The folding propensity of \u03b1/sulfono-\u03b3-AA peptidic foldamers with both left- and right-handedness

Peng Teng,Yan Shi,Li-June Ming,Wei Jiang,Mengmeng Zheng,Jianfeng Cai,Songyi Xue,Lukasz Wojtas,Mi Zhou,Yong Hu,Darrell Cole Cerrato

doi:10.1038/s42004-021-00496-0

Peng Teng, Yan Shi + Show 9 more

Open Access

https://doi.org/10.1038/s42004-021-00496-0

Copy DOI

Abstract

The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules. To maximize their application potential through structure-based design, it is imperative to control their helical handedness based on their molecular scaffold. Herein we first demonstrate the generalizability of the solid-state right-handed helical propensity of the 413-helix of L-α/L-sulfono-γ-AA peptides that as short as 11-mer, using the high-resolution X-ray single crystallography. The atomic level folding conformation of the foldamers was also elucidated by 2D NMR and circular dichroism under various conditions. Subsequently, we show that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains, as demonstrated by the left-handed 413-helix comprising 1:1 D-α/D-sulfono-γ-AA peptide. In addition, a heterochiral coiled-coil-like structure was also revealed for the first time, unambiguously supporting the impact of chirality on their helical handedness. Our findings enable the structure-based design of unique folding biopolymers and materials with the exclusive handedness or the racemic form of the foldamers in the future.

Highlights

The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules
As the molecular scaffold of α/sulfono-γ-AA peptides is different from α-peptides, which contains 50% of chiral side chains and 50% of achiral sulfonyl side chains, an unambiguous folding structure is needed to support the hypothesis
Our results demonstrated that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains and irrelevant to achiral sulfonyl side chains

Summary

Introduction

The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules To maximize their application potential through structure-based design, it is imperative to control their helical handedness based on their molecular scaffold. 1234567890():,; For decades, the development of synthetic foldamers[1,2] that mimic the structure and function of natural biopolymers has boosted markedly These synthetic oligomers are endowed with enhanced resistance toward proteolytic degradation and sequence diversity, along with promise in biomedical and material applications[2]. 1:1 L-α/L-sulfono-γ-AA hybrid oligomers exhibit a right-handed 13-helix pattern, closely resembling that of α-helix The exploration of this class of foldamer are expected to lead to profound application in functional materials. Our results shed light on the structure-based design of unique folding biopolymers and functional materials with individual handedness or the racemic form of the foldamers

Methods

Results

Conclusion