Pa. Furman et al., THE EFFECT OF ABSOLUTE-CONFIGURATION ON THE ANTI-HIV AND ANTI-HBV ACTIVITY OF NUCLEOSIDE ANALOGS, Antiviral chemistry & chemotherapy, 6(6), 1995, pp. 345-355
This review concerns the effect of stereoisomerism on the selective ac
tivity of anti-HIV and anti-HBV nucleoside analogues. The synthesis of
a number of nucleoside analogues with anti-HIV and anti-HBV activity
yields mixtures of 1-beta-D and 1-beta-L stereoisomers. Anti-HIV and a
nti-HBV activity is associated primarily with one of the two enantiome
rs and the more potent activity does not always reside with the 1-beta
-D configuration characteristic of natural nucleosides. In the case of
HIV, the origin of this stereoselectivity appears to be the result of
differential metabolism of the analogues and not due to differential
inhibition of the target enzyme; the HIV reverse transcriptase. Howeve
r, mutations at position 184 of the HIV-RT does result in stereoselect
ive inhibition of the enzyme. On the other hand, with HBV, there is al
so a stereoselective inhibition of the HBV DNA polymerase, where the 5
'-triphosphate of the 1-beta-L enantiomer is the more potent inhibitor
.