Helicity control and post-synthetic modification of β-peptide and its analogues

Abstract

Unnatural β-peptides adopt stable secondary structures even at short oligomers, have a wide range of structural diversity, and exhibit remarkable in vivo stability. Based on these properties, β-peptides are well documented as a building block of functional materials. In this context, it is necessary to establish a design strategy for β-peptides. In this dissertation, helicity control of the helical β-peptide and its analogues by transforming each element consisting of the peptide backbone are discussed. Through the substitution of the oxygen atom of the amide with sulfur atoms, precise control of the secondary and higher order structure of β-peptide was achieved. Moreover, post-synthetic modification enables the synthesis of diverse derivatives. Otherwise, a helical α/γ-peptide insensitive toward chiral information was developed, and an intermediate structure in the interconversion between left- and right-handed helices was observed. In addition, enantiopure cyclic β-amino acids comprising various functional groups were successfully synthesized. These findings are expected to improve understanding of the structural properties of a diverse range of unnatural peptides and offer insights for the development of innovative peptide design strategies.