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NC α‐ gem ‐dimethylated peptoid side chains: A novel approach for structural control and peptide sequence mimetics
Author(s) -
Shyam Radhe,
Nauton Lionel,
Angelici Gaetano,
Roy Olivier,
Taillefumier Claude,
Faure Sophie
Publication year - 2019
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23273
Subject(s) - peptoid , chemistry , side chain , context (archaeology) , stereochemistry , trimer , peptide , combinatorial chemistry , peptidomimetic , amide , sequence (biology) , monomer , organic chemistry , biochemistry , paleontology , dimer , biology , polymer
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 NC α‐ 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 NC α‐ 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 NC α‐ gem ‐dimethyl side chains relative to the peptoid backbone.