A synthetic scheme for preparation of (Gly-Pro)n, (Pro-Gly)n (n = 2, 3), and (Pro-Gly-Pro)n (n = 1, 2) peptides was elaborated. The effect of the synthesized peptides and the Gly-Pro and Pro-Gly dipeptides on survival of cultured cells of PC12 rat pheochromocytoma was studied under the conditions of oxidative stress induced by brief incubation of the cells with hydrogen peroxide. Peptides of the general formula (Gly-Pro)n and the Pro-Gly-Pro peptide at a concentration of 0.2-100 microM were shown to decrease the number of damaged cells. The Gly-Pro peptide was the most active and decreased the number of damaged cells by 49% on average at a concentration of 100 microM.
The potentialities and restrictions of chemoenzymatic approach to the synthesis of new structural analogues of antiviral drug Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) have been determined. Syntheses of various amides of 1H-1,2,4-triazole-3-carboxylic acid and its 5-substituted analogues, prospective substrates of purine nucleoside phosphorylase (PNP), have been reported. The comparative effectiveness of the methods for obtaining amides aforementioned and also the methods for introducing functional groups to the C5 position of the heterocyclic system has been studied. New Ribavirin analogues bearing various substituents in the carboxamide group have been synthesized. The biotechnological method for the preparation of 1-beta-D-ribofuranosyl- 1,2,4-triazole-3-carbonitrile used as the intermediate in the synthesis of Viramidine, a contemporary Ribavirin analogue, has been developed.
Viral adsorption inhibitors represent new generation of antiviral drugs, which can be applied for the treatment of HIV infection. Given review presents the different classes of HIV entry inhibitors grouped by the processes they are targeted: the binding of viral glycoprotein gp120 with cellular receptor CD4, the following interaction of gp120 with the chemokine receptors CCR5 or CXCR4, the formation of six-helix bundle gp41 needed for the viral and cellular membrane fusion.
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