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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Ribonucleotide Reductase: A Mechanistic Portrait of Substrate Analogues Inhibitors

Author(s): M.A.S. Perez, N.M.F.S.A. Cerqueira, P.A. Fernandes and M.J. Ramos

Volume 17, Issue 26, 2010

Page: [2854 - 2872] Pages: 19

DOI: 10.2174/092986710792065054

Price: $65


Ribonucleotide reductase (RNR) is the key enzyme in the biosynthesis of deoxyribonucleotides. Several different strategies for inactivation of RNRs have been reported, including the use of substrate analogues as mechanism-based inhibitors. This article undergoes a critical analysis on the current status of ribonucleotide reductase inhibitory mechanisms by substrate analogues highlighting experimental and theoretical/computational approaches. We have summarized a general portrait of the inhibitory mechanisms and classified the nucleoside analogue inhibitors in three main classes. The critical analysis undertaken will contribute in finding new and more effective ways of inhibiting RNR.

Keywords: Ribonucleotide reductase, RNR, substrate analogues, gemcitabine, inhibitors, computational chemistry, density functional theory

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