Abstract
While a range of strategies exist to accomplish peptide macrocyclization, they are frequently limited by the need for orthogonal protection or provide little opportunity for structural diversification. We have evaluated an efficient macrocyclization method that employs nucleophilic aromatic substitution (SNAr) to create thioether macrocycles. This versatile macrocyclization, orthogonal to conventional peptide synthesis, can be performed in solution on unprotected peptidomimetics or on resin-bound peptides with side-chain protection in place. We show that the electron-withdrawing groups present in the products can be further utilized in subsequent orthogonal reactions to alter the peptide properties or to add prosthetic groups. The macrocyclization strategy was applied to the design of melanocortin ligands, generating a library of potent melanocortin agonists that exhibit distinct subtype selectivity.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
