Solid-Phase Synthesis and Circular Dichroism Study of -ABpeptoids

Abstract

The development of peptidomimetic foldamers that can form well-defined folded structures is highly desirable yet challenging. We previously reported on -ABpeptoids, oligomers of N-alkylated (2)-homoalanines and found that due to the presence of chiral methyl groups at -positions, -ABpeptoids were shown to adopt folding conformations. Here, we report -ABpeptoids having chiral methyl group at -positions rather than -positions as a different class of peptoids with backbone chirality. We developed a facile solid-phase synthetic route that enables the synthesis of -ABpeptoid oligomers ranging from 2-mer to 8-mer in excellent yields. These oligomers were shown to adopt ordered folding conformations based on circular dichroism (CD) and NMR studies. Overall, these results suggest that -ABpeptoids represent a novel class of peptidomimetic foldamers that will find a wide range of applications in biomedical and material sciences.