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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| Published in | Journal of the American Chemical Society Vol. 139; no. 11; pp. 3946 - 3949 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
American Chemical Society
22.03.2017
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| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | Shelton, Patrick M. M Chatterjee, Champak Weller, Caroline E |
| AuthorAffiliation | Department of Chemistry University of Washington |
| AuthorAffiliation_xml | – name: Department of Chemistry – name: University of Washington |
| Author_xml | – sequence: 1 givenname: Patrick M. M surname: Shelton fullname: Shelton, Patrick M. M – sequence: 2 givenname: Caroline E surname: Weller fullname: Weller, Caroline E – sequence: 3 givenname: Champak orcidid: 0000-0001-5772-4438 surname: Chatterjee fullname: Chatterjee, Champak email: chatterjee@chem.washington.edu |
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| Copyright | Copyright © 2017 American Chemical Society |
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| DOI | 10.1021/jacs.6b13271 |
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| Title | A Facile N‑Mercaptoethoxyglycinamide (MEGA) Linker Approach to Peptide Thioesterification and Cyclization |
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