ABSTRACT
The constrained alpha-helical structure of a C-peptide is useful for enhancing anti-HIV-1 activity. The i and i+3 positions in an alpha-helical structure are located close together, therefore D-Cys (dC) and L-Cys (C) were introduced at the positions, respectively, to make a dC-C disulfide bond in 28mer C-peptides. Accordingly, this study tested whether a dC-C disulfide bond would increase the alpha-helicity and anti-HIV-1 activity of peptides. A C-peptide can be divided into three domains, the N-terminal hydrophobic domain (HPD), middle interface domain (IFD), and C-terminal hydrogen domain (HGD), based on the binding property with an N-peptide. In general, the dC-C modifications in HPD enhanced the anti-HIV-1 activity, while those in IFD and HGD resulted in no or much less activity. The modified peptides with no activity clearly showed much less alpha-helicity than the native peptides, while those with higher activity showed an almost similar or slightly increased alpha-helicity. Therefore, the present results suggest that the introduction of a dC-C bridge in the N-terminal hydrophobic domain of a C-peptide may be useful for enhancing the anti-HIV-1 activity.
Subject(s)
Humans , Amino Acid Sequence , Anti-HIV Agents/chemical synthesis , Cell Line , Circular Dichroism , Cysteine/chemistry , Disulfides/chemistry , HIV Envelope Protein gp41/chemistry , HIV-1/drug effects , Inhibitory Concentration 50 , Models, Molecular , Molecular Sequence Data , Peptides/chemical synthesis , Protein Structure, Secondary , Protein Structure, Tertiary , Structure-Activity RelationshipABSTRACT
Several [2-phenyl-4(3H)-oxo-3-quinazolinylamino]-N-substituted- arylacetamides (1a-j) have been synthesized and tested at the National Cancer Institute, Bethesda, Maryland, USA, for their anti-HIV activity against susceptible human host cells (CEM cell line) over a wide range of concentrations (6.35 x 10(-8) to 2.00 x 10(-4) M). The highest protection observed is 45.67%. The structures of these compounds have been established on the basis of elemental analysis and spectral data.
Subject(s)
Anti-HIV Agents/chemical synthesis , Cell Line , Humans , Microbial Sensitivity Tests , Quinazolines/chemical synthesisABSTRACT
Several 2,4-diaminopyrimidines have been synthesized and tested for their anticancer and anti-HIV activities. Out of these, eight compounds displayed significant activity against leukemia, melanoma, non-small cell and CNS cancer. Two compounds were active against leukemia P388. One compound has been found to be moderately active as compared to AZT.