Theoretical Studies of the Conformational Properties of Ribavirin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1976 Dec 1

PMID 1069980

Citations 5

Authors

D L Miles

D W Miles

P Redington

H EYRING

Affiliations

Soon will be listed here.

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.

Citing Articles

Crystallization Selectivity of Ribavirin Solution and Amorphous Phase.

Li F, Chen S, Hu H, Liang C, Sun S, Jin C Molecules. 2023; 28(17).

PMID: 37687147 PMC: 10488721. DOI: 10.3390/molecules28176320.

Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations of the Crystalline Polymorphs of the Antiviral Drug Ribavirin.

Davis M, Korter T Mol Pharm. 2022; 19(9):3385-3393.

PMID: 35950677 PMC: 9449968. DOI: 10.1021/acs.molpharmaceut.2c00509.

Interferon induction: a conformational hypothesis.

Miles D, Miles D, EYRING H Proc Natl Acad Sci U S A. 1979; 76(3):1018-21.

PMID: 286290 PMC: 383178. DOI: 10.1073/pnas.76.3.1018.

Conformation of nucleosides: circular dichroism study on the syn-anti conformational equilibrium of 2-substituted benzimidazole nucleosides.

Miles D, Townsend L, Miles D, EYRING H Proc Natl Acad Sci U S A. 1979; 76(2):553-6.

PMID: 284380 PMC: 382986. DOI: 10.1073/pnas.76.2.553.

Conformational basis for the activation of adenylate cyclase by adenosine.

Miles D, Miles D, EYRING H Proc Natl Acad Sci U S A. 1977; 74(6):2194-8.

PMID: 267918 PMC: 432135. DOI: 10.1073/pnas.74.6.2194.

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