Peptide Ligations by Using Aryloxycarbonyl-o-methylaminoanilides: Chemical Synthesis of Palmitoylated Sonic Hedgehog.
Angew Chem Int Ed Engl
; 57(49): 16120-16125, 2018 12 03.
Article
em En
| MEDLINE
| ID: mdl-30307096
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Proteínas Hedgehog
/
Anilidas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article