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One‐Pot Four‐Segment Ligation Using Seleno‐ and Thioesters: Synthesis of Superoxide Dismutase
Author(s) -
Takei Toshiki,
Andoh Tomoshige,
Takao Toshifumi,
Hojo Hironobu
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201709418
Subject(s) - thioester , chemistry , peptide , superoxide dismutase , chemical ligation , peptide synthesis , native chemical ligation , ligation , combinatorial chemistry , aryl , amino acid , cysteine , biochemistry , enzyme , organic chemistry , microbiology and biotechnology , biology , alkyl
The synthesis of a peptide selenoester was efficiently carried out by the 9‐fluorenylmethoxycarbonyl (Fmoc) method using N‐alkylcysteine, at the C‐terminus of the peptide, as the N‐to‐S acyl shift device. The selenoester selectively reacted with the terminal amino group of the peptide aryl thioester in the presence of N , N ‐diisopropylethylamine and dipyridyldisulfide, thus leaving the aryl thioester intact. Combined with silver‐ion‐promoted and silver‐ion‐free thioester activation methods, a one‐pot four‐segment ligation was realized. The method was successfully used to assemble the entire sequence of superoxide dismutase (SOD), which is composed of 153 amino‐acid residues, in one pot. After the folding reaction, the fully active SOD was obtained.