Activities of α-COOH vs γ-COOH in N-Phosphoryl Amino Acids: A Theoretical Study

Abstract

The biomimic reactions of N-phosphoryl amino acids are very important in the study of many biochemical processes, such as origin of proteins and phosphorylation of amino acid residues in the proteins. The differences in reactivities between α-COOH and γ-COOH in phosphoryl amino acids were studied by ab initio and density functional methods. The pentacoordinate phosphoric intermediates 2 containing five-membered rings were predicted to be more stable than 3 with seven-membered rings. For intermediates 3, the isomers with apical-equatorial ring spanning arrangement were predicted to be more stable than those with diequatorial ring spanning arrangement. At the B3LYP/6-31G** level, intermediates 2 were 66.56 kJ/mol lower in energy than 3. It was shown that the transition states 4 and 5 involving an α-COOH or γ-COOH group had energy barriers of ΔE = 57.59 kJ mol-1 and 120.93 kJ mol-1, respectively. The theoretical calculations suggested that the α-COOH group could be differentiated from the γ-COOH intramolecul...