title: Rational design of selective antimetabolites of DNA-thymine biosynthesis: 5-propynylpyrimidine nucleoside derivatives.
abstract: A novel series of 5-propynylpyrimidine nucleosides are proposed as potential antimetabolites of DNA-thymine biosynthesis. This proposal is based on the results of detailed mechanistic analyses of the molecular interactions between dTMP synthase and its inhibitors. It is proposed that a propynyl side-chain at the 5-position of dUMP, bearing an appropriate leaving group, would cause irreversible inactivation of dTMP synthase, which would not require the presence of the cofactor, CH2H4folate.
authors.affiliation: Department of Medicinal Chemistry, State University of New York at Buffalo 14260, USA.
authors.forename: T I
authors.initials: TI
authors.lastname: Kalman
authors.forename: Z
authors.initials: Z
authors.lastname: Nie
mesh_terms: D004247:DNA / Q000096:biosynthesis / Q000737:chemistry*; D015195:Drug Design; D008958:Models, Molecular; D019384:Nucleic Acid Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D013941:Thymine / Q000737:chemistry*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D011741:Pyrimidine Nucleosides; D004247:DNA; D013940:Thymidylate Synthase; D013941:Thymine