Cancer Investigation 1999-01-01

Ab initio studies of some amino acid residue complexes with 4-mercaptopyridine as a model for thymitaq (AG337), an inhibitor of thymidylate synthase.

D S Sapse, Y Tong, J R Bertino, A M Sapse

Index: Cancer Invest. 17(6) , 396-401, (1999)

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Abstract

The complex formed by isopentane, as a model for the isoleucine residue present in the wild-type thymidylate synthase, with 4-mercaptopyridine as a fragment of the thymidylate synthase inhibitor Thymitaq (AG337) is investigated with ab initio quantum chemical calculations at Hartree-Fock and MP2 levels, using the 3-21G* basis set. The binding energy is compared with the binding energies of 4-mercaptopyridine with amino acid residues found in mutant thymidylate synthase enzymes. As compared with isoleucine, alanine and glycine do not show binding, in agreement with enzyme-inhibition results.