5-Nitro-2'-deoxyuridine 5'-Phosphate: A Mechanism-Based Inhibitor of Thymidylate Synthetase
5-Nitro-2'-deoxyuridine 5'-phosphate (2) was found to be a mechanism-based affinity label for thymidylate synthetase purified from amethopterin resistant Lactobacillius casei.The inhibition proceeds in two steps via the initial formation of the noncovalent complex 3 (Ki = 510-7 M) which is converted to the covalent complex 4. The net dissociation constant for the overall sequence is 6.510-10 M, a value predicted from model studies of the bimolecular reaction of 2-mercaptoethanol with 5-nitrouridine or 2.
Maggiora, Linda,Chang, Charles C. T.-C.,Torrence, Paul F.,Mertes, Mathias P.