of bacterial cells. Salt susceptibility assay showed that T9W still maintained its strong anti-pseudomonas activity in the presence of salts at physiological concentrations, and in hemolytic and MTT assays T9W also showed no toxicity against human blood cells and macrophages. In vivo assay demonstrated that T9W also displayed no toxicity to Chinese Kun Ming (KM mice. Furthermore, the strong antibiofilm activity was also observed with the peptide T9W, which decreased the percentage of biomass formation in a dose-dependent manner. Overall, these findings indicated that design of single-pathogen antimicrobial agents can be achieved by simple amino acid mutation in naturally occurring peptide sequences and this study suggested a model of optimization/design of anti-pseudomonas drugs in which the tryptophan residue was a conserved element.

  2. A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

    Directory of Open Access Journals (Sweden)

    Carvalho K.M.

    1999-01-01

    Full Text Available A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11 and angiotensin-converting enzyme (EC 3.4.15.1, respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM and for atrial natriuretic peptide (Km = 5 µM suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.

  3. Identification of renal natriuretic peptide receptor subpopulations by use of the non-peptide antagonist, HS-142-1.

    OpenAIRE

    Rutherford, R A; Matsuda, Y; Wilkins, M R; Polak, J M; Wharton, J

    1994-01-01

    1. The renal actions of natriuretic peptides are dictated by the distribution of guanylyl cyclase-linked (NPRA and NPRB) and non-guanylyl cyclase-linked (NPRC) receptors. Natriuretic peptide receptors have previously been distinguished on the basis of their differential affinity for peptide fragments and analogues; however, most of the available ligands are not fully selective. We have used the specific guanylyl cyclase-linked receptor antagonist, HS-142-1, to investigate the differential dis...

  4. Synergy between a collagen IV mimetic peptide and a somatotropin-domain derived peptide as angiogenesis and lymphangiogenesis inhibitors

    OpenAIRE

    Koskimaki, Jacob E.; Lee, Esak; Chen, William; Rivera, Corban G.; Rosca, Elena V.; Pandey, Niranjan B.; Popel, Aleksander S.

    2012-01-01

    Angiogenesis is central to many physiological and pathological processes. Here we show two potent bioinformatically-identified peptides, one derived from collagen IV and translationally optimized, and one from a somatotropin domain-containing protein, synergize in angiogenesis and lymphangiogenesis assays including cell adhesion, migration and in vivo Matrigel plugs. Peptide-peptide combination therapies have recently been applied to diseases such as human immunodeficiency virus (HIV), but re...

  5. Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers

    Science.gov (United States)

    Rexeisen, Emilie Lynn

    Many therapeutic strategies incorporate peptides into their designs to mimic the natural protein ligands found in vivo. A few examples are the short peptide sequences RGD and PHSRN that mimic the primary and synergy-binding domains of the extracellular matrix protein, fibronectin, which is recognized by the cell surface receptor, alpha5beta 1 integrin. Even though scaffold modification with biomimetic peptides remains one of the most promising approaches for tissue engineering, the use of these peptides in therapeutic tissue-engineered products and drug delivery systems available on the commercial market is limited because the peptides are not easily able to mimic the natural protein. The design of a peptide that can effectively target the alpha5beta1 integrin would greatly increase biomimetic scaffold therapeutic potential. A novel peptide containing both the RGD primary binding domain and PHSRN synergy-binding domain for fibronectin joined with the appropriate linker should bind alpha 5beta1 integrin more efficiently and lead to greater cell adhesion over RGD alone. Several fibronectin mimetic peptides were designed and coupled to dialkyl hydrocarbon tails to make peptide-amphiphiles. The peptides contained different linkers connecting the two binding domains and different spacers separating the hydrophobic tails from the hydrophilic headgroups. The peptide-amphiphiles were deposited on mica substrates using the Langmuir-Blodgett technique. Langmuir isotherms indicated that the peptide-amphiphiles that contained higher numbers of serine residues formed a more tightly packed monolayer, but the increased number of serines also made transferring the amphiphiles to the mica substrate more difficult. Atomic force microscopy (AFM) images of the bilayers showed that the headgroups might be bent, forming small divots in the surface. These divots may help expose the PHSRN synergy-binding domain. Parallel studies undertaken by fellow group members showed that human

  6. Multifunctional hybrid networks based on self assembling peptide sequences

    Science.gov (United States)

    Sathaye, Sameer

    The overall aim of this dissertation is to achieve a comprehensive correlation between the molecular level changes in primary amino acid sequences of amphiphilic beta-hairpin peptides and their consequent solution-assembly properties and bulk network hydrogel behavior. This has been accomplished using two broad approaches. In the first approach, amino acid substitutions were made to peptide sequence MAX1 such that the hydrophobic surfaces of the folded beta-hairpins from the peptides demonstrate shape specificity in hydrophobic interactions with other beta-hairpins during the assembly process, thereby causing changes to the peptide nanostructure and bulk rheological properties of hydrogels formed from the peptides. Steric lock and key complementary hydrophobic interactions were designed to occur between two beta-hairpin molecules of a single molecule, LNK1 during beta-sheet fibrillar assembly of LNK1. Experimental results from circular dichroism, transmission electron microscopy and oscillatory rheology collectively indicate that the molecular design of the LNK1 peptide can be assigned the cause of the drastically different behavior of the networks relative to MAX1. The results indicate elimination or significant reduction of fibrillar branching due to steric complementarity in LNK1 that does not exist in MAX1, thus supporting the original hypothesis. As an extension of the designed steric lock and key complementarity between two beta-hairpin molecules of the same peptide molecule. LNK1, three new pairs of peptide molecules LP1-KP1, LP2-KP2 and LP3-KP3 that resemble complementary 'wedge' and 'trough' shapes when folded into beta-hairpins were designed and studied. All six peptides individually and when blended with their corresponding shape complement formed fibrillar nanostructures with non-uniform thickness values. Loose packing in the assembled structures was observed in all the new peptides as compared to the uniform tight packing in MAX1 by SANS analysis. This

  7. Targeted delivery of an antigenic peptide to the endoplasmic reticulum: application for development of a peptide therapy for ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Hui-Chun Yu

    Full Text Available The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27. HLA-B27 heavy chain (HC has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC2. Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His6-ubiquitin-tagged Tat-derived peptide (THU can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS.

  8. Pulling peptides across nanochannels: resolving peptide binding and translocation through the hetero-oligomeric channel from Nocardia farcinica.

    Science.gov (United States)

    Singh, Pratik Raj; Bárcena-Uribarri, Iván; Modi, Niraj; Kleinekathöfer, Ulrich; Benz, Roland; Winterhalter, Mathias; Mahendran, Kozhinjampara R

    2012-12-21

    We investigated translocation of cationic peptides through nanochannels derived from the Gram-positive bacterium Nocardia farcinica at the single-molecule level. The two subunits NfpA and NfpB form a hetero-oligomeric cation selective channel. On the basis of amino acid comparison we performed homology modeling and obtained a channel structurally related to MspA of Mycobacterium smegmatis. The quantitative single-molecule measurements provide an insight into transport processes of solutes through nanochannels. High-resolution ion conductance measurements in the presence of peptides of different charge and length revealed the kinetics of peptide binding. The observed asymmetry in peptide binding kinetics indicated a unidirectional channel insertion in the lipid bilayer. In the case of cationic peptides, the external voltage acts as a driving force that promotes the interaction of the peptide with the channel surface. At low voltage, the peptide just binds to the channel, whereas at higher voltage, the force is strong enough to pull the peptide across the channel. This allows distinguishing quantitatively between peptide binding and translocation through the channel. PMID:23121560

  9. The Combination of Salt Induced Peptide Formation Reaction and Clay Catalysis: A Way to Higher Peptides under Primitive Earth Conditions

    Science.gov (United States)

    Rode, Bernd M.; Son, Hoang L.; Suwannachot, Yuttana; Bujdak, Juraj

    1999-05-01

    Two reactions with suggested prebiotic relevance for peptide evolution, the saltinduced peptide formation reaction and the peptide chain elongation/stabilization on clay minerals have been combined in experimental series starting from dipeptides and dipeptide/amino acid mixtures. The results show that both reactions can take place simultaneously in the same reaction environment and that the presence of mineral catalysts favours the formation of higher oligopeptides. These findings lend further support to the relevance of these reactions for peptide evolution on the primitive earth. The detailed effects of the specific clay mineral depend both on the nature of the mineral and the reactants in solution.

  10. Construction of HLA/Peptide Tetramer with Peptide-Linked β2 Microglobulin

    Institute of Scientific and Technical Information of China (English)

    沈传来; ChienchungCHANG; 张建琼; 郭薇; 孟凡岩; 谢维

    2004-01-01

    Analysis of the frequency of antigen-specific cytotoxic T lymphocytes (CTLs) ex vivo is largely dependent on the use of MHC/peptide tetramers. However, the latter reagents have not been widely available, most likely because of their costly and time-consuming production. In this report we utilized an economic strategy to construct HLA/peptide tetramers with recombinant peptide-linked β2 microglobulin (β2m). The HLA-A2-restricted, melanoma antigen MARTl-derived peptide MARTI27-35 (AAGIGILTV) was fused to the N terminus of human β2m through a 15-amino acid (aa)-long linker before being refolded with the recombinant biotinylated HLA-A2 heavy chain ectodomain. The resulted 2-component (2C) monomer was then tetramerized with phycoerythin-labeled streptavidin. The experimental result showed that the 2C HLA-A2/MARTI27-35 monomer was shown to bind to the HLA class Ⅰ complex-specific monoclonal antibody W6/32 and the HLA-A2/MARTI27-35 complex-specific single chain antibody fragment (scFv) 8.3, suggesting the correctness of its specificity. Furthermore, the 2C HLA-A2/MARTI27-35 tetramer detected a specific CD8+ T cell population in HLA-A2-restricted melanoma infiltrating lymphocytes as the conventional 3C HLA-A2/MARTI27-35 tetramer. The yield of 2C HLA-A2/MARTI27-35 monomerwas 2.5 times more than that of the conventional 3C monomer. Taken together, these data indicate that the HLA-A2/MARTI27-35 tetramer can be generated conveniently through the use of MARTI27-35 peptide-β2m fusion proteins, which can facilitate the monitoring of HLA-A2-restricted, MARTl-specific CTL responses in patients with melanoma.

