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.
journal_name
Proc Natl Acad Sci U S Aauthors
Miles DL,Miles DW,Redington P,Eyring Hdoi
10.1073/pnas.73.12.4257keywords:
subject
Has Abstractpub_date
1976-12-01 00:00:00pages
4257-60issue
12eissn
0027-8424issn
1091-6490journal_volume
73pub_type
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