The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA...Full Text Available
Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...
Radiopharmaceuticals for brain imaging are used for the detection of ischemia, tumours and dementia associatied with disorders of the blood flow in the brain. The current radiopharmaceuticals for brain imaging have various limitations: 2-(F-18)fluoro-2-deoxyglucose (F-18-FDG) has a very short half-life. The physical properties of di-#beta#-(piperidinoethyl)-(Se-75)selenide (Se-75-PIPSE) and di-#beta#-(morpholinoethyl)-(Se-75)-selenide (Se-75-MOSE) are not ideal. Thallium-201 diethyldithricarbamate (T1-201-DDC) has unfavourable nuclidic characteristics, limited availability, a long half-life and high cost. I-123 in N-isopropyl-p-iodoamphetamine (I-123-IMP) and N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (I-123-HIPDM) are not freely available and are expensive. N-13-labelled ammonia has a very short half-life. Technetium-99m hexamethylpropyleneamineoxime (Tc-99m-HM-PAO) is unstable both in vitro and in vivo and has a low brain-to-blood ...