Mechanism-based inhibition of ribonucleotide reductases: new mechanistic considerations and promising biological applications.

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Abstract
Ribonucleotide reductases (RNRs) perform the de novo biosynthesis of 2′-deoxynucleoside 5′-(di or tri)phosphates. Inhibition of RNRs removes a crucial source of genetic components and enhances the probability of salvage incorporation of analogues into DNA. Several laboratories have clarified aspects of the reaction cascades initiated by generation of substrate nucleotide C3′ free radicals by RNRs. New considerations for radical-mediated mechanism-based inhibition and biological applications are discussed.