title: A Facile N-Mercaptoethoxyglycinamide (MEGA) Linker Approach to Peptide Thioesterification and Cyclization.
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.
authors.affiliation: Department of Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Patrick M M
authors.initials: PM
authors.lastname: Shelton
authors.affiliation: Department of Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Weller
authors.affiliation: Department of Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Champak
authors.identifier: 0000-0001-5772-4438
authors.initials: C
authors.lastname: Chatterjee
mesh_terms: D003500:Cyclization; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D005942:Gluconates / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D004952:Esters; D005942:Gluconates; D010455:Peptides; D013438:Sulfhydryl Compounds; C060886:N-(2-mercaptoethyl)gluconamide