Preorganized Cyclic α,α-Disubstituted α-Amino Acids Bearing Functionalized Side Chains That Act as Peptide-Helix Inducers

Abstract

Preorganized cyclic α,α-disubstituted α-amino acids (dAA) bearing functionalized side chains that acted as peptide-helix inducers, which could be used for solid-phase peptide synthesis, were designed and synthesized. Furthermore, a helical octapeptide with the following amino acid sequence was prepared, and its preferred conformation was analyzed based on its CD spectra: Ac-X1EYSAX2KA-NH2 (11: X1 = ApiC4N3, X2 = Ac6c). The side-chain azido functional group of peptide 11 was efficiently converted to various 1,2,3-triazole groups via Huisgen 1,3-dipolar cycloaddition reactions involving different types of alkynes. The new cyclic dAA derivatives, which combine the advantages of conformational preorganization and side-chain functional groups, should prove to be a useful tool for the further development of biologically active peptides.