Tuning Peptide Structure and Function through Fluorobenzene Stapling
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Article number | e202103788 |
Journal | Chemistry: A European Journal |
Volume | 28 |
Issue number | 8 |
Number of pages | 7 |
ISSN | 0947-6539 |
DOIs | |
Publication status | Published - 2022 |
ID: 290108167