  11. [Peptide synthesis aiming at elucidation and creation of protein functions].

    Science.gov (United States)

    Futaki, S

    1998-11-01

    The recent development of molecular biology has been elucidating outlines of the cross-talk of biomolecules. The understanding of the function of these biomolecules from the viewpoint of chemistry is now demanded not only for the understanding of biological systems but also for the creation of novel functional molecules. Here two topics are described about peptide synthesis aiming at the elucidation and the creation of protein functions. The first topic is the development of approaches for the synthesis of Tyr (SO3H)-containing peptides. Tyrosine sulfation is one of the most popular protein post-translational modifications. Synthetic peptides are of great help for the elucidation of the biological significance of tyrosine sulfation. We have developed two approaches for the efficient synthesis of tyrosine sulfate [Tyr (SO3H)]-containing peptides. The first approach employs a dimethylformamide-sulfur trioxide (DMF-SO3) complex as a sulfating agent and safety-catch protecting groups for the selective sulfation of tyrosine in the presence of serine. The second approach employs the direct introduction of Tyr(SO3H) into the peptide chain in the form of Fmoc-Tyr(SO3Na) followed by deprotection at 4 degrees C in trifluoroacetic acid. These approaches were successfully applied for the synthesis of cholecystokinin (CCK)-related peptides. The second topic deals with new approaches for the creation of artificial proteins through assembling alpha-helical peptides via selective disulfide or thioether formation. Approaches to assemble individual peptide segments on a peptide template were also developed. Four peptides corresponding to the transmembrane segments of the sodium channel (S4 in repeat I-IV) were assembled on a peptide template to give a protein having ion channel activity with rectification.

  12.  Pleiotropic action of proinsulin C-peptid

    Directory of Open Access Journals (Sweden)

    Michał Usarek

    2012-03-01

    Full Text Available  Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na /K -ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.

  13. Computational Design of Peptide Ligands for Ochratoxin A

    Directory of Open Access Journals (Sweden)

    Meike Heurich

    2013-06-01

    Full Text Available In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA. A virtual library of 20 natural amino acids was used as building blocks to design a short peptide library against ochratoxin A template using the de novo design program, LeapFrog, and the dynamic modelling software, FlexiDock. Peptide sequences were ranked according to calculated binding scores in their capacity to bind to ochratoxin A. Two high scoring peptides with the sequences N'-Cys-Ser-Ile-Val-Glu-Asp-Gly-Lys-C' (octapeptide and N'-Gly-Pro-Ala-Gly-Ile-Asp-Gly-Pro-Ala-Gly-Ile-Arg-Cys-C' (13-mer were selected for synthesis from the resulting database. These synthesized peptides were characterized using a microtitre plate-based binding assay and a surface plasmon resonance biosensor (Biacore 3000. The binding assay confirmed that both de novo designed peptides did bind to ochratoxin A in vitro. SPR analysis confirmed that the peptides bind to ochratoxin A, with calculated KD values of ~15.7 μM (13-mer and ~11.8 μM (octamer. The affinity of the peptides corresponds well with the molecular modelling results, as the 13-mer peptide affinity is about 1.3-times weaker than the octapeptide; this is in accordance with the binding energy values modelled by FlexiDock. This work illustrates the potential of using computational modelling to design a peptide sequence that exhibits in vitro binding affinity for a small molecular weight toxin.

  14. Novel antifungal peptides from Ceylon spinach seeds.

    Science.gov (United States)

    Wang, H; Ng, T B

    2001-11-01

    Two novel antifungal peptides, designated alpha- and beta-basrubrins, respectively, were isolated from seeds of the Ceylon spinach Basella rubra. The purification procedure involved saline extraction, (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and FPLC-gel filtration on Superdex peptide column. alpha- and beta-basrubrins exhibited a molecular weight of 4.3 and 5 kDa, respectively. They inhibited translation in a rabbit reticulocyte system with an IC(50) value of 400 and 100 nM, respectively. alpha- and beta-basrubrin inhibited HIV-1 reverse transcriptase by (79.4 +/- 7.8)% and (54.6 +/- 3.6)%, respectively, at a concentration of 400 microM, and (10.56 +/- 0.92)% and (2.12 +/- 0.81)%, respectively, at a concentration of 40 microM. Both alpha- and beta-basrubrins exerted potent antifungal activity toward Botrytis cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. PMID:11688973

  15. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. PMID:27297498

  16. Effects of peptide YY on gallbladder motility

    International Nuclear Information System (INIS)

    The effects of peptide YY (PYY) on cholecystokinin-stimulated gallbladder contraction were investigated in the prairie dog model. Twelve animals underwent laparotomy with catheter placement into the gallbladder and common bile duct (vent). The gallbladder was continuously perfused with [14C]polyethylene glycol-labeled lactated Ringer at 0.03 ml/min, and vent effluent was collected at 2.5-min intervals. All animals received 20 min of intravenous infusion of cholecystokinin octapeptide (CCK-OP), 2.5 ng x kg-1 x min-1, immediately followed by 60-min infusions of either lactated Ringer (LR) or synthetic PYY, 10 or 50 ng x kg-1 x min-1. When LR was infused after CCK-OP, gallbladder filling increased by 15.4 +/- 10.5% with minimal changes in gallbladder pressure. Infusion of PYY10 resulted in a significant increase in gallbladder volume and filling with a significant decrease in intragallbladder pressure. Similar findings were noted with PYY50. These data indicate that synthetic PYY significantly augments gallbladder filling after CCK-OP-stimulated gallbladder contraction. These finding, coupled with the observation that PYY inhibits pancreatic secretion, suggest that this peptide may be the anti-CCK hormone and may have an important role in regulating biliary activity postprandially

  17. Spider-Venom Peptides as Bioinsecticides

    Directory of Open Access Journals (Sweden)

    Glenn F. King

    2012-03-01

    Full Text Available Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world’s annual crop production and transmit many pathogens. Presently, arthropod pests of agricultural and health significance are controlled predominantly through the use of chemical insecticides. Unfortunately, the widespread use of these agrochemicals has resulted in genetic selection pressure that has led to the development of insecticide-resistant arthropods, as well as concerns over human health and the environment. Bioinsecticides represent a new generation of insecticides that utilise organisms or their derivatives (e.g., transgenic plants, recombinant baculoviruses, toxin-fusion proteins and peptidomimetics and show promise as environmentally-friendly alternatives to conventional agrochemicals. Spider-venom peptides are now being investigated as potential sources of bioinsecticides. With an estimated 100,000 species, spiders are one of the most successful arthropod predators. Their venom has proven to be a rich source of hyperstable insecticidal mini-proteins that cause insect paralysis or lethality through the modulation of ion channels, receptors and enzymes. Many newly characterized insecticidal spider toxins target novel sites in insects. Here we review the structure and pharmacology of these toxins and discuss the potential of this vast peptide library for the discovery of novel bioinsecticides.

  18. Enhancing Nonribosomal Peptide Biosynthesis in Filamentous Fungi

    Science.gov (United States)

    Soukup, Alexandra A.; Keller, Nancy P.; Wiemann, Philipp

    2016-01-01

    Filamentous fungi are historically known as rich sources for production of biologically active natural products, so-called secondary metabolites. One particularly pharmaceutically relevant chemical group of secondary metabolites is the nonribosomal peptides synthesized by nonribosomal peptide synthetases (NRPSs). As most of the fungal NRPS gene clusters leading to production of the desired molecules are not expressed under laboratory conditions, efforts to overcome this impediment are crucial to unlock the full chemical potential of each fungal species. One way to activate these silent clusters is by overexpressing and deleting global regulators of secondary metabolism. The conserved fungal-specific regulator of secondary metabolism, LaeA, was shown to be a valuable target for sleuthing of novel gene clusters and metabolites. Additionally, modulation of chromatin structures by either chemical or genetic manipulation has been shown to activate cryptic metabolites. Furthermore, NRPS-derived molecules seem to be affected by cross talk between the specific gene clusters and some of these metabolites have a tissue- or developmental-specific regulation. This chapter summarizes how this knowledge of different tiers of regulation can be combined to increase production of NRPS-derived metabolites in fungal species. PMID:26831707

  19. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth.

  20. DAMPD: A manually curated antimicrobial peptide database

    KAUST Repository

    Seshadri Sundararajan, Vijayaraghava

    2011-11-21

    The demand for antimicrobial peptides (AMPs) is rising because of the increased occurrence of pathogens that are tolerant or resistant to conventional antibiotics. Since naturally occurring AMPs could serve as templates for the development of new anti-infectious agents to which pathogens are not resistant, a resource that contains relevant information on AMP is of great interest. To that extent, we developed the Dragon Antimicrobial Peptide Database (DAMPD, http://apps.sanbi.ac.za/dampd) that contains 1232 manually curated AMPs. DAMPD is an update and a replacement of the ANTIMIC database. In DAMPD an integrated interface allows in a simple fashion querying based on taxonomy, species, AMP family, citation, keywords and a combination of search terms and fields (Advanced Search). A number of tools such as Blast, ClustalW, HMMER, Hydrocalculator, SignalP, AMP predictor, as well as a number of other resources that provide additional information about the results are also provided and integrated into DAMPD to augment biological analysis of AMPs. The Author(s) 2011. Published by Oxford University Press.

  1. Resistance to Antimicrobial Peptides in Vibrios

    Directory of Open Access Journals (Sweden)

    Delphine Destoumieux-Garzón

    2014-10-01

    Full Text Available Vibrios are associated with a broad diversity of hosts that produce antimicrobial peptides (AMPs as part of their defense against microbial infections. In particular, vibrios colonize epithelia, which function as protective barriers and express AMPs as a first line of chemical defense against pathogens. Recent studies have shown they can also colonize phagocytes, key components of the animal immune system. Phagocytes infiltrate infected tissues and use AMPs to kill the phagocytosed microorganisms intracellularly, or deliver their antimicrobial content extracellularly to circumvent tissue infection. We review here the mechanisms by which vibrios have evolved the capacity to evade or resist the potent antimicrobial defenses of the immune cells or tissues they colonize. Among their strategies to resist killing by AMPs, primarily vibrios use membrane remodeling mechanisms. In particular, some highly resistant strains substitute hexaacylated Lipid A with a diglycine residue to reduce their negative surface charge, thereby lowering their electrostatic interactions with cationic AMPs. As a response to envelope stress, which can be induced by membrane-active agents including AMPs, vibrios also release outer membrane vesicles to create a protective membranous shield that traps extracellular AMPs and prevents interaction of the peptides with their own membranes. Finally, once AMPs have breached the bacterial membrane barriers, vibrios use RND efflux pumps, similar to those of other species, to transport AMPs out of their cytoplasmic space.

