title: Synthetic procedure for N-Fmoc amino acyl-N-sulfanylethylaniline linker as crypto-peptide thioester precursor with application to native chemical ligation.
abstract: N-sulfanylethylanilide (SEAlide) peptides 1, obtainable using Fmoc-based solid-phase peptide synthesis (Fmoc SPPS), function as crypto-thioesters in native chemical ligation (NCL), yielding a wide variety of peptides/proteins. Their acylating potential with N-terminal cysteinyl peptides 2 can be tuned by the presence or absence of phosphate salts, leading to one-pot/multifragment ligation, operating under kinetically controlled conditions. SEAlide peptides have already been shown to be promising for use in protein synthesis; however, a widely applicable method for the synthesis of N-Fmoc amino acyl-N-sulfanylethylaniline linkers 4, required for the preparation of SEAlide peptides, is unavailable. The present study addresses the development of efficient condensation protocols of 20 naturally occurring amino acid derivatives to the N-sulfanylethylaniline linker 5. N-Fmoc amino acyl aniline linkers 4 of practical use in NCL chemistry, except in the case of the proline- or aspartic acid-containing linker, were successfully synthesized by coupling of POCl(3)- or SOCl(2)-activated Fmoc amino acid derivatives with sodium anilide species 6, without accompanying racemization and loss of side-chain protection. Furthermore, SEAlide peptides 7 possessing various C-terminal amino acids (Gly, His, Phe, Ala, Asn, Ser, Glu, and Val) were shown to be of practical use in NCL chemistry.
authors: Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan.
authors: Ken
authors: K
authors: Sakamoto
authors: Kohei
authors: K
authors: Sato
authors: Akira
authors: A
authors: Shigenaga
authors: Kohei
authors: K
authors: Tsuji
authors: Shugo
authors: S
authors: Tsuda
authors: Hajime
authors: H
authors: Hibino
authors: Yuji
authors: Y
authors: Nishiuchi
authors: Akira
authors: A
authors: Otaka
mesh_terms: D000215:Acylation; D000596:Amino Acids / Q000737:chemistry*; D000813:Anilides / Q000138:chemical synthesis*; D004952:Esters; D005449:Fluorenes / Q000737:chemistry*; D007700:Kinetics; D010455:Peptides / Q000138:chemical synthesis*; D010710:Phosphates / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013457:Sulfur Compounds / Q000138:chemical synthesis*
chemical_list: D000596:Amino Acids; D000813:Anilides; D004952:Esters; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D010710:Phosphates; D013438:Sulfhydryl Compounds; D013457:Sulfur Compounds