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

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.

journal_name

Cancer Invest

journal_title

Cancer investigation

authors

Sapse DS,Tong Y,Bertino JR,Sapse AM

doi

10.3109/07357909909021431

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

396-401

issue

6

eissn

0735-7907

issn

1532-4192

journal_volume

17

pub_type

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