title: One-pot/sequential native chemical ligation using N-sulfanylethylanilide peptide.
abstract: N-Sulfanylethylanilide (SEAlide) peptides were developed with the aim of achieving facile synthesis of peptide thioesters by 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis (Fmoc SPPS). Initially, SEAlide peptides were found to be converted to the corresponding peptide thioesters under acidic conditions. However, the SEAlide moiety was proved to function as a thioester in the presence of phosphate salts and to participate in native chemical ligation (NCL) with N-terminal cysteinyl peptides, and this has served as a powerful protein synthesis methodology. The reactivity of a SEAlide peptide (anilide vs. thioester) can be easily tuned with or without the use of phosphate salts. This interesting property of SEAlide peptides allows sequential three-fragment or unprecedented four-fragment ligation for efficient one-pot peptide/protein synthesis. Furthermore, dual-kinetically controlled ligation, which enables three peptide fragments simultaneously present in the reaction to be ligated in the correct order, was first achieved using a SEAlide peptide. Beyond our initial expectations, SEAlide peptides have served in protein chemistry fields as very useful crypto-peptide thioesters.
authors.affiliation: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan. aotaka@tokushima-u.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Sato
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.forename: Akira
authors.initials: A
authors.lastname: Shigenaga
mesh_terms: D003545:Cysteine / Q000737:chemistry; D004952:Esters; D023303:Oxazolidinones / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D004952:Esters; D023303:Oxazolidinones; D010455:Peptides; D013438:Sulfhydryl Compounds; D003545:Cysteine