Ab initio studies of some amino acid residue complexes with 4-mercaptopyridine as a model for Thymitaq (AG337), an inhibitor of thymidylate synthase Journal Article
| Authors: | Sapse, D. S.; Tong, Y.; Bertino, J. R.; Sapse, A. M. |
| Article 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. |
| Keywords: | human tissue; unclassified drug; human cell; pyridines; binding affinity; enzyme inhibition; amino acid substitution; protein binding; drug structure; cancer inhibition; geometry; thermodynamics; isoleucine; binding sites; alanine; amino acids; thymidylate synthase inhibitor; thymidylate synthase; structure analysis; quinazolines; electrons; models, chemical; glycine; amino acid analysis; hydrogen; raltitrexed; quantum chemistry; nolatrexed; ions; benzene; acetamides; human; priority journal; article; methane; 4 mercaptopyridine; isopentane; metesind glucuronate; pentanes |
| Journal Title: | Cancer Investigation |
| Volume: | 17 |
| Issue: | 6 |
| ISSN: | 0735-7907 |
| Publisher: | Informa Healthcare |
| Date Published: | 1999-01-01 |
| Start Page: | 396 |
| End Page: | 401 |
| Language: | English |
| PUBMED: | 10434950 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
