Native chemical ligation through in situ O to S acyl shift

Org Lett. 2004 Dec 23;6(26):4861-4. doi: 10.1021/ol0481028.

Abstract

[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.

MeSH terms

  • Amides / chemistry
  • Chromatography, High Pressure Liquid
  • Cysteine / chemistry
  • Hydrogen-Ion Concentration
  • Ligands
  • Molecular Structure
  • Oxygen / chemistry*
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Sensitivity and Specificity
  • Sulfur / chemistry*
  • Sulfuric Acid Esters / chemical synthesis*
  • Sulfuric Acid Esters / chemistry
  • Time Factors

Substances

  • Amides
  • Ligands
  • Peptides
  • Sulfuric Acid Esters
  • Sulfur
  • Cysteine
  • Oxygen