On-Resin Peptide Cyclization Using the 3-Amino-4-(Methylamino)Benzoic Acid MeDbz Linker

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

Cyclic peptides are becoming increasingly important in drug discovery due to their specific binding properties, larger surface area compared to small molecules, and their ready and modular synthetic accessibility. In this protocol, we describe an on-resin, cleavage-inducing cyclization methodology for the synthesis of cyclic thiodepsipeptides and cyclic homodetic peptides using the 3-amino-4-(methylamino)benzoic acid (MeDbz) linker. We further describe three post-cyclization one-pot procedures, which include desulfurization, disulfide bond formation, and S-alkylation of cysteine residues.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press
Publication date2022
Pages101-115
ISBN (Print)978-1-0716-1688-8
ISBN (Electronic)978-1-0716-1689-5
DOIs
Publication statusPublished - 2022
SeriesMethods in Molecular Biology
Volume2371
ISSN1064-3745

Bibliographical note

Funding Information:
This work was supported by a LEO Foundation Open Competition Grant (LF-OC-19-000039).

Publisher Copyright:
© 2022, Springer Science+Business Media, LLC, part of Springer Nature.

    Research areas

  • Cyclic peptide, Cysteine modification, Desulfurization, Macrocyclization, Native chemical ligation (NCL), One-pot procedure, Peptide cyclization, Solid-phase peptide synthesis (SPPS), Thiodepsipeptide

ID: 289306847