Ribonucleotide reductase, mechanism-based inactivation

Since 1976 a number of 2 -substituted 2 -deoxynucleoside 5 -diphosphates have been shown to be mechanism-based inactivators of the ribonucleotide reductases from a variety of sources (Table I). This work was extended by Stubbe and Kozarich 50, 51), who studied the reaction of several 2 -halo-substituted 2 -deoxynucleoside 5 -diphosphates with RDPR. Incubation of RDPR with CIUDP, 2 -deoxy-2 -fluoroadenosine 5 -diphosphate (FADP), or 2 -deoxy-2 -fluorocytidine 5 -diphosphate (FCDP) resulted in time-dependent enzyme inactivation, concomitant and stoichiometric loss of all substituents from the ribose moiety, increase in the UV-Vis absorbance of the protein near 320 nm, and... 

In a study related to the mechanism of inactivation of ribonucleotide diphosphate reductase (RDPR) by 2 -deoxy-2 -substituted nucleotide analogues, it was found that treatment of nucleosides of type 57 (B=Ura, Ade, X=I, Br, Cl, SMe, N3) with tributylstannane and AIBN gave the d4 products 58, whilst with X=F, OMs or OTs, the 3 -deoxysystem 59 was the product. The results pointed to the loss of radicals rather than anions from C-2 during mechanism-based inactivation of RDPR, and the authors suggest some modifications to Stubbe s mechanistic proposals. ... 

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