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

The C-terminal electrophilic activation of peptides by alpha-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) so...

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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., Chatterjeee, Champak
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 22.03.2017
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
CYCLIC PEPTIDE
RACEMIZATION
SOLID-PHASE SYNTHESIS
PROTEIN-SYNTHESIS
NATIVE CHEMICAL LIGATION
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Summary:The C-terminal electrophilic activation of peptides by alpha-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 alpha-thioesters. Incubating, peptide-MEGA sequences with 2-mercaptoethanewlfonic, acid at mildly acidic pH yielded alpha-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.
Bibliography:NIH RePORTER
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ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.6b13271