Theoretical studies of the conformational properties of ribavirin.

Abstract:

:One of the factors required for the antiviral activity of the synthetic nucleoside, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), is the ability of the molecule to adopt the substrate conformation specified by the enzyme for which it is a competitive inhibitor, inosine 5'-phosphate dehydrogenase (IMP:NAD+ oxidoreductase, EC 1.2.1.14). The calculated glycosidic minimum for ribavirin is the high syn conformation, which is in agreement with experimental determinations of the molecule's solution conformation. The similarity in solution between the conformation of the active ribavirin molecule and the conformation of its inactive 5-methyl and 5-chloro derivatives indicate that some other substrate conformation is specified by the enzyme. The high anti conformation, found by these calculations to be close in energy to the high syn minimum, is postulated to be the active conformation required by the enzyme. The inactivity of the 5-methyl and 5-chloro derivatives is attributed to the much greater stability of these derivatives in the inactive high syn conformation.

authors

Miles DL,Miles DW,Redington P,Eyring H

doi

10.1073/pnas.73.12.4257

keywords:

subject

Has Abstract

pub_date

1976-12-01 00:00:00

pages

4257-60

issue

12

eissn

0027-8424

issn

1091-6490

journal_volume

73

pub_type

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