Differentiation of α-COOH from γ-COOH in glutamic acid by N-phosphorylation

Abstract

The biomimic reactions of N-phosphoryl amino acids are very important in the study of many biochemical processes. It was found that the α-COOH group, and not the γ-COOH, was involved in the ester exchange on phosphorus experimentally. The reactions, had been proposed to be related to intramolecular penta-coordinate phosphoric–carboxylic mixed anhydrides. N-Dimethylphosphoryl glutamic acid (DMP-Glu) was selected as model compound to study the reactivity difference between the α-COOH and γ-COOH group. From MNDO calculations, the energy of the penta-coordinate phosphoric intermediates containing five-membered ring from α-COOH was 40.8 kJ/mol lower than that of the seven-membered one from γ-COOH. This result was in agreement with those from HF/6-31G ∗∗ and B3LYP/6-31G ∗∗ calculations. Theoretical three-dimensional potential energy surface of forming the intermediates predicted that the transition states 4 and 5 involving α-COOH or γ-COOH group had energy barriers of Δ E=196.1 and 216.9 kJ/mol, respectively. So the α-COOH could be differentiated from γ-COOH intramolecularly in glutamic acid by N-phosphorylation.