Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 50, Pages 26314-26319Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202106794
Keywords
anisotropic; NMR spectroscopy; peptides; poly-4-acrylomorpholine; residual dipolar coupling
Categories
Funding
- Pfizer, Inc.
- NSF [CHE-0130903, CHE-1039870, CHE-1726525]
Ask authors/readers for more resources
This study presents a novel gel for aligning small organic molecules and cyclic peptides in water, which has been proven effective in molecular conformation analysis. The identification of minor conformers that cannot be easily determined by conventional methods will facilitate the use of RDC experiments in structure-based drug design.
Determination of the solution conformation of both small organic molecules and peptides in water remains a substantial hurdle in using NMR solution conformations to guide drug design due to the lack of easy to use alignment media. Herein we report the design of a flexible compressible chemically cross-linked poly-4-acrylomorpholine gel that can be used for the alignment of both small molecules and cyclic peptides in water. To test the new gel, residual dipolar couplings (RDCs) and J-coupling constants were used in the configurational analysis of strychnine hydrochloride, a molecule that has been studied extensively in organic solvents as well as a small cyclic peptide that is known to form an alpha-helix in water. The conformational ensembles for each molecule with the best fit to the data are reported. Identification of minor conformers in water that cannot easily be determined by conventional NOE measurements will facilitate the use of RDC experiments in structure-based drug design.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available