Patent ID: 7030218

Claim:
A method for synthesizing a desired polypeptide of formula: aa NH 2 -Q-aa x -aa y -W-aa COOH wherein Q and W each denote the optional presence of one or more additional amino acid residues, aa NH 2 denotes the N-terminal amino acid residue of the polypeptide; aa x and aa y denote internal adjacent amino acid residues, having side chains x and y, respectively, and wherein aa y is a non-ribosomally synthesized amino acid residue and aa COOH denotes the C-terminal amino acid residue of the polypeptide; said method comprising: (A) ligating a first peptide having the formula: aa NH 2 -Q-aa x -COSR, wherein R is any group compatible with the thioester group, to a second peptide having the formula: Cys-W-aa COOH to thereby form the polypeptide: aa NH 2 -Q-aa x -Cys-W-aa COOH ; and (B) incubating said polypeptide in the presence of a reagent R aa -X, where R aa is a group whose structure comprises the side chain of amino acid residue aa y ; and X is a good leaving group; said incubation being under conditions sufficient to form said desired polypeptide.