Tuning Peptide Structure and Function through Fluorobenzene Stapling
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Artikelnummer | e202103788 |
Tidsskrift | Chemistry: A European Journal |
Vol/bind | 28 |
Udgave nummer | 8 |
Antal sider | 7 |
ISSN | 0947-6539 |
DOI | |
Status | Udgivet - 2022 |
ID: 290108167