  2. A novel peptide, selected from phage display library of random peptides, can efficiently target into human breast cancer cell

    Institute of Scientific and Technical Information of China (English)

    DONG Jian; LIU WeiQing; JIANG AiMei; ZHANG KeJian; CHEN MingQing

    2008-01-01

    To develop a targeting vector for breast cancer biotherapy, MDA-MB-231 cell, a human breast cancer cell line, was co-cultured with pC89 (9 aa) phage display library of random peptides. In multiple inde-pendent peptide-presenting phage screening trials, subtilisin was used as a protease to inactivate ex-tra-cellular phages. The internalized phages were collected by cell lysising and amplified in E. coli XLI-Blue. Through five rounds of selection, the peptide-presenting phages which could be internalized in MDA-MB-231 cells were isolated. A comparison was made between internalization capacities of pep-tide-presenting phages isolated from MDA-MB-231 cells and RGD-integrin binding phage by cocultur-ing them with other human tumor cell lines and normal cells. The nucleotide sequences of isolated peptide-presenting phages were then determined by DNA sequencing. To uncover whether phage coat protein or amino acid order was required for the character of the peptide to MDA-MB-231 cells, three peptides were synthesized. They are CASPSGALRSC, ASPSGALRS and CGVIFDHSVPC (the shifted sequence of CASPSGALRSC), and after coculturing them with different cell lines, their targeting ca-pacities to MDA-MB-231 cells were detected. These data suggested that the internalization process was highly selective, and capable of capturing a specific peptide from parent peptide variants. Moreover, the targeting internalization event of peptides was an amino acid sequence dependent manner. The results demonstrated the feasibility of using phage display library of random peptides to develop new targeting system for intracellular delivery of macromolecules, and the peptide we obtained might be modified as a targeting vector for breast cancer gene therapy.

  3. Improved Methods for the Enrichment and Analysis of Glycated Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Schepmoes, Athena A; Brock, Jonathan W; Wu, Si; Moore, Ronald J; Purvine, Samuel O; Baynes, John; Smith, Richard D; Metz, Thomas O

    2008-12-15

    Non-enzymatic glycation of tissue proteins has important implications in the development of complications of diabetes mellitus. Herein we report improved methods for the enrichment and analysis of glycated peptides using boronate affinity chromatography and electron transfer dissociation mass spectrometry, respectively. The enrichment of glycated peptides was improved by replacing an off-line desalting step with an on-line wash of column-bound glycated peptides using 50 mM ammonium acetate. The analysis of glycated peptides by MS/MS was improved by considering only higher charged (≥3) precursor-ions during data-dependent acquisition, which increased the number of glycated peptide identifications. Similarly, the use of supplemental collisional activation after electron transfer (ETcaD) resulted in more glycated peptide identifications when the MS survey scan was acquired with enhanced resolution. In general, acquiring ETD-MS/MS data at a normal MS survey scan rate, in conjunction with the rejection of both 1+ and 2+ precursor-ions, increased the number of identified glycated peptides relative to ETcaD or the enhanced MS survey scan rate. Finally, an evaluation of trypsin, Arg-C, and Lys-C showed that tryptic digestion of glycated proteins was comparable to digestion with Lys-C and that both were better than Arg-C in terms of the number glycated peptides identified by LC-MS/MS.

  4. Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

    NARCIS (Netherlands)

    de Sousa Pereira Simoes de Melo, Manuel; Ferre, Rafael; Feliu, Lidia; Bardaji, Eduard; Planas, Marta; Castanho, Miguel A. R. B.

    2011-01-01

    Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible co

  5. Responses of Transmembrane Peptide and Lipid Chains to Hydrophobic Mismatch

    Institute of Scientific and Technical Information of China (English)

    YANG Lei; LI Jian-tao; QI Hai-yan; LI Fei

    2012-01-01

    Hydrophobic mismatch between the hydrophobic length of membrane proteins and hydrophobic thickness of membranes is a crucial factor in controlling protein function and assembly.We combined fluorescence with circular dichroism(CD) and attenuated total reflection infrared(ATR-IR) spectroscopic methods to investigate the behaviors of the peptide and lipids under hydrophobic mismatch using a model peptide from the fourth transmembrane domain of natural resistance-associated macrophage protein 1 (Nramp 1),the phosphatidylcholines(PCs) and phosphatidylglycerols(PGs) with different lengths of acyl chains(14:0,16:0 and 18:0).In all PG lipid membranes,the peptide forms stable α-helix structure,and the helix axis is parallel to lipid chains.The helical span and orientation hardly change in varying thickness of PG membranes,while the lipid chains can deform to accommodate to the hydrophobic surface of embedded peptide.By comparison,the helical structures of the model peptide in PC lipid membranes are less stable.Upon incorporation with PC lipid membranes,the peptide can deform itself to accommodate to the hydrophobic thickness of lipid membranes in response to hydrophobic mismatch.In addition,hydrophobic mismatch can increase the aggregation propensity of the peptide in both PC and PG lipid membranes and the peptide in PC membranes has more aggregation tendency than that in PG membranes.

  6. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik;

    2014-01-01

    Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable pro...

  7. Cullin3-BTB interface: a novel target for stapled peptides.

    Directory of Open Access Journals (Sweden)

    Ivan de Paola

    Full Text Available Cullin3 (Cul3, a key factor of protein ubiquitination, is able to interact with dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad Complex domain. We here targeted the Cul3-BTB interface by using the intriguing approach of stabilizing the α-helical conformation of Cul3-based peptides through the "stapling" with a hydrocarbon cross-linker. In particular, by combining theoretical and experimental techniques, we designed and characterized stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49-68. Intriguingly, CD and NMR experiments demonstrate that these stapled peptides were able to adopt the helical structure that the fragment assumes in the parent protein. We also show that some of these peptides were able to bind to the BTB of the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with high affinity (~ 300-600 nM. Cul3-derived staple peptides are also able to bind the BTB of the pentameric KCTD5. Interestingly, the affinity of these peptides is of the same order of magnitude of that reported for the interaction of full-length Cul3 with some BTB containing proteins. Moreover, present data indicate that stapling endows these peptides with an increased serum stability. Altogether, these findings indicate that the designed stapled peptides can efficiently mimic protein-protein interactions and are potentially able to modulate fundamental biological processes involving Cul3.

  8. On-line multidimensional separation systems for peptide analysis

    NARCIS (Netherlands)

    Stroink, T.

    2005-01-01

    Today, there is an increasing interest in selective and sensitive analysis of proteins and peptides with a relatively high speed. The first chapter of this thesis describes several strategies for the on-line multidimensional analysis of peptides and proteins in biological samples. This overview of t

  9. The pharmacokinetics and pharmacodynamics of progastrin-derived peptides

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnaes

    2003-01-01

    The elimination of progastrin-derived peptides was a first-order process, also at supraphysiological concentrations in plasma. The site of extraction was dependent on the molecular size of the peptides and not on their bioactivity. Apart from the kidneys and brain, where the extraction was nonsel...

  10. Peptide-membrane Interactions by Spin-labeling EPR

    Science.gov (United States)

    Smirnova, Tatyana I.; Smirnov, Alex I.

    2016-01-01

    Site-directed spin labeling (SDSL) in combination with Electron Paramagnetic Resonance (EPR) spectroscopy is a well-established method that has recently grown in popularity as an experimental technique, with multiple applications in protein and peptide science. The growth is driven by development of labeling strategies, as well as by considerable technical advances in the field, that are paralleled by an increased availability of EPR instrumentation. While the method requires an introduction of a paramagnetic probe at a well-defined position in a peptide sequence, it has been shown to be minimally destructive to the peptide structure and energetics of the peptide-membrane interactions. In this chapter, we describe basic approaches for using SDSL EPR spectroscopy to study interactions between small peptides and biological membranes or membrane mimetic systems. We focus on experimental approaches to quantify peptide-membrane binding, topology of bound peptides, and characterize peptide aggregation. Sample preparation protocols including spin-labeling methods and preparation of membrane mimetic systems are also described. PMID:26477253

  11. Bioactive peptides released during of digestion of processed milk

    Science.gov (United States)

    Most of the proteins contained in milk consist of alpha-s1-, alpha-s2-, beta- and kappa-casein, and some of the peptides contained in these caseins may impart health benefits. To determine if processing affected release of peptides, samples of raw (R), homogenized (H), homogenized and pasteurized (...

  12. Origin and functional diversification of an amphibian defense peptide arsenal.

    Directory of Open Access Journals (Sweden)

    Kim Roelants

    Full Text Available The skin secretion of many amphibians contains an arsenal of bioactive molecules, including hormone-like peptides (HLPs acting as defense toxins against predators, and antimicrobial peptides (AMPs providing protection against infectious microorganisms. Several amphibian taxa seem to have independently acquired the genes to produce skin-secreted peptide arsenals, but it remains unknown how these originated from a non-defensive ancestral gene and evolved diverse defense functions against predators and pathogens. We conducted transcriptome, genome, peptidome and phylogenetic analyses to chart the full gene repertoire underlying the defense peptide arsenal of the frog Silurana tropicalis and reconstruct its evolutionary history. Our study uncovers a cluster of 13 transcriptionally active genes, together encoding up to 19 peptides, including diverse HLP homologues and AMPs. This gene cluster arose from a duplicated gastrointestinal hormone gene that attained a HLP-like defense function after major remodeling of its promoter region. Instead, new defense functions, including antimicrobial activity, arose by mutation of the precursor proteins, resulting in the proteolytic processing of secondary peptides alongside the original ones. Although gene duplication did not trigger functional innovation, it may have subsequently facilitated the convergent loss of the original function in multiple gene lineages (subfunctionalization, completing their transformation from HLP gene to AMP gene. The processing of multiple peptides from a single precursor entails a mechanism through which peptide-encoding genes may establish new functions without the need for gene duplication to avoid adaptive conflicts with older ones.

