Lipid modification of proteins through sortase-catalyzed transpeptidation

J Am Chem Soc. 2008 Dec 3;130(48):16338-43. doi: 10.1021/ja806779e.


A general chemoenzymatic method for the site-specific attachment of lipids to protein substrates is described. Sortase A is used to append short lipid-modified oligoglycine peptides to the C terminus of protein substrates bearing a five amino acid sortase A recognition sequence (LPETG). We demonstrate the attachment of a range of hydrophobic modifications in excellent yield (60-90%), including a simple step for removing the sortase enzyme postreaction. Lipoproteins prepared using these procedures were subsequently shown to associate with mammalian cells in a lipid tail-dependent fashion and localized to the plasma membrane and endosomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacyltransferases / chemistry*
  • Aminoacyltransferases / metabolism*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Catalysis
  • Cell Line, Tumor
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism*
  • Glycine / chemistry
  • Glycine / metabolism
  • Humans
  • Lipid Metabolism*
  • Lipids / chemistry*
  • Molecular Structure
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Substrate Specificity


  • Bacterial Proteins
  • Lipids
  • Peptides
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases
  • Glycine