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Updated: May 8, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Stereochemistry rules: a single stereocenter changes the conformation of a cyclic tetrapeptide
Fee Li1, Kenny Bravo-Rodriguez, Miguel Fernandez-Oliva
1Lehrstuhl für Organische Chemie II, Ruhr-Universität Bochum , D-44801 Bochum, Germany.
Abstract:
Two novel cyclo(Boc-Cys-Pro-Leu-Cys-OMe) peptides 1 and 2 containing the enantiomeric amino acids d-Leu and l-Leu, respectively, were synthesized to investigate the effect of chiral centers on peptide conformations. By combining a variety of experimental techniques (X-ray crystallography, 2D NMR spectroscopy, temperature-dependent (1)H NMR and IR spectroscopy, and UV-CD spectroscopy) with replica exchange molecular dynamics (REMD) techniques and quantum mechanics/molecular dynamics (QM/MM) calculations, we establish that the stereochemistry of just one residue can noticeably influence the properties of the whole peptide and rationalize the origins of this effect, with potential implications for the rational design of peptides of chemical and biological relevance.
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