  13. C peptides as entry inhibitors for gene therapy.

    Science.gov (United States)

    Egerer, Lisa; Kiem, Hans-Peter; von Laer, Dorothee

    2015-01-01

    Peptides derived from the C-terminal heptad repeat 2 region of the HIV-1 gp41 envelope glycoprotein, so-called C peptides, are very potent HIV-1 fusion inhibitors. Antiviral genes encoding either membrane-anchored (ma) or secreted (iSAVE) C peptides have been engineered and allow direct in vivo production of the therapeutic peptides by genetically modified host cells. Membrane-anchored C peptides expressed in the HIV-1 target cells by T-cell or hematopoietic stem cell gene therapy efficiently prevent virus entry into the modified cells. Such gene-protection confers a selective survival advantage and allows accumulation of the genetically modified cells. Membrane-anchored C peptides have been successfully tested in a nonhuman primate model of AIDS and were found to be safe in a phase I clinical trial in AIDS patients transplanted with autologous gene-modified T-cells. Secreted C peptides have the crucial advantage of not only protecting genetically modified cells from HIV-1 infection, but also neighboring cells, thus suppressing virus replication even if only a small fraction of cells is genetically modified. Accordingly, various cell types can be considered as potential in vivo producer cells for iSAVE-based gene therapeutics, which could even be modified by direct in vivo gene delivery in future. In conclusion, C peptide gene therapeutics may provide a strong benefit to AIDS patients and could present an effective alternative to current antiretroviral drug regimens. PMID:25757622

  14. Bioinformatics Tools for the Discovery of New Nonribosomal Peptides

    DEFF Research Database (Denmark)

    Leclère, Valérie; Weber, Tilmann; Jacques, Philippe;

    2016-01-01

    and the deciphering of the domain architecture of the nonribosomal peptide synthetases (NRPSs). In the next step, candidate peptides synthesized by these NRPSs are predicted in silico, considering the specificity of incorporated monomers together with their isomery. To assess their novelty, the two...

  15. Semi-synthesis of nisin-based peptide antibiotics

    NARCIS (Netherlands)

    Slootweg, J.C.

    2013-01-01

    There is a growing need for novel antibiotics since there are more and more cases of infections caused by resistant bacteria. Possible novel antibiotics are antimicrobial peptides, especially the lantibiotic nisin. Lantibiotics are ribosomally synthesized cationic peptides that contain several unnat

  16. Method for synthesizing peptides with saccharide linked enzyme polymer conjugates

    Science.gov (United States)

    Callstrom, M.R.; Bednarski, M.D.; Gruber, P.R.

    1997-06-17

    A method is disclosed for synthesizing peptides using water soluble enzyme polymer conjugates. The method comprises catalyzing the peptide synthesis with enzyme which has been covalently bonded to a polymer through at least three linkers which linkers have three or more hydroxyl groups. The enzyme is conjugated at lysines or arginines. 19 figs.

  17. Interpretation of tandem mass spectra of posttranslationally modified peptides

    DEFF Research Database (Denmark)

    Bunkenborg, J.; Matthiesen, R.

    2013-01-01

    Tandem mass spectrometry provides a sensitive means of analyzing the amino acid sequence of peptides and modified peptides by providing accurate mass measurements of precursor and fragment ions. Modern mass spectrometry instrumentation is capable of rapidly generating many thousands of tandem mas...

  18. A highly scalable peptide-based assay system for proteomics.

    Directory of Open Access Journals (Sweden)

    Igor A Kozlov

    Full Text Available We report a scalable and cost-effective technology for generating and screening high-complexity customizable peptide sets. The peptides are made as peptide-cDNA fusions by in vitro transcription/translation from pools of DNA templates generated by microarray-based synthesis. This approach enables large custom sets of peptides to be designed in silico, manufactured cost-effectively in parallel, and assayed efficiently in a multiplexed fashion. The utility of our peptide-cDNA fusion pools was demonstrated in two activity-based assays designed to discover protease and kinase substrates. In the protease assay, cleaved peptide substrates were separated from uncleaved and identified by digital sequencing of their cognate cDNAs. We screened the 3,011 amino acid HCV proteome for susceptibility to cleavage by the HCV NS3/4A protease and identified all 3 known trans cleavage sites with high specificity. In the kinase assay, peptide substrates phosphorylated by tyrosine kinases were captured and identified by sequencing of their cDNAs. We screened a pool of 3,243 peptides against Abl kinase and showed that phosphorylation events detected were specific and consistent with the known substrate preferences of Abl kinase. Our approach is scalable and adaptable to other protein-based assays.

  19. Information-driven modeling of protein-peptide complexes.

    Science.gov (United States)

    Trellet, Mikael; Melquiond, Adrien S J; Bonvin, Alexandre M J J

    2015-01-01

    Despite their biological importance in many regulatory processes, protein-peptide recognition mechanisms are difficult to study experimentally at the structural level because of the inherent flexibility of peptides and the often transient interactions on which they rely. Complementary methods like biomolecular docking are therefore required. The prediction of the three-dimensional structure of protein-peptide complexes raises unique challenges for computational algorithms, as exemplified by the recent introduction of protein-peptide targets in the blind international experiment CAPRI (Critical Assessment of PRedicted Interactions). Conventional protein-protein docking approaches are often struggling with the high flexibility of peptides whose short sizes impede protocols and scoring functions developed for larger interfaces. On the other side, protein-small ligand docking methods are unable to cope with the larger number of degrees of freedom in peptides compared to small molecules and the typically reduced available information to define the binding site. In this chapter, we describe a protocol to model protein-peptide complexes using the HADDOCK web server, working through a test case to illustrate every steps. The flexibility challenge that peptides represent is dealt with by combining elements of conformational selection and induced fit molecular recognition theories. PMID:25555727

  20. History and diagnostic significance of C-peptide.

    Science.gov (United States)

    Brandenburg, Dietrich

    2008-01-01

    Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rapidly growing number of clinical investigations. A prerequisite was the development of specific immuno assays for proinsulin and C-peptide. Further milestones were: the chemical synthesis of several C-peptides and the accomplishments in the synthesis of proinsulin; the detection of preproinsulin with its bearings on understanding protein biosynthesis; the pioneering role of insulin, proinsulin, C-peptide, and mini-C-peptides in the development of recombinant DNA technology; and the discovery of the enzymes for the endoproteolytic processing of proinsulin into insulin and C-peptide, completing the pathway of biosynthesis. Today, C-peptide continues to serve as a special diagnostic tool in Diabetology and related fields. Thus, its passive role is well established. Evidence for its active role in physiology and pathophysiology is more recent and is subject of the following contributions. PMID:18509495

  1. C-Peptide Effects on Renal Physiology and Diabetes

    Directory of Open Access Journals (Sweden)

    L. Rebsomen

    2008-01-01

    Full Text Available The C-peptide of proinsulin is important for the biosynthesis of insulin and has for a long time been considered to be biologically inert. Animal studies have shown that some of the renal effects of the C-peptide may in part be explained by its ability to stimulate the Na,K-ATPase activity. Precisely, the C-peptide reduces diabetes-induced glomerular hyperfiltration both in animals and humans, therefore, resulting in regression of fibrosis. The tubular function is also concerned as diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with the reduction of the diabetes-induced glomerular hyperfiltration. The tubular effectors of C-peptide were considered to be tubule transporters, but recent studies have shown that biochemical pathways involving cellular kinases and inflammatory pathways may also be important. The matter theory concerning the C-peptide effects is a metabolic one involving the effects of the C-peptide on lipidic metabolic status.This review concentrates on the most convincing data which indicate that the C-peptide is a biologically active hormone for renal physiology.

  2. Studies on human proinsulin.C-peptide radioimmunoassay method

    International Nuclear Information System (INIS)

    125I-labelled human.C-peptide was prepared by the chloramin T method, the enzymic method and the active ester method, respectively. Using respective 125I-labelled human.C-peptides in human proinsulin.C-peptide RIA, we compared the binding (B0/T %) to antibody, displacement by standard human.C-peptide, recovery, and stability. The usable 125I-labelled antigen for human proinsulin.C-peptide RIA could be prepared by the chloramin T method and the enzymic method which labelled 125I to tyrosyl human proinsulin connecting peptide, and by an active ester method which conjugates 125I-labelled active ester to human proinsulin connecting peptide. No differences among those 125I-labelled antigens were observed in displacement (B/B0 %) by standard human.C-peptide or the recovery test. In the case of constant preparation of 125I-labelled antigen for RIA, the enzymic method was the best from the viewpoint that reaction ratio is stable and the stability of B0/T % was good. (auth.)

  3. Bicyclic peptide inhibitor of urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Roodbeen, Renée; Jensen, Berit Paaske; Jiang, Longguang;

    2013-01-01

    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptide-based inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...

  4. Neuromedin and FN-38 Peptides for Treating Psychiatric Diseases

    Science.gov (United States)

    Methods and compositions for treating psychiatric diseases and disorders are disclosed. The methods provided generally involve the administration of an NMX peptide, an FNX peptide, or an NMX receptor agonist, or analogs or derivatives thereof, to a subject in order to treat psychiatric diseases and ...

  5. Peptide-Mediated Blood-Brain Barrier Transport of Polymersomes

    NARCIS (Netherlands)

    Georgieva, J.V.; Brinkhuis, R.P.; Stojanov, K.; Weijers, C.A.G.M.; Zuilhof, H.; Rutjes, F.P.J.T.; Hoekstra, D.; Hest, van J.C.M.; Zuhorn, I.S.

    2012-01-01

    A polymeric nanocarrier: Polymersomes tagged with a dodecamer peptide that recognizes gangliosides GM1 and GT1b are shown to cross the blood–brain barrier, both in an in vitro model and in vivo (see picture). The combination of polymeric vesicles with a small GM1-binding peptide and GM1/GT1b ganglio

  6. Carrier peptide-mediated transepithelial permeation of biopharmaceuticals

    DEFF Research Database (Denmark)

    Kristensen, Mie; Nielsen, Hanne Mørck

    2015-01-01

    -penetrating peptides (CPPs). Two approaches for the carrier peptide-mediated transepithelial permeation of biopharmaceuticals are generally explored: Co-administration1 or covalent conjugation2. Co-administration is often the method of choice due to e.g. ease in sample preparation and flexibility in adjustment...

