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Peptide Ligations by Using Aryloxycarbonyl‐ o ‐methylaminoanilides: Chemical Synthesis of Palmitoylated Sonic Hedgehog
Author(s) -
PalàPujadas Judith,
Albericio Fernando,
BlancoCanosa Juan B.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201810712
Subject(s) - native chemical ligation , morphogen , sonic hedgehog , chemistry , thioester , peptide , chemical ligation , combinatorial chemistry , cysteine , chemical synthesis , transmembrane protein , hedgehog signaling pathway , hedgehog , patched , ligation , stereochemistry , biochemistry , receptor , signal transduction , in vitro , microbiology and biotechnology , biology , gene , enzyme
A simple procedure for C‐terminal activation of peptides in solution and its application in native chemical ligation and protein synthesis is described. This method involves a mild thioesterification based on the conversion of an aryloxy‐ o ‐methylaminoanilide to thioester under aqueous conditions and in situ ligation with an N‐terminal cysteine peptide. The versatility is shown in pH‐controlled sequential ligations. To illustrate the usefulness of this methodology, we synthesized the palmitoylated N‐terminal domain of human Sonic Hedgehog, a morphogen protein that binds the transmembrane receptor Patched and activates the Hedgehog signaling pathway, involved in embryonic development and in the proliferation of multiple tumors. This approach extends the chemical toolset of chemical protein synthesis based on o ‐aminoanilide and o ‐methylaminoanilide peptides.