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De Novo Left‐Handed Synthetic Peptidomimetic Foldamers
Author(s) -
She Fengyu,
Teng Peng,
PegueroTejada Alfredo,
Wang Minghui,
Ma Ning,
Odom Timothy,
Zhou Mi,
Gjonaj Erald,
Wojtas Lukasz,
van der Vaart Arjan,
Cai Jianfeng
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201805184
Subject(s) - peptidomimetic , folding (dsp implementation) , left handed , chemistry , crystallography , hydrogen bond , turn (biochemistry) , crystal structure , homogeneous , stereochemistry , molecule , physics , peptide , biochemistry , optics , organic chemistry , electrical engineering , thermodynamics , engineering
Abstract The development of peptidomimetic helical foldamers with a wide repertoire of functions is of significant interest. Herein, we report the X‐ray crystal structures of a series of homogeneous l ‐sulfono‐γ‐AA foldamers and elucidate their folding conformation at the atomic level. Single‐crystal X‐ray crystallography revealed that this class of oligomers fold into unprecedented dragon‐boat‐shaped and unexpected left‐handed helices, which are stabilized by the 14‐hydrogen‐bonding pattern present in all sequences. These l ‐sulfono‐γ‐AApeptides have a helical pitch of 5.1 Å and exactly four side chains per turn, and the side chains lie perfectly on top of each other along the helical axis. 2D NMR spectroscopy, computational simulations, and CD studies support the folding conformation in solution. Our results provide a structural basis at the atomic level for the design of novel biomimetics with a precise arrangement of functional groups in three dimensions.