Phosphoryl group differentiating alpha-amino acids from beta- and gamma-amino acids in prebiotic peptide formation

Abstract

in recent years beta-amino acids have increased their importance enormously in defining secondary structures of beta-peptides. Interest in beta-amino acids raises the question: Why and how did nature choose alpha-amino acids for the central role in life? In this article we present experimental results of MS and P-31 NMR methods on the chemical behavior of N-phosphorylated alpha-alanine, beta-alanine, and gamma-amino butyric acid in different solvents. N-Phosphoryl alpha-alanine can self-assemble to N-phosphopeptides either in water or in organic solvents, while no assembly was observed for beta- or gamma-amino acids. An intramolecular carboxylic-phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from alpha-alanine (2a-c), with five-membered ring, and five isomers of IMCPA derived from beta-alanine (4a-e), with six-membered ring, were calculated with density functional theory at the B3LYP/6-31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N-phosphoryl alpha-alanine. Both experimental and theoretical studies indicate that the structural difference among alpha-, beta-, and gamma-amino acids can be recognized by formation of IMCPA after N-phosphorylation. (C) 2003 Wiley Periodicals, Inc.