Protein chemical synthesis by serine and threonine ligation

Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6657-62. doi: 10.1073/pnas.1221012110. Epub 2013 Apr 8.

Abstract

An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides--ovine-corticoliberin and Forteo--and the human erythrocyte acylphosphatase protein (∼11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc-solid-phase peptide synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / chemical synthesis*
  • Acylphosphatase
  • Aldehydes / chemistry*
  • Animals
  • Chromatography, High Pressure Liquid
  • Corticotropin-Releasing Hormone / chemical synthesis*
  • Humans
  • Mass Spectrometry
  • Molecular Structure
  • Peptides / chemistry*
  • Protein Engineering / methods*
  • Serine / chemistry
  • Sheep
  • Teriparatide / chemical synthesis*
  • Threonine / chemistry

Substances

  • Aldehydes
  • Peptides
  • Teriparatide
  • salicylaldehyde
  • Threonine
  • Serine
  • Corticotropin-Releasing Hormone
  • Acid Anhydride Hydrolases