Enantioselectivity of the antiviral effects of nucleoside analogues

Natural D-nucleosides are no longer the sole basis for designing effective antiviral analogues, Many antivirals with an opposite (L) configuration wer e reported, with lamivudine being the most notable example. In contrast, ca rbocyclic nucleoside analogues are significantly more enantioselective, and enantiomers with a configuration corresponding to D-nucleosides are usuall y favored. In the series of acyclic nucleoside analogues, the antiviral pot ency resides in a single enantiomer. Allenic analogues with an axial dissym metry are R-enantioselective, in contrast to structurally similar methylene cyclopropanes, where the enantioselectivity strongly depends on the type of virus. Enantioselectivity of acyclic nucleotide analogues exhibits a more complex pattern. The overall enantioselectivity of the antiviral effects is determined by responses of activating (phosphorylating) enzymes, as well a s target DNA polymerases (reverse transcriptase), toward enantiomers of act ive analogues. (C) 2000 Elsevier Science Inc. All rights reserved.