Synthesis of Lipopeptides by CLipPA Chemistry

Lipidation of polypeptides with a fatty acid to form N-linked lipopeptides can be a time consuming process due to the need to mask other reactive function groups present on the side chains of amino acids. Cysteine Lipidation on a Peptide or Amino acid (CLipPA) technology enables the direct lipidation of unprotected peptides containing a free thiol group to afford S-lipidated lipopeptides. A generalized procedure for the synthesis of S-lipopeptides is described which facilities rapid preparation of tens of analogs of lipopeptides from a single thiolated polypeptide precursor.