  7. Peptide synthesis in neat organic solvents with novel thermostable proteases

    NARCIS (Netherlands)

    Toplak, Ana; Nuijens, Timo; Quaedflieg, Peter J L M; Wu, Bian; Janssen, Dick B

    2015-01-01

    Biocatalytic peptide synthesis will benefit from enzymes that are active at low water levels in organic solvent compositions that allow good substrate and product solubility. To explore the use of proteases from thermophiles for peptide synthesis under such conditions, putative protease genes of the

  8. Synthetic Peptides as Receptors in Affinity Sensors: A Feasibility Study

    NARCIS (Netherlands)

    Heuvel, van den Dave J.; Kooyman, Rob P.H.; Drijfhout, Jan Wouter; Welling, Gjalt W.

    1993-01-01

    A relatively simple method for immobilizing synthetic peptides as a receptor onto a gold surface using the self-assembling monolayer (SAM) technique has been investigated. A synthetic peptide with an amino acid sequence similar to the 9-21 gD sequence of herpes simplex virus type 1 was modified with

  9. Chemo-enzymatic peptide synthesis : bioprocess engineering aspects

    NARCIS (Netherlands)

    Vossenberg, P.

    2012-01-01

      Peptides, in particular oligopeptides, play an important role in the fields of health care, nutrition and cosmetics. Chemical synthesis is currently the most mature technique for the synthesis of peptides that range in length from 5 to 80 amino acids. Chemical synthesis is, however, expected

  10. Peptide Nucleic Acids Having Enhanced Binding Affinity and Sequence Specificity

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. Methods of increasing binding affinity and sequence specificity of peptide nucleic aci...

  11. Peptide Nucleic Acids Having Amino Acid Side Chains

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of nat...

  12. Peptide Nucleic Acids Having 2,6-Diaminopurine Nucleobases

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group cons...

  13. Chemical instability of pharmaceutical peptides in polymeric controlled release systems

    NARCIS (Netherlands)

    Shirangi, M.

    2015-01-01

    Peptide and protein drugs are presently an important class of pharmaceuticals due to their favorable properties, i.e. high and selective activity. However, peptides and proteins are relatively sensitive for degradation and therefore there is need for investigation of the chemical stability of these

  14. Cell-penetrating antimicrobial peptides - prospectives for targeting intracellular infections

    DEFF Research Database (Denmark)

    Bahnsen, Jesper S; Franzyk, Henrik; Sayers, Edward J;

    2015-01-01

    La WT cells and analyzed by flow cytometry and confocal microscopy. Furthermore, the effects of the peptides on eukaryotic cell viability as well as their antimicrobial effect were tested. In addition, the disrupting ability of the peptides in the presence of bilayer membranes of different composition...

  15. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

    OpenAIRE

    Yin, HaiFang; Boisguerin, Prisca; Moulton, Hong M.; Betts, Corinne; Seow, Yiqi; Boutilier, Jordan; Wang, Qingsong; Walsh, Anthony; Lebleu, Bernard; Wood, Matthew JA

    2013-01-01

    We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was ...

  16. Keratin-based peptide : biological evaluation and strengthening properties on relaxed hair

    OpenAIRE

    Fernandes, Margarida M.; Lima, Cristóvão F; Loureiro, Ana; Gomes, A. C.; Paulo, Artur Cavaco

    2012-01-01

    A peptide based on a fragment of hair keratin type II cuticular protein, keratin peptide (KP), was studied as a possible strengthening agent for weakened relaxed hair. The peptide was prepared both in aqueous water formulation (WF) and organic solvent formulations (OF), to determine the effect of organic solvents on peptide interaction with hair and the differences in hair recovery. Both peptide formulations were shown to improve mechanical and thermal properties of weakened hair with peptide...

  17. Optimization for Peptide Sample Preparation for Urine Peptidomics

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; Nicora, Carrie D.; Hsieh, Szu-Chuan; Dai, Hong; Qian, Weijun; Camp, David G.; Sarwal, Minnie M.

    2014-02-25

    Analysis of native or endogenous peptides in biofluids can provide valuable insights into disease mechanisms. Furthermore, the detected peptides may also have utility as potential biomarkers for non-invasive monitoring of human diseases. The non-invasive nature of urine collection and the abundance of peptides in the urine makes analysis by high-throughput ‘peptidomics’ methods , an attractive approach for investigating the pathogenesis of renal disease. However, urine peptidomics methodologies can be problematic with regards to difficulties associated with sample preparation. The urine matrix can provide significant background interference in making the analytical measurements that it hampers both the identification of peptides and the depth of the peptidomics read when utilizing LC-MS based peptidome analysis. We report on a novel adaptation of the standard solid phase extraction (SPE) method to a modified SPE (mSPE) approach for improved peptide yield and analysis sensitivity with LC-MS based peptidomics in terms of time, cost, clogging of the LC-MS column, peptide yield, peptide quality, and number of peptides identified by each method. Expense and time requirements were comparable for both SPE and mSPE, but more interfering contaminants from the urine matrix were evident in the SPE preparations (e.g., clogging of the LC-MS columns, yellowish background coloration of prepared samples due to retained urobilin, lower peptide yields) when compared to the mSPE method. When we compared data from technical replicates of 4 runs, the mSPE method provided significantly improved efficiencies for the preparation of samples from urine (e.g., mSPE peptide identification 82% versus 18% with SPE; p = 8.92E-05). Additionally, peptide identifications, when applying the mSPE method, highlighted the biology of differential activation of urine peptidases during acute renal transplant rejection with distinct laddering of specific peptides, which was obscured for most proteins

  18. A novel affinity purification method to isolate peptide specific antibodies

    DEFF Research Database (Denmark)

    Karlsen, Alan E; Lernmark, A; Kofod, Hans;

    1990-01-01

    with the beads and after a wash step the bound antibodies were eluted in 1 M acetic acid. The eluted material was composed predominantly of intact immunoglobulin as evidenced by the presence of heavy and light chain bands in SDS-PAGE. The eluted antibodies were peptide specific in ELISA and bound only to intact......Site-specific, high affinity polyclonal antisera are effectively and successfully produced by immunizing rabbits with synthetic peptides. The use of these antisera in subsequent immune analysis is often limited because of non-specific binding. We describe a new and simple method to effectively...... affinity-purify anti-peptide antibodies. To test our system, rabbits were immunized with model peptides representing sequences of the putative rabbit growth hormone receptor and several HLA-DQ beta-chain molecules. Polystyrene plastic beads were coated with peptides. Immune serum was incubated...

  19. SuperMimic – Fitting peptide mimetics into protein structures

    Directory of Open Access Journals (Sweden)

    Schmidt Ulrike

    2006-01-01

    Full Text Available Abstract Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently.

  20. Inhibiting the inhibitors: retro-inverso Smac peptides.

    Science.gov (United States)

    Hossbach, Julia; Michalsky, Elke; Henklein, Peter; Jaeger, Marten; Daniel, Peter T; Preissner, Robert

    2009-12-01

    Resistance against apoptosis-inducing anti-cancer drugs remains a severe problem in therapy. One reason is the overexpression of inhibitors of apoptosis proteins (IAPs), a group of proteins responsible for the prevention of apoptosis induction by inactivation of initiator caspases. The natural inhibitor of the IAPs is the protein Smac, which impedes the binding to the caspases. Although Smac is a potent inhibitor, Smac peptides are not very stable in vivo and thus not applicable in therapy. Bioinformatical methods were applied to design Smac-derived peptides to break the therapy resistance in IAP high-expressing tumor cells. The exchange of amino acids in the Smac peptides AVPI and AVPF against unnatural amino acids leads to an improvement of the apoptosis sensitivity. The variety of Smac peptides was filtered by computational docking. Moreover, Smac-derived peptides with sufficient binding to the IAPs were tested in IAP-expressing Hodgkin Lymphoma cell lines.

  1. SuperMimic – Fitting peptide mimetics into protein structures

    Science.gov (United States)

    Goede, Andrean; Michalsky, Elke; Schmidt, Ulrike; Preissner, Robert

    2006-01-01

    Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently. PMID:16403211

  2. Self-assembled peptide nanostructures for functional materials

    Science.gov (United States)

    Sardan Ekiz, Melis; Cinar, Goksu; Aref Khalily, Mohammad; Guler, Mustafa O.

    2016-10-01

    Nature is an important inspirational source for scientists, and presents complex and elegant examples of adaptive and intelligent systems created by self-assembly. Significant effort has been devoted to understanding these sophisticated systems. The self-assembly process enables us to create supramolecular nanostructures with high order and complexity, and peptide-based self-assembling building blocks can serve as suitable platforms to construct nanostructures showing diverse features and applications. In this review, peptide-based supramolecular assemblies will be discussed in terms of their synthesis, design, characterization and application. Peptide nanostructures are categorized based on their chemical and physical properties and will be examined by rationalizing the influence of peptide design on the resulting morphology and the methods employed to characterize these high order complex systems. Moreover, the application of self-assembled peptide nanomaterials as functional materials in information technologies and environmental sciences will be reviewed by providing examples from recently published high-impact studies.

  3. Photodissociation pathways and lifetimes of protonated peptides and their dimers

    DEFF Research Database (Denmark)

    Gopalan, Aravind; Klærke, Benedikte; Rajput, Jyoti;

    2012-01-01

    Photodissociation lifetimes and fragment channels of gas-phase, protonated YAn (n = 1,2) peptides and their dimers were measured with 266 nm photons. The protonated monomers were found to have a fast dissociation channel with an exponential lifetime of ∼200 ns while the protonated dimers show an...... channel in the dimer was found to result in cleavage of the H-bonds after energy transfer through these H-bonds. In general, the dissociation of these protonated peptides is non-prompt and the decay time was found to increase with the size of the peptides. Quantum RRKM calculations of the microcanonical...... equipartition theorem. It demonstrates encouraging results in predicting fragmentation lifetimes of protonated peptides. Finally, we present the first experimental evidence for a photo-induced conversion of tyrosine-containing peptides into monocyclic aromatic hydrocarbon along with a formamide molecule both...

