STRUCTURE - ANTIVIRAL ACTIVITY CORRELATION OF CONFORMATIONALLY RESTRICTED NUCLEOSIDE ANALOGS. Gurskaya G.V.,* Zavodnik V.E., Krayevsky A.A., Engelhardt Institute of Molecular Biology, Russian, Academy of Sciences, 32 Vavilov Str., 117984 Moscow, Russia, *Karpov Institute of Physical Chemistry, 10 Obukha Str. 103064 Moscow, Russia

Recent search for new drugs revealed some modified nucleosides with antiretroviral activity, including the anti-HIV. The molecular mechanism of such activity is based on incorporation of their 5'-triphosphates into the new DNA strand during catalysis by DNA-polymerases and viral reverse transcriptases and ensuing interruption (termination) of elongation. In the case of viruses this results in inhibition of their reproduction. The modified nucleoside triphosphate affinity to each type of DNA-polymerase is determined both by the chemical nature of substituent groups in the nucleoside moiety and molecular conformation of nuc-leoside analogs.To investigate the structure - activity correlations, we studied X-ray structures of some conformationally restricted modified nucleoside series : 3'- methyl nucleoside analogs; 2',3'-dideoxy-2',3'- didehydronucleosides; nucleosides containing in their furanose cycles an additional three-membered fused ring in endo- or exorientation, as well as conformationally restricted compounds with an additional oxymethyl group at 4'-position. It can be suggested that the con-formation of such conformationally restricted nucleosides is preserved in the DNA-synthesizing complexes, and mimicks the active conformation of a native substrate if conformationally restricted nucleotides reveal substrate properties.