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Ribonucleotide Reductase: A Mechanistic Portrait of Substrate Analogues Inhibitors

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

Document Type: Research Article

Affiliations: REQUIMTE, Faculdade de Ciencias, Universidade do Porto, 4169-007 Porto, Portugal.

Publication date: 2010-09-01

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