A quantum chemical study on the mechanism of glycinamide ribonucleotide transformylase inhibitor: 10-Formyl-5,8,10-trideazafolic acid

• Published in: Biophysical chemistry 2005-12, Vol.118 (2), p.78-83
• Main Authors: Qiao, Qing-An, Jin, Yueqing, Yang, Chuanlu, Zhang, Zhihong, Wang, Meishan
• Format: Article
• Language: English
• Subjects: 10-Formyl-5,8,10-trideazafolic acid; Catalysis; Chemical Phenomena; Chemistry, Physical; Density Functional Theory (DFT); Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; GAR Tfase inhibitor; Glutamates - chemistry; Glutamates - pharmacology; Glycine - analogs & derivatives; Glycine - chemical synthesis; Glycine - chemistry; Models, Chemical; Molecular Structure; Phosphoribosylglycinamide Formyltransferase - antagonists & inhibitors; Quantum Theory; Quinazolines - chemistry; Quinazolines - pharmacology; Ribonucleotides - chemical synthesis; Ribonucleotides - chemistry; Stereoisomerism
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/j.bpc.2005.07.001

A density functional theory (DFT) study is presented on the reaction mechanism of glycinamide ribonucleotide (GAR) with 10-formyl-5,8,10-trideazafolic acid (10f-TDAF), which is an inhibitor designed for GAR transformylase (GAR Tfase). There are three different paths for this system and the results indicate that inhibitor 10f-TDAF can form a very stable intermediate with the substrate GAR or generate an imine bond with GAR by elimination of water. The results have verified the presumption from available experiments and implied that 10f-TDAF would be an important target for anti-neoplastic intervention.