Native chemical ligation through in situ O to S acyl shift.
[reaction: see text] A novel strategy to generate thioester peptides compatible with Fmoc chemistry is presented. Peptide-C(alpha)oxy-(2-mercapto-1-carboxyamide)ethyl ester undergoes an O to S acyl shift during ligation and the newly formed thioester intermediate reacts with an N-terminal cysteine fragment generating a product with native amide bond at the ligation site.
Botti
Paolo
P
Geneprot Inc., Geneva Branch, 2, Pre-de-la Fontaine, 1217 Meyrin, Switzerland. paolo.botti@geneprot.com
Villain
Matteo
M
Manganiello
Sonia
S
Gaertner
Hubert
H
D000577:Amides / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012680:Sensitivity and Specificity; D013455:Sulfur / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis* / Q000737:chemistry; D013997:Time Factors
D000577:Amides; D008024:Ligands; D010455:Peptides; D013463:Sulfuric Acid Esters; D013455:Sulfur; D003545:Cysteine; D010100:Oxygen