  4. Peptide synthesis on glass substrate using acoustic droplet ejector.

    Science.gov (United States)

    Youngki Choe; Shih-Jui Chen; Eun Sok Kim

    2014-03-01

    This paper describes the synthesis of a 9-mers-long peptide ladder structure of glycine on a modified glass surface using a nanoliter droplet ejector. To synthesize peptide on a glass substrate, SPOT peptide synthesis protocol was followed with a nozzleless acoustic droplet ejector being used to eject about 300 droplets of preactivated amino acid solution to dispense 60 nL of the solution per mer. The coupling efficiency of each mer was measured with FITC fluorescent tag to be 96%, resulting in net 70% efficiency for the whole 9-mer-long peptide of glycine. Usage of a nanoliter droplet ejector for SPOT peptide synthesis increases the density of protein array on a chip. PMID:24235271

  5. The role of antimicrobial peptides in cardiovascular physiology and disease.

    Science.gov (United States)

    Li, Yifeng

    2009-12-18

    Antimicrobial peptides are natural peptide antibiotics, existing ubiquitously in both plant and animal kingdoms. They exhibit broad-spectrum antimicrobial activity and play an important role in host defense against invading microbes. Recently, these peptides have been shown to possess activities unrelated to direct microbial killing and be involved in the complex network of immune responses and inflammation. Thus, their role has now broadened beyond that of endogenous antibiotics. Because of their wide involvement in inflammatory response and the emerging role of inflammation in atherosclerosis, antimicrobial peptides have been proposed to represent an important link between inflammation and the pathogenesis of atherosclerotic cardiovascular diseases. This review highlights recent findings that support a role of these peptides in cardiovascular physiology and disease.

  6. Peptide synthesis in neat organic solvents with novel thermostable proteases.

    Science.gov (United States)

    Toplak, Ana; Nuijens, Timo; Quaedflieg, Peter J L M; Wu, Bian; Janssen, Dick B

    2015-06-01

    Biocatalytic peptide synthesis will benefit from enzymes that are active at low water levels in organic solvent compositions that allow good substrate and product solubility. To explore the use of proteases from thermophiles for peptide synthesis under such conditions, putative protease genes of the subtilase class were cloned from Thermus aquaticus and Deinococcus geothermalis and expressed in Escherichia coli. The purified enzymes were highly thermostable and catalyzed efficient peptide bond synthesis at 80°C and 60°C in neat acetonitrile with excellent conversion (>90%). The enzymes tolerated high levels of N,N-dimethylformamide (DMF) as a cosolvent (40-50% v/v), which improved substrate solubility and gave good conversion in 5+3 peptide condensation reactions. The results suggest that proteases from thermophiles can be used for peptide synthesis under harsh reaction conditions.

  7. Interaction of peptides with cell membranes: insights from molecular modeling

    International Nuclear Information System (INIS)

    The investigation of the interaction of peptides with cell membranes is the focus of active research. It can enhance the understanding of basic membrane functions such as membrane transport, fusion, and signaling processes, and it may shed light on potential applications of peptides in biomedicine. In this review, we will present current advances in computational studies on the interaction of different types of peptides with the cell membrane. Depending on the properties of the peptide, membrane, and external environment, the peptide–membrane interaction shows a variety of different forms. Here, on the basis of recent computational progress, we will discuss how different peptides could initiate membrane pores, translocate across the membrane, induce membrane endocytosis, produce membrane curvature, form fibrils on the membrane surface, as well as interact with functional membrane proteins. Finally, we will present a conclusion summarizing recent progress and providing some specific insights into future developments in this field. (topical review)

  8. Membrane-spanning peptides and the origin of life.

    Science.gov (United States)

    Bywater, Robert P

    2009-12-01

    An explanation is given as to why membrane-spanning peptides must have been the first "information-rich" molecules in the development of life. These peptides are stabilised in a lipid bilayer membrane environment and they are preferentially made from the simplest, and likewise oldest, of the amino acids that survive today. Transmembrane peptides can exercise functions that are essential for biological systems such as signal transduction and material transport across membranes. More complex peptides possessing catalytic properties could later develop on either side of the membrane as independently folding functional units formed by extension of the protruding ends of the transmembrane peptides within an aqueous environment and thereby give rise to more of the functions that are necessary for life. But the membrane was the cradle for the development of the first information-rich biomolecules. PMID:19679140

  9. Peptide folding in the presence of interacting protein crowders

    Science.gov (United States)

    Bille, Anna; Mohanty, Sandipan; Irbäck, Anders

    2016-05-01

    Using Monte Carlo methods, we explore and compare the effects of two protein crowders, BPTI and GB1, on the folding thermodynamics of two peptides, the compact helical trp-cage and the β-hairpin-forming GB1m3. The thermally highly stable crowder proteins are modeled using a fixed backbone and rotatable side-chains, whereas the peptides are free to fold and unfold. In the simulations, the crowder proteins tend to distort the trp-cage fold, while having a stabilizing effect on GB1m3. The extent of the effects on a given peptide depends on the crowder type. Due to a sticky patch on its surface, BPTI causes larger changes than GB1 in the melting properties of the peptides. The observed effects on the peptides stem largely from attractive and specific interactions with the crowder surfaces, and differ from those seen in reference simulations with purely steric crowder particles.

  10. Peptide linkers for the assembly of semiconductor quantum dot bioconjugates

    Science.gov (United States)

    Boeneman, Kelly; Mei, Bing C.; Deschamps, Jeffrey R.; Delehanty, James B.; Mattoussi, Hedi; Medintz, Igor

    2009-02-01

    The use of semiconductor luminescent quantum dots for the labeling of biomolecules is rapidly expanding, however it still requires facile methods to attach functional globular proteins to biologically optimized quantum dots. Here we discuss the development of controlled variable length peptidyl linkers to attach biomolecules to poly(ethylene) glycol (PEG) coated quantum dots for both in vitro and in vivo applications. The peptides chosen, β-sheets and alpha helices are appended to polyhistidine sequences and this allows for control of the ratio of peptide bioconjugated to QD and the distance from QD to the biomolecule. Recombinant DNA engineering, bacterial peptide expression and Ni-NTA purification of histidine labeled peptides are utilized to create the linkers. Peptide length is confirmed by in vitro fluorescent resonance energy transfer (FRET).

  11. Peptides and aging: Their role in anorexia and memory.

    Science.gov (United States)

    Morley, John E

    2015-10-01

    The rapid aging of the world's population has led to a need to increase our understanding of the pathophysiology of the factors leading to frailty and cognitive decline. Peptides have been shown to be involved in the pathophysiology of frailty and cognitive decline. Weight loss is a major component of frailty. In this review, we demonstrate a central role for both peripheral peptides (e.g., cholecystokinin and ghrelin) and neuropeptides (e.g., dynorphin and alpha-MSH) in the pathophysiology of the anorexia of aging. Similarly, peripheral peptides (e.g., ghrelin, glucagon-like peptide 1, and cholecystokinin) are modulators of memory. A number of centrally acting neuropeptides have also been shown to modulate cognitive processes. Amyloid-beta peptide in physiological levels is a memory enhancer, while in high (pathological) levels, it plays a key role in the development of Alzheimer's disease.

  12. Antimicrobial activity of mosquito cecropin peptides against Francisella.

    Science.gov (United States)

    Kaushal, Akanksha; Gupta, Kajal; Shah, Ruhee; van Hoek, Monique L

    2016-10-01

    Francisella tularensis is the cause of the zoonotic disease tularemia. In Sweden and Scandinavia, epidemiological studies have implicated mosquitoes as a vector. Prior research has demonstrated the presence of Francisella DNA in infected mosquitoes but has not shown definitive transmission of tularemia from a mosquito to a mammalian host. We hypothesized that antimicrobial peptides, an important component of the innate immune system of higher organisms, may play a role in mosquito host-defense to Francisella. We established that Francisella sp. are susceptible to two cecropin antimicrobial peptides derived from the mosquito Aedes albopictus as well as Culex pipiens. We also demonstrated induced expression of Aedes albopictus antimicrobial peptide genes by Francisella infection C6/36 mosquito cell line. We demonstrate that mosquito antimicrobial peptides act against Francisella by disrupting the cellular membrane of the bacteria. Thus, it is possible that antimicrobial peptides may play a role in the inability of mosquitoes to establish an effective natural transmission of tularemia. PMID:27235883

  13. Epithelial antimicrobial peptides in host defense against infection

    Directory of Open Access Journals (Sweden)

    Bals Robert

    2000-10-01

    Full Text Available Abstract One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. In the airways, α-defensins and the cathelicidin LL-37/hCAP-18 originate from neutrophils. β-Defensins and LL-37/hCAP-18 are produced by the respiratory epithelium and the alveolar macrophage and secreted into the airway surface fluid. Beside their direct antimicrobial function, antimicrobial peptides have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing such diverse processes as proliferation, immune induction, wound healing, cytokine release, chemotaxis, protease-antiprotease balance, and redox homeostasis. Further, antimicrobial peptides qualify as prototypes of innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation.

  14. Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

    Directory of Open Access Journals (Sweden)

    Anna-Sophia Wisser

    2010-01-01

    Full Text Available Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK, bombesin, desacyl ghrelin, peptide YY (PYY, as well as glucagon-like peptide (GLP. Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite.

