Design and synthesis of biomimetic scaffold based on $\beta$- and mixed $\gamma-/\delta$ - amino acids

Abstract

Part Ⅰ. Cation-$\pi$ interaction, one of the most famous noncanonical noncovalent interactions is used in natural protein folding system. Nevertheless, utilizing cation-$\pi$ interaction to design foldamers has not been reported yet. So, we used cation-$\pi$ interaction to design 14-helical $\beta^3$ -peptides that are stable in aqueous solution. Until recently, only $\beta^3$ -peptide stabilized by salt bridge on one or two helical faces showed 14-helical propensity in water. We compared the helical stability of $\beta^3$ -peptides stabilized by cation-$\pi$ interaction (Trp/Orn) with those stabilized by salt-bridge (Glu/Orn) using spectroscopic methods and confirmed 14-helical structure through NMR study. Our newly designed $\beta^3$ -peptide has overall net positive charge, so it is expected to improve cell permeability for biological applications. Part Ⅱ. We have further modified $\gamma^3$ -PNA monomer, which binds RNA more specifically as well as in an antiparallel fashion. Elongation of base linker led to $\gamma^3$ -hPNA, which differentiate RNA from DNA when partially incorporated. Changing to positively charged backbone ($\gamma^3$ -ANA) and 1,2,3-triazole backbone ($\gamma^3$ -triPhe) also succeeded. Improvement in synthetic efficiency and structural analysis is studying further now.