Exploring the potential of 3′-O-carboxy esters of thymidine as inhibitors of ribonuclease A and angiogenin
In this study, compounds with a carboxy ester in lieu of the phosphate ester at the 3′-position have been employed to inhibit the ribonucleolytic activity of ribonuclease A (RNase A). Phosphates at the 3′-position of pyrimidine bases are well-known inhibitors of the protein. We have investigated the inhibition of RNase A by 3′-O-carboxy esters of thymidine. The compounds behave as competitive inhibitors with inhibition constants ranging from 42 to 95 μM. The mode of inhibition has also been confirmed by 1H NMR studies of the active site histidines of RNase A. Docking studies have further substantiated the experimental results. The compounds are also found to inhibit the ribonucleolytic activity of angiogenin, a homologous protein and potent inducer of blood vessel formation.
An entry to unusual classes of nucleoside analogues
Nucleosides 6a,m 6b and 16-18 having additional carbocycle or oxygen heterocycle fused to the ribose moiety have been synthesized by two routes. While 6a and 6b could be obtained from thymidine using 1,3-dipolar cycloaddition approach, Vorbruggen reaction on appropriate preformed carbocyclic derivatives furnished 16-18.
Bar, Narayan C.,Patra, Ranjan,Achari, Basudeb,Mandal, Sukhendu B.
p. 4727 - 4738
(2007/10/03)
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