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Stereochemistry Rules: A Single Stereocenter Changes the Conformation of a Cyclic Tetrapeptide

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posted on 19.09.2013, 00:00 by Fee Li, Kenny Bravo-Rodriguez, Miguel Fernandez-Oliva, Juan M. Ramirez-Anguita, Klaus Merz, Manuela Winter, Christian W. Lehmann, Wolfram Sander, Elsa Sanchez-Garcia
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 1H 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.