Open AccessOne-Pot Cyclization and Cleavage of Peptides with N-Terminal Cysteine via the N,S-Acyl Shift of the N-2-[Thioethyl]glycine Residue
Author(s) -
Magdalena Wierzbicka,
Mateusz Waliczek,
Anna Dziadecka,
Piotr Stefanowicz
Publication year - 2021
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.1c01045
Subject(s) - chemistry , tetrapeptide , cysteine , peptide , native chemical ligation , stereochemistry , cleavage (geology) , glycine , cyclic peptide , residue (chemistry) , semisynthesis , bicyclic molecule , epimer , combinatorial chemistry , amino acid , biochemistry , enzyme , geotechnical engineering , fracture (geology) , engineering
We developed a one-pot method for peptide cleavage from a solid support via the N,S -acyl shift of N -2-[thioethyl]glycine and transthioesterification using external thiols to produce cyclic peptides through native chemical self-ligation with the N -terminal cysteine. The feasibility of this methodology is validated by the syntheses of model short peptides, including a tetrapeptide, the bicyclic sunflower trypsin inhibitor SFTI-1, and rhesus Θ-defensin RTD-1. Synthesis of the whole peptide precursor can be fully automated and proceeds without epimerization or dimerization.