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Reversible stapling of unprotected peptides via chemoselective methionine bis-alkylation/dealkylation.

ABSTRACT: We have developed a general peptide macrocyclization strategy that involves a facile and chemoselective methionine bis-alkylation/dealkylation process. This method provides a straightforward and easy approach to generate cyclic peptides with tolerances of all amino acids (including Cys), variable loop sizes, and different linkers. The Met bis-alkylation we apply in this strategy yields two additional on-tether positive charges that could assist in the cellular uptake of the peptides. Notably, the bis-alkylated peptide could be reduced to release the original peptide both in vitro and within cellular environments. This strategy provides an intriguing and facile traceless post-peptide-synthesis modification with enhanced cellular uptakes. Peptides constructed with this method could be utilized to zero in on various protein targets or to achieve other goals, such as drug delivery.

SUBMITTER: Shi X

PROVIDER: S-EPMC5931191 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Reversible stapling of unprotected peptides <i>via</i> chemoselective methionine bis-alkylation/dealkylation.

Shi Xiaodong X Zhao Rongtong R Jiang Yixiang Y Zhao Hui H Tian Yuan Y Jiang Yanhong Y Li Jingxu J Qin Weirong W Yin Feng F Li Zigang Z

Chemical science 20180226 12

We have developed a general peptide macrocyclization strategy that involves a facile and chemoselective methionine bis-alkylation/dealkylation process. This method provides a straightforward and easy approach to generate cyclic peptides with tolerances of all amino acids (including Cys), variable loop sizes, and different linkers. The Met bis-alkylation we apply in this strategy yields two additional on-tether positive charges that could assist in the cellular uptake of the peptides. Notably, th ...[more]

PMID: 29844896

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