Phosphoryl group differentiating ?-amino acids from ?- and ?-amino acids in prebiotic peptide formation

In recent years β-amino acids have increased their importance enormously in defining secondary structures of β-peptides. Interest in β-amino acids raises the question: Why and how did nature choose α-amino acids for the central role in life? In this article we present experimental results of MS and 31P NMR methods on the chemical behavior of N-phosphorylated α-alanine, β-alanine, and γ-amino butyric acid in different solvents. N-Phosphoryl α-alanine can self-assemble to N-phosphopeptides either in water or in organic solvents, while no assembly was observed for β- or γ-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 α-alanine (2a–c), with five-membered ring, and five isomers of IMCPA derived from β-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 α-alanine. Both experimental and theoretical studies indicate that the structural difference among α-, β-, and γ-amino acids can be recognized by formation of IMCPA after N-phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003