The Classification of Twenty Common Amino Acid Residues in Protected Peptides by Their β-Sheet-Structure-Stabilizing Potentials, SPβ, and Its Application to Peptide Synthesis

Abstract

Abstract A host-guest approach was devised to evaluate the β-sheet-structure-stabilizing potentials, SPβ, of the 20 common amino acid residues in protected peptides whose side-chain functional groups were protected by suitable groups commonly used in peptide synthesis. The β-sheet structure of host-guest pentapeptides, namely, Boc–X–Val–Asp(OBzl)–Ala–Gly–OPac and Boc–X–Ala–Glu(OBzl)–Leu–Gly–OPac in which X stands for guest amino acid residues, was easily disrupted in CH2Cl2 by increasing amounts of DMSO. The disrupted behaviors were strongly dependent on the nature of the guest amino acid residues and the 20 guest amino acid residues could be classified into six groups. Therefore, we arbitrarily defined SPβ as values of one to six. A method for estimating the β-sheet-structure stability of protected peptides by their arithmetic average <SPβ> values was proposed, and it was applied to peptide synthesis. The significance of the estimation method in the design of synthetic routes for peptides and proteins is briefly discussed.