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

The biomimic reactions of N-phosphoryl amino acids are very important in the study of many biochemical processes. It was found that the alpha -COOH group, and not the gamma -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 alpha -COOH and gamma -COOH group. From MNDO calculations, the energy of the penta-coordinate phosphoric intermediates containing five-membered ring from alpha -COOH was 40.8 kJ/mol lower than that of the seven-membered one from gamma -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 alpha -COOH or gamma -COOH group had energy barriers of DeltaE = 196.1 and 216.9 kJ/mol, respectively. So the alpha -COOH could be differentiated from gamma -COOH intramolecularly in glutamic acid by N-phosphorylation. (C) 2001 Elsevier Science B.V. All rights reserved.