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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.

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: September 1, 2010

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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