Solid-Phase Synthesis and Circular Dichroism Study of β-ABpeptoids.

Ganesh A Sable,Kang Ju Lee,Hyun-Suk Lim

doi:10.3390/molecules24010178

Ganesh A Sable, Kang Ju Lee + Show 1 more

Open Access

https://doi.org/10.3390/molecules24010178

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Abstract

The development of peptidomimetic foldamers that can form well-defined folded structures is highly desirable yet challenging. We previously reported on α-ABpeptoids, oligomers of N-alkylated β2-homoalanines and found that due to the presence of chiral methyl groups at α-positions, α-ABpeptoids were shown to adopt folding conformations. Here, we report β-ABpeptoids having chiral methyl group at β-positions rather than α-positions as a different class of peptoids with backbone chirality. We developed a facile solid-phase synthetic route that enables the synthesis of β-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 β-ABpeptoids represent a novel class of peptidomimetic foldamers that will find a wide range of applications in biomedical and material sciences.

Highlights

Peptidomimetic foldamers are a class of artificial oligomers that can form defined and predictable structures that are capable of mimicking the three-dimensional structure and function of natural peptides and proteins [1,2]
As demonstrated in α-ABpeptoids, we envisioned that the introduction of chiral methyl groups at the backbone β-positions would influence the structural conformation of peptoids
We prepared β3 -homoalanines substituted with benzyl or naphthyl group as monomer building blocks because it is known that aromatic side chains such as N-benzyl and N-naphthyl groups in peptoids with chiral side chains play a critical role in forming ordered structures (Scheme 1) [41,42,43,44,45]. (R)-methyl

Summary

Introduction

Peptidomimetic foldamers are a class of artificial oligomers that can form defined and predictable structures that are capable of mimicking the three-dimensional structure and function of natural peptides and proteins [1,2]. Given their improved proteolytic stability and structural diversity compared to native peptides, synthetic peptidomimetic foldamers that adopt well-defined protein secondary structures can be highly useful in biological applications and material sciences [3]. Peptoids possess many of the desirable features of peptidomimetics, they are structurally flexible and generally do not form folding structures because of the lack of amide protons and chirality in their backbones. It has been proven that the introduction of chiral centers to peptoid frameworks enables them to have ordered folding structures, which is in contrast to regular peptoids

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