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Tuning Peptide Structure and Function through Fluorobenzene Stapling.
- Source :
-
Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2022 Feb 07; Vol. 28 (8), pp. e202103788. Date of Electronic Publication: 2022 Jan 12. - Publication Year :
- 2022
-
Abstract
- Cyclic peptides are promising next-generation therapeutics with improved biological stability and activity. A catalyst-free stapling method for cysteine-containing peptides has been developed that enables fine-tuning of the macrocycle by using the appropriate regioisomers of fluorobenzene linkers. Stapling was performed on the unprotected linear peptide or, more conveniently, directly on-resin after peptide synthesis. NMR spectroscopy and circular dichroism studies demonstrate that the type of stapling can tune the secondary structures of the peptides. The method was applied to a set of potential agonists for melanocortin receptors, generating a library of macrocyclic potent ligands with ortho, meta or para relationships between the thioethers. Their small but significant differences in potency and efficacy demonstrate how the method allows facile fine-tuning of macrocyclic peptides towards biological targets from the same linear precursor.<br /> (© 2021 Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1521-3765
- Volume :
- 28
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Chemistry (Weinheim an der Bergstrasse, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 34897848
- Full Text :
- https://doi.org/10.1002/chem.202103788