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Cys-Cys and Cys-Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents.

ABSTRACT: Easy access to a wide range of structurally diverse stapled peptides is crucial for the development of inhibitors of protein-protein interactions. Herein, we report bis-functional hypervalent iodine reagents for two-component cysteine-cysteine and cysteine-lysine stapling yielding structurally diverse thioalkyne linkers. This stapling method works with unprotected natural amino acid residues and does not require pre-functionalization or metal catalysis. The products are stable to purification and isolation. Post-stapling modification can be accessed via amidation of an activated ester, or via cycloaddition onto the formed thioalkyne group. Increased helicity and binding affinity to MDM2 was obtained for a i,i+7 stapled peptide.

SUBMITTER: Ceballos J

PROVIDER: S-EPMC8048981 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Cys-Cys and Cys-Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents.

Ceballos Javier J Grinhagena Elija E Sangouard Gontran G Heinis Christian C Waser Jerome J

Angewandte Chemie (International ed. in English) 20210308 16

Easy access to a wide range of structurally diverse stapled peptides is crucial for the development of inhibitors of protein-protein interactions. Herein, we report bis-functional hypervalent iodine reagents for two-component cysteine-cysteine and cysteine-lysine stapling yielding structurally diverse thioalkyne linkers. This stapling method works with unprotected natural amino acid residues and does not require pre-functionalization or metal catalysis. The products are stable to purification an ...[more]

PMID: 33450121

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