Patent ID: 7662914

Claim:
A method of synthesizing a polypeptide by ligation of three or more oligopeptide intermediates, the method comprising the steps of: a) forming a ligation product between an oligopeptide possessing both an N-terminal thiazolidine protected cysteine and a C-terminal thioester, said oligopeptide having the formula: wherein: n is an integer from 2 to 100; R 1 is selected from H, C 1-12 alkyl groups optionally substituted with 1-3 substituents selected from halo, nitro, amino, and amino oxycarbonylamino (H 2 N