  15. Cathelicidin peptides as candidates for a novel class of antimicrobials.

    Science.gov (United States)

    Zanetti, Margherita; Gennaro, Renato; Skerlavaj, Barbara; Tomasinsig, Linda; Circo, Raffaella

    2002-01-01

    Cathelicidin peptides are a numerous group of mammalian cationic antimicrobial peptides. Despite a common evolutionary origin of their genes, peptides display a remarkable variety of sizes, sequences and structures. Their spectra of antimicrobial activity are varied and cover a range of organisms that includes bacteria, fungi and enveloped viruses. In addition, they bind to and neutralize the effects of endotoxin. These features make this family of peptides good candidates in view of a therapeutic use. The most promising ones are currently under evaluation as leads for the development of novel anti-infectives, and synthetic variants are in an advanced stage of development for specific clinical applications. This review focuses on recent studies on the structure and in vitro and in vivo biological activities of these peptides. PMID:11945171

  16. Describing the Peptide Binding Specificity of HLA-C

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Harndahl, Mikkel Nors; Nielsen, Morten;

    for 5 HLA-C molecules and for all, but one, molecule we find a high frequency of binders, >70%, among these peptides. To extend the examined peptide space, we use bioinformatic prediction tools to search for additional binders. Finally, we update our prediction tool, NetMHCpan, with the HLA-C affinity......Human leukocyte antigen (HLA) presents peptides to T-cells for immune scrutiny. Whereas HLA-A and -B have been described in great detail, HLA-C has received much less attention. Here, to increase the coverage of HLA-C and the accuracy of the corresponding tools, we have generated HLA-C molecules......; peptide-binding assays, data and predictors; and tetramers; representing the most prevalent HLA-C molecules. We have combined positional scanning combinatorial peptide library (PSCPL) with a homogenous high-throughput dissociation assay and generated specificity matrices for 11 different HLA-C molecules...

  17. Stability of peptides in high-temperature aqueous solutions

    Science.gov (United States)

    Shock, Everett L.

    1992-09-01

    Estimated standard molal thermodynamic properties of aqueous dipeptides and their constituent amino acids indicate that temperature increases correspond to increased stability of peptide bonds relative to hydrolysis reactions. Pressure increases cause slight decreases in peptide bond stability, which are generally offset by greater stability caused by temperature increases along geothermal gradients. These calculations suggest that peptides, polypeptides, and proteins may survive hydrothermal alteration of organic matter depending on the rates of the hydrolysis reactions. Extremely thermophilic organisms may be able to take advantage of the decreased energy required to form peptide bonds in order to maintain structural proteins and enzymes at elevated temperatures and pressures. As the rates of hydrolysis reactions increase with increasing temperature, formation of peptide bonds may become a facile process in hydrothermal systems and deep in sedimentary basins.

  18. Antimicrobial peptides: natural templates for synthetic membrane-active compounds.

    Science.gov (United States)

    Giuliani, A; Pirri, G; Bozzi, A; Di Giulio, A; Aschi, M; Rinaldi, A C

    2008-08-01

    The innate immunity of multicellular organisms relies in large part on the action of antimicrobial peptides (AMPs) to resist microbial invasion. Crafted by evolution into an extremely diversified array of sequences and folds, AMPs do share a common amphiphilic 3-D arrangement. This feature is directly linked with a common mechanism of action that predominantly (although not exclusively) develops upon interaction of peptides with cell membranes of target cells. This minireview reports on current understanding of the modes of interaction of AMPs with biological and model membranes, especially focusing on recent insights into the folding and oligomerization requirements of peptides to bind and insert into lipid membranes and exert their antibiotic effects. Given the potential of AMPs to be developed into a new class of anti-infective agents, emphasis is placed on how the information on peptide-membrane interactions could direct the design and selection of improved biomimetic synthetic peptides with antibiotic properties.

  19. C-type natriuretic-derived peptides as biomarkers in human disease

    DEFF Research Database (Denmark)

    Lippert, Solvej Kølvraa; Goetze, Jens Peter

    2010-01-01

    The natriuretic peptide system comprises three structurally related peptides: atrial natriuretic peptide, B-type natriuretic peptide and C-type natriuretic peptide. In circulation, they play an important endocrine role in the regulation of cardiovascular homeostasis by maintaining blood pressure...... and extracellular fluid volume. Atrial natriuretic peptide and B-type natriuretic peptide have gained considerable diagnostic interest as biomarkers in cardiovascular disease. By contrast, C-type natriuretic peptide has not yet been ascribed a role in human diagnostics. This perspective aims at recapitulating...

  20. Characterization of foot-and-mouth disease virus's viral peptides with LC-ESI-MS

    International Nuclear Information System (INIS)

    Peptides and proteins play a central role in numerous biological and physiological processes in living organisms. Viral capsid peptides are part of the viruses' outer shell of genetic materials. Viruses are recognized by immune system via capsid peptides. Depending on this property of capsid peptides, prototypes synthetic peptide-based vaccine can be developed. In this work, we synthesized three different viral peptide sequences of foot-and-mouth disease virus with microwave enhanced solid phase synthesis method. These peptides were characterized by using liquid chromatography electro spray interface mass spectrometry (LC-ESI-MS) with electro spray ionization. We briefly describe the essential facts for peptide characterization. (author)

  1. Amyloid Beta-peptide (25-35) changes (Ca2+) in hippocampal neurons

    DEFF Research Database (Denmark)

    Mogensen, Helle Smidt; Beatty, Diane; Morris, Stephen;

    1998-01-01

    neuroscience, Alzheimer, calcium ion, hippocampal neurons, amyloid-beta-peptide, hydrogen ion, rat......neuroscience, Alzheimer, calcium ion, hippocampal neurons, amyloid-beta-peptide, hydrogen ion, rat...

  2. TUMOR SELECTIVE DRUG DELIVERY BY NEUROTENSIN BRANCHED PEPTIDES

    Directory of Open Access Journals (Sweden)

    L. Depau

    2012-05-01

    Full Text Available Detection of new tumor-selective targets, which allow either cancer cell tracing or therapy, is a crucial issue in cancer research. Membrane receptors for endogenous peptides such as Neurotensin are over-expressed in many human cancers and could therefore be used as tumor-specific antigen, while peptide ligands might act as targeting agents. The development of peptides as drug has always been limited by their short half-life, due to degradation by peptidases and proteases. Chemical modification, which can stabilize the molecules, may modify peptide affinity or specificity. More- over, coupling of peptides to effector units for imaging or therapy, may interfere with biological activity. We demonstrated that peptide sequences, when synthesized in an oligo-branched form, be- come resistant to proteolysis and thank to their multimericity are more efficient than correspon- ding monomers in binding cellular antigens1. Moreover, the branched core allow coupling of effector units without affecting peptide activity. Drug-armed tetra-branched neurotensin peptides (NT4 were synthesized with different conjugation methods, resulting either in uncleavable adducts or drug-releasing molecules2-4. Recently we de- veloped DOPC liposomes filled with the cytotoxic drug Doxorubicin (Doxo and functionalized with NT4. Armed DOPC liposomes showed a clear advantage with respect to nude liposomes in drug internalization and their cytotoxicity is fourfold increased with respect to the same nude lipo- somes. Conjugation to NT4 switches drug internalization to a peptide-receptor mediated mechanism, which greatly increases drug selectivity and also might allow by-passing drug cell resistance. In vitro and in vivo results indicated that branched NT peptides are valuable tools for tumor selective targeting.

  3. Review: Production and functionality of active peptides from milk.

    Science.gov (United States)

    Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A

    2011-08-01

    In recent years, research on the production of active peptides obtained from milk and their potential functionality has grown, to a great extent. Bioactive peptides have been defined as specific protein fragments that have a positive impact on body functions or conditions, and they may ultimately have an influence on health. Individual proteins of casein or milk-derived products such as cheese and yogurt have been used as a protein source to study the isolation and activity of peptides with several applications. Currently, the milk whey waste obtained in the production of cheese also represents a protein source from which active peptides could be isolated with potential industrial applications. The active properties of milk peptides and the results found with regard to their physiological effects have led to the classification of peptides as belonging to the group of ingredients of protein nature, appropriate for use in functional foods or pharmaceutical formulations. In this study, the main peptides obtained from milk protein and the past research studies about its production and biological activities will be explained. Second, an analysis will be made on the methods to determinate the biological activities, the separation of bioactive peptides and its structure identification. All of these form the base required to obtain synthetic peptides. Finally, we explain the experimental animal and human trials done in the past years. Nevertheless, more research is required on the design and implementation of equipment for the industrial production and separation of peptides. In addition, different authors suggest that more emphasis should therefore be given to preclinical studies, proving that results are consistent and that effects are demonstrated repeatedly by several research human groups.

  4. Metabolism of growth hormone releasing peptides.

    Science.gov (United States)

    Thomas, Andreas; Delahaut, Philippe; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

    2012-12-01

    New, potentially performance enhancing compounds have frequently been introduced to licit and illicit markets and rapidly distributed via worldwide operating Internet platforms. Developing fast analytical strategies to follow these new trends is one the most challenging issues for modern doping control analysis. Even if reference compounds for the active drugs are readily obtained, their unknown metabolism complicates effective testing strategies. Recently, a new class of small C-terminally amidated peptides comprising four to seven amino acid residues received considerable attention of sports drug testing authorities due to their ability to stimulate growth hormone release from the pituitary. The most promising candidates are the growth hormone releasing peptide (GHRP)-1, -2, -4, -5, -6, hexarelin, alexamorelin, and ipamorelin. With the exemption of GHRP-2, the entity of these peptides represents nonapproved pharmaceuticals; however, via Internet providers, all compounds are readily available. To date, only limited information on the metabolism of these substances is available and merely one metabolite for GHRP-2 is established. Therefore, a comprehensive in vivo (po and iv administration in rats) and in vitro (with human serum and recombinant amidase) study was performed in order to generate information on urinary metabolites potentially useful for routine doping controls. The urine samples from the in vivo experiments were purified by mixed-mode cation-exchange solid-phase extraction and analyzed by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution/high-accuracy mass spectrometry. Combining the high resolution power of a benchtop Orbitrap mass analyzer for the first metabolite screening and the speed of a quadrupole/time-of-flight (Q-TOF) instrument for identification, urinary metabolites were screened by means of a sensitive full scan analysis and subsequently confirmed by high-accuracy product ion scan experiments. Two

  5. Study on peptide-peptide interaction using high-performance affinity chromatography and quartz crystal microbalance biosensor

    Institute of Scientific and Technical Information of China (English)

    LUO Jia; HUANG YanYan; XIONG ShaoXiang; LIU GuoQuan; ZHAO Rui

    2007-01-01

    The specific interaction between sense and antisense peptides was studied by high-performance affinity chromatography (HPAC) and quartz crystal microbalance (QCM) biosensor. Fragment 1-14 of human interferon-β (hlFN-β) was chosen as sense peptide and its three antisense peptides (AS-IFN 1,AS-IFN 2, and AS-IFN 3) were designed according to the degeneracy of genetic codes. The affinity column was prepared with sense peptide as ligand and the affinity chromatographic behavior was evaluated. Glu-substituted antisense peptide (AS-IFN 3) showed the strongest binding to immobilized sense peptide at pH 7.5. A quartz crystal microbalance-flow injection analysis (QCM-FIA) system was introduced to investigate the recognition process in real-time. The equilibrium dissociation constants between sense peptide and AS-IFN 1, AS-IFN 2 and AS-IFN 3 measured 2.08×10-4, 1.31×10-4 and 2.22×10-5 mol/L, respectively. The mechanism study indicated that the specific recognition between sense peptide and AS-IFN 3 was due to sequence-dependent and multi-modal affinity interaction.

