Biomedical subjects
Publications and source records attributed to R Zutshi.
A novel strategy was used to irreversibly inhibit HIV-1 protease. The inhibitor was designed to form a disulfide bond with Cys95, present at the dimerization interface of HIV-1 protease. The inhibitor was shown to be active against HIV-1 protease with K(inact) = 3.7 microM and V(inact) = 0.012 min(-1).
Self-replication has been demonstrated in synthetic chemical systems based on oligonucleotides, peptides and complementary molecules without natural analogues. However, within a living cell virtually no molecule catalyses its own formation, and the search for chemical systems in which both auto- and cross-catalysis can occur has therefore attracted wide interest. One such system, consisting of two self-replicating peptides that catalyse each other's production, has been reported. Here we describe a four-component peptide system that is capable of auto- and cross-catalysis and allows for the selective amplification of one or more of the products by changing the reaction conditions. The ability of this system selectively to amplify one or more molecules in response to changes in environmental conditions such as pH or salt concentration supports the suggestions that self-replicating peptides may have played a role in the origin of life.
Endothiopeptide inhibitors of HIV-1 protease were synthesized by chemical and enzymatic methods to individually replace each backbone amide bond in 1 with a thioamide-linkage. Interestingly, agent 7, which contains a thioamide-linkage between the P2' and P3' positions of 1, was the most potent, competitive inhibitor of HIV-1 protease with a Ki of 3.4 microM.
Protein-protein association is found throughout mechanisms of cellular growth and differentiation, and viral replication. Inhibiting the assembly of protein complexes, therefore, presents itself as a novel means of inhibition for a wide variety of cellular and viral events. Peptides and small molecules that modify the overall quaternary structure of a selection of receptor-ligand interactions and oligomeric viral enzymes have been developed recently.
PURPOSE/METHODS: A cross-sectional study was carried out to review the ocular status of 2,063 diabetic patients in Oman. A part of this study is presented to highlight the magnitude and determinants of glaucoma. The study also recommends policies for comprehensive care of glaucoma among diabetic patients. The ocular pressure, disc changes, and field changes were noted by ophthalmologists. The diabetes profile was noted by physicians. RESULTS: The rate of glaucoma among diabetic patients was 8.87% (95% CI 8.12 to 9.62). Male diabetic patients had significantly higher rates of glaucoma than female diabetic patients. The rate was significantly higher in higher age groups. The mean ocular pressure in glaucomatous eyes was 28.6 mm Hg. The rate was not significantly different in patients with type I and type II diabetes (RR 1.03 [95% CI 0.61 to 1.79]). The risk of visual disability was higher among diabetic patients with glaucoma than diabetic patients without glaucoma (RR 1.56 [95% CI 1.14 to 2.13]). CONCLUSIONS: Ocular pressure measurement could be a simple and reliable first-level screening tool. Diabetic patients with glaucoma should be given special care to reduce visual disability. All patients with diabetes should be thoroughly checked periodically to rule out glaucoma.
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