A Highly Stable Short α-Helix Constrained by a Main-Chain Hydrogen-Bond Surrogate
Abstract
Herein we describe a strategy for the preparation of artificial alpha-helices involving replacement of one of the main-chain hydrogen bonds with a covalent linkage. To mimic the C=O...H-N hydrogen bond as closely as possible, we envisioned a covalent bond of the type C=X-Y-N, where X and Y are two carbon atoms connected through an olefin metathesis reaction. Our results demonstrate that the replacement of a hydrogen bond between the i and i + 4 residues at the N-terminus of a short peptide with a carbon-carbon bond results in a highly stable constrained alpha-helix at physiological conditions as indicated by CD and NMR spectroscopies. The advantage of this strategy is that it allows access to short alpha-helices with strict preservation of molecular recognition surfaces required for biomolecular interactions.
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Self-citation
- Authors
- Chapman, R. N., Dimartino, G., & Arora, P. S.
- Affiliations
- New York University (US)
- ORCID
- Arora, Paramjit S.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2004-09-10
- Volume
- 126
- Issue
- 39
- Pages
- 12252-12253
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2094251756
- Cited by
- 228
- References
- 16
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 6 · 2018: 11 · 2017: 17 · 2016: 19 · 2015: 15 · 2014: 25 · 2013: 11 · 2012: 3
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- olefin metathesis, peptide stability, peptidomimetics
- MeSH terms
- Alanine, Circular Dichroism, Hydrogen Bonding, Peptides, Protein Structure, Secondary, Glutamic Acid, Nuclear Magnetic Resonance, Biomolecular
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