Studies related to the relative thermodynamic stability of C-terminal peptidyl esters of O-hydroxy thiophenol: emergence of a doable strategy for non-cysteine ligation applicable to the chemical synthesis of glycopeptides.
A pathway has been devised, wherein a phenolic ester of a C-terminal peptide is ligated with an N-terminal peptide through two consecutive acyl migrations. In the first transacylation, the C-terminus is transferred from a phenol to a newly liberated ortho-thiol function. Subsequently, the acyl group is transported to a proximal benzylamine through a six-membered transition state.
Chen
Gong
G
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, New York, New York 10021, USA.
Warren
J David
JD
Chen
Jiehao
J
Wu
Bin
B
Wan
Qian
Q
Danishefsky
Samuel J
SJ
D003545:Cysteine / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006020:Glycopeptides / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010636:Phenols / Q000737:chemistry*; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013816:Thermodynamics
D004952:Esters; D006020:Glycopeptides; D010636:Phenols; D013438:Sulfhydryl Compounds; C042983:thiophenol; D003545:Cysteine