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Updated: May 14, 2026

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
Cis-trans amide bond rotamers in β-peptoids and peptoids: evaluation of stereoelectronic effects in backbone and side
Jonas S Laursen1, Jens Engel-Andreasen, Peter Fristrup
1Department of Chemistry, Technical University of Denmark, Kemitorvet 207, DK-2800, Kongens Lyngby, Denmark.
Abstract:
Non-natural peptide analogs have significant potential for the development of new materials and pharmacologically active ligands. One such architecture, the β-peptoids (N-alkyl-β-alanines), has found use in a variety of biologically active compounds but has been sparsely studied with respect to folding propensity. Thus, we here report an investigation of the effect of structural variations on the cis-trans amide bond rotamer equilibria in a selection of monomer model systems. In addition to various side chain effects, which correlated well with previous studies of α-peptoids, we present the synthesis and investigation of cis-trans isomerism in the first examples of peptoids and β-peptoids containing thioamide bonds as well as trifluoroacetylated peptoids and β-peptoids. These systems revealed an increase in the preference for cis-amides as compared to their parent compounds and thus provide novel strategies for affecting the folding of peptoid constructs. By using NMR spectroscopy, X-ray crystallographic analysis, and density functional theory calculations, we present evidence for the presence of thioamide-aromatic interactions through C(sp(2))-H···S(amide) hydrogen bonding, which stabilize certain peptoid conformations.
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