A Facile N‑Mercapto­ethoxy­glycinamide (MEGA) Linker Approach to Peptide Thioesterification and Cyclization

The C-terminal electrophilic activation of peptides by α-thioesterification requires strongly acidic conditions or complex chemical manipulations, which ultimately limit functional group compatibility and broad utility. Herein, we report a readily accessible N-mercapto­ethoxy­glycinamide (MEGA) soli...

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Bibliographic Details
Published inJournal of the American Chemical Society Vol. 139; no. 11; pp. 3946 - 3949
Main Authors Shelton, Patrick M. M, Weller, Caroline E, Chatterjee, Champak
Format Journal Article
LanguageEnglish
Published American Chemical Society 22.03.2017
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Summary:The C-terminal electrophilic activation of peptides by α-thioesterification requires strongly acidic conditions or complex chemical manipulations, which ultimately limit functional group compatibility and broad utility. Herein, we report a readily accessible N-mercapto­ethoxy­glycinamide (MEGA) solid-phase linker for the facile synthesis of latent peptide α-thioesters. Incubating peptide-MEGA sequences with 2-mercapto­ethane­sulfonic acid at mildly acidic pH yielded α-thioesters that were directly used in NCL without purification. The MEGA linker yielded robust access to thioesters ranging in length from 4 to 35 amino acids, and greatly simplified the synthesis of cyclic peptides. Finally, the high utility of MEGA was demonstrated by the one-pot synthesis of a functional analog of the Sunflower Trypsin Inhibitor 1.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.6b13271