The folding propensity of α/sulfono-γ-AA peptidic foldamers with both left- and right-handedness
Open Access
- 10 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Chemistry
- Vol. 4 (1), 1-9
- https://doi.org/10.1038/s42004-021-00496-0
Abstract
The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules. To maximize their application potential through structure-based design, it is imperative to control their helical handedness based on their molecular scaffold. Herein we first demonstrate the generalizability of the solid-state right-handed helical propensity of the 413-helix of L-α/L-sulfono-γ-AA peptides that as short as 11-mer, using the high-resolution X-ray single crystallography. The atomic level folding conformation of the foldamers was also elucidated by 2D NMR and circular dichroism under various conditions. Subsequently, we show that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains, as demonstrated by the left-handed 413-helix comprising 1:1 D-α/D-sulfono-γ-AA peptide. In addition, a heterochiral coiled-coil-like structure was also revealed for the first time, unambiguously supporting the impact of chirality on their helical handedness. Our findings enable the structure-based design of unique folding biopolymers and materials with the exclusive handedness or the racemic form of the foldamers in the future.Keywords
Funding Information
- NSF | BIO | Division of Molecular and Cellular Biosciences (170850)
- U.S. Department of Health & Human Services | NIH | NICHD | National Center for Medical Rehabilitation Research (9R01AI152416-06)
- U.S. Department of Health & Human Services | NIH | NIH Clinical Center (1R01AG056569-01)
This publication has 61 references indexed in Scilit:
- Conformational photoswitching of a synthetic peptide foldamer bound within a phospholipid bilayerScience, 2016
- Foldamers with Heterogeneous BackbonesAccounts of Chemical Research, 2008
- Foldamers as versatile frameworks for the design and evolution of functionNature Chemical Biology, 2007
- Chimeric (α/β + α)-Peptide Ligands for the BH3-Recognition Cleft of Bcl-xL: Critical Role of the Molecular Scaffold in Protein Surface RecognitionJournal of the American Chemical Society, 2005
- Helical β-Peptide Inhibitors of the p53-hDM2 InteractionJournal of the American Chemical Society, 2004
- Helical Peptoid Mimics of Magainin-2 AmideJournal of the American Chemical Society, 2003
- Selective Binding of TAR RNA by a Tat-Derived β-PeptideOrganic Letters, 2003
- Non-haemolytic β-amino-acid oligomersNature, 2000
- De Novo Design of Antibacterial β-PeptidesJournal of the American Chemical Society, 1999
- Synthesis and Biological Evaluation of a Cyclo--tetrapeptide as a Somatostatin AnalogueAngewandte Chemie, 1999