title: 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.
authors.affiliation: Barnard College of Columbia University, New York, New York, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Sapse
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.forename: J R
authors.initials: JR
authors.lastname: Bertino
authors.forename: A M
authors.initials: AM
authors.lastname: Sapse
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D001554:Benzene / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004583:Electrons; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism; D007477:Ions; D008697:Methane / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D010420:Pentanes / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013816:Thermodynamics; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000081:Acetamides; D000596:Amino Acids; D007477:Ions; D010420:Pentanes; D011725:Pyridines; D011799:Quinazolines; C042861:4-thiopyridine; D006859:Hydrogen; C030686:acetamide; D013940:Thymidylate Synthase; D001554:Benzene; C099178:nolatrexed; D008697:Methane; C067038:isopentane