  6. Alternative Mechanisms for the Interaction of the Cell-Penetrating Peptides Penetratin and the TAT Peptide with Lipid Bilayers

    NARCIS (Netherlands)

    Yesylevskyy, Semen; Marrink, Siewert-Jan; Mark, Alan E.

    2009-01-01

    Cell-penetrating peptides (CPPs) have recently attracted much interest due to their apparent ability to penetrate cell membranes in an energy-independent manner. Here molecular-dynamics simulation techniques were used to study the interaction of two CPPs: penetratin and the TAT peptide with 1,2-Dipa

  7. Role of SbmA in the Uptake of Peptide Nucleic Acid (PNA)-Peptide Conjugates in E. coli

    DEFF Research Database (Denmark)

    Ghosal, Anubrata; Vitali, Ally; Stach, James E M;

    2013-01-01

    Antisense PNA oligomers targeting essential genes (acpP or ftsZ) and conjugated to the delivery peptide L((KFF)(3)K) show complete growth inhibition of wild type E. coli strain (MG1655) with submicromolar MIC. In this study we show that resistant mutants generated against such PNA-peptide conjuga...

  8. PeptideBuilder: A simple Python library to generate model peptides

    Directory of Open Access Journals (Sweden)

    Matthew Z. Tien

    2013-05-01

    Full Text Available We present a simple Python library to construct models of polypeptides from scratch. The intended use case is the generation of peptide models with pre-specified backbone angles. For example, using our library, one can generate a model of a set of amino acids in a specific conformation using just a few lines of python code. We do not provide any tools for energy minimization or rotamer packing, since powerful tools are available for these purposes. Instead, we provide a simple Python interface that enables one to add residues to a peptide chain in any desired conformation. Bond angles and bond lengths can be manipulated if so desired, and reasonable values are used by default.

  9. Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides

    DEFF Research Database (Denmark)

    Kubicek-Sutherland, Jessica Z.; Lofton, Hava; Vestergaard, Martin;

    2016-01-01

    Background: The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the human innate immune system and the ramifications of prolonged bacterial exposure to AMPs...... suggest that therapeutic use of AMPs could select for virulent mutants with crossresistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated....... of sepsis. Results: AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribed antibiotics and human defence peptides. Conclusions: These findings...

  10. Tidbits for the synthesis of bis(2-sulfanylethyl)amido (SEA) polystyrene resin, SEA peptides and peptide thioesters.

    Science.gov (United States)

    Ollivier, Nathalie; Raibaut, Laurent; Blanpain, Annick; Desmet, Rémi; Dheur, Julien; Mhidia, Reda; Boll, Emmanuelle; Drobecq, Hervé; Pira, Silvain L; Melnyk, Oleg

    2014-02-01

    Protein total chemical synthesis enables the atom-by-atom control of the protein structure and therefore has a great potential for studying protein function. Native chemical ligation of C-terminal peptide thioesters with N-terminal cysteinyl peptides and related methodologies are central to the field of protein total synthesis. Consequently, methods enabling the facile synthesis of peptide thioesters using Fmoc-SPPS are of great value. Herein, we provide a detailed protocol for the preparation of bis(2-sulfanylethyl)amino polystyrene resin as a starting point for the synthesis of C-terminal bis(2-sulfanylethyl)amido peptides and of peptide thioesters derived from 3-mercaptopropionic acid. PMID:24254655

  11. Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos

    DEFF Research Database (Denmark)

    Kristensen, Mie; Birch, Ditlev; Mørck Nielsen, Hanne

    2016-01-01

    -penetrating peptides (CPPs) constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB). CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide...... or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo. Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific...... barrier and the target cell. Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are commonly employed to prolong the CPP half-life. The mechanisms by which CPPs translocate...

  12. Peptide receptor radionuclide therapy of neuroendocrine tumours.

    Science.gov (United States)

    Brabander, Tessa; Teunissen, Jaap J M; Van Eijck, Casper H J; Franssen, Gaston J H; Feelders, Richard A; de Herder, Wouter W; Kwekkeboom, Dik J

    2016-01-01

    In the past decades, the number of neuroendocrine tumours that are detected is increasing. A relative new and promising therapy for patients with metastasised or inoperable disease is peptide receptor radionuclide therapy (PRRT). This therapy involves an infusion of somatostatin analogues linked to radionuclides like Yttrium-90 or Lutetium-177. Objective response rates are reported in 15-35%. Response rates may vary between type of tumour and radionuclide. Besides the objective response rate, overall survival and progression free survival increase significantly. Also, the quality of life improves as well. Serious side-affects are rare. PRRT is usually well tolerated, also in patients with extensive metastasised disease. Recent studies combined PRRT with other types of therapies. Unfortunately no randomised trials comparing these strategies are available. In the future, more research is needed to evaluate the best therapy combinations or sequence of therapies. PMID:26971847

  13. Peptides whose uptake by cells is controllable

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Tao; Tsien, Roger Y

    2014-02-04

    A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

  14. Pro-Moieties of Antimicrobial Peptide Prodrugs

    Directory of Open Access Journals (Sweden)

    Eanna Forde

    2015-01-01

    Full Text Available Antimicrobial peptides (AMPs are a promising class of antimicrobial agents that have been garnering increasing attention as resistance renders many conventional antibiotics ineffective. Extensive research has resulted in a large library of highly-active AMPs. However, several issues serve as an impediment to their clinical development, not least the issue of host toxicity. An approach that may allow otherwise cytotoxic AMPs to be used is to deliver them as a prodrug, targeting antimicrobial activity and limiting toxic effects on the host. The varied library of AMPs is complemented by a selection of different possible pro-moieties, each with their own characteristics. This review deals with the different pro-moieties that have been used with AMPs and discusses the merits of each.

  15. Biofilm Induced Tolerance Towards Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Folkesson, Anders; Haagensen, Janus Anders Juul; Zampaloni, Claudia;

    2008-01-01

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We address the question of how biofilm organization affects antibiotic susceptibility. We established Escherichia coli biofilms with differential structural organization due...... to the presence of IncF plasmids expressing altered forms of the transfer pili in two different biofilm model systems. The mature biofilms were subsequently treated with two antibiotics with different molecular targets, the peptide antibiotic colistin and the fluoroquinolone ciprofloxacin. The dynamics...... of microbial killing were monitored by viable count determination, and confocal laser microscopy. Strains forming structurally organized biofilms show an increased bacterial survival when challenged with colistin, compared to strains forming unstructured biofilms. The increased survival is due to genetically...

  16. Coexistence of peptides with classical neurotransmitters.

    Science.gov (United States)

    Hökfelt, T; Millhorn, D; Seroogy, K; Tsuruo, Y; Ceccatelli, S; Lindh, B; Meister, B; Melander, T; Schalling, M; Bartfai, T

    1987-07-15

    In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, gamma-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than one messenger molecule. The exact functional role of such coexisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more complex than perhaps hitherto assumed. PMID:2885215

  17. Some arachnidan peptides with potential medical application

    Directory of Open Access Journals (Sweden)

    ME De Lima

    2010-01-01

    Full Text Available The search for new active drugs that can alleviate or cure different diseases is a constant challenge to researchers in the biological area and to the pharmaceutical industry. Historically, research has focused on the study of substances from plants. More recently, however, animal venoms have been attracting attention and studies have been successful in addressing treatment of accidents. Furthermore, venoms and their toxins have been considered good tools for prospecting for new active drugs or models for new therapeutic drugs. In this review, we discuss some possibilities of using different toxins, especially those from arachnid venoms, which have shown some potential application in diseases involving pain, hypertension, epilepsy and erectile dysfunction. A new generation of drugs is likely to emerge from peptides, including those found in animal venoms.

  18. Phytochelatins: peptides involved in heavy metal detoxification.

    Science.gov (United States)

    Pal, Rama; Rai, J P N

    2010-03-01

    Phytochelatins (PCs) are enzymatically synthesized peptides known to involve in heavy metal detoxification and accumulation, which have been measured in plants grown at high heavy metal concentrations, but few studies have examined the response of plants even at lower environmentally relevant metal concentrations. Recently, genes encoding the enzyme PC synthase have been identified in plants and other species enabling molecular biological studies to untangle the mechanisms underlying PC synthesis and its regulation. The present paper embodies review on recent advances in structure of PCs, their biosynthetic regulation, roles in heavy metal detoxification and/or accumulation, and PC synthase gene expression for better understanding of mechanism involved and to improve phytoremediation efficiency of plants for wider application.

  19. Crystallizing Transmembrane Peptides in Lipidic Mesophases

    Energy Technology Data Exchange (ETDEWEB)

    Höfer, Nicole; Aragão, David; Caffrey, Martin (Trinity)

    2011-09-28

    Structure determination of membrane proteins by crystallographic means has been facilitated by crystallization in lipidic mesophases. It has been suggested, however, that this so-called in meso method, as originally implemented, would not apply to small protein targets having {le}4 transmembrane crossings. In our study, the hypothesis that the inherent flexibility of the mesophase would enable crystallogenesis of small proteins was tested using a transmembrane pentadecapeptide, linear gramicidin, which produced structure-grade crystals. This result suggests that the in meso method should be considered as a viable means for high-resolution structure determination of integral membrane peptides, many of which are predicted to be coded for in the human genome.

  20. Peptides whose uptake by cells is controllable

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Tao; Olson, Emilia S.; Whitney, Michael; Tsien, Roger

    2015-07-07

    A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.