Work

NCα‐gem‐dimethylated peptoid side chains: A novel approach for structural control and peptide sequence mimetics

Year: 2019

Type: article

Abstract: The design of linear peptoid oligomers adopting well-defined secondary structures while mimicking defined peptide primary sequences is a major challenge in the context of drug discovery. To this end, chemists have developed cis-inducing peptoid side chains to build robust polyproline type I helices. However, the number of efficient examples remains scarce and chemical diversity accessible through the use of these side chains is limited. Herein, we introduce an array of NCα-gem-dimethylated peptoid residues mimicking proteinogenic amino acids. Submonomer synthesis and block-coupling approaches were explored to access heterooligomers incorporating these novel types of side chains. NMR studies of monomer and trimer models showed that the NCα-gem-dimethylated groups exert complete cis control on the backbone amide conformation. Lastly, a preliminary molecular modeling study gave an insight into the preferred orientation of the substituents of the NCα-gem-dimethyl side chains relative to the peptoid backbone.

Source: Biopolymers

DOI: 10.1002/bip.23273

Authors: Radhe Shyam, Lionel Nauton, Gaetano Angelici, Olivier Roy, Claude Taillefumier, Sophie Faure

Institutions: Centre National de la Recherche Scientifique, Université Clermont Auvergne, Sigma Clermont, Institut de Chimie de Clermont-Ferrand

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Agence Nationale de la Recherche, Ministère de l'Enseignement Supérieur et de la Recherche

Award: Novel peptoid architectures: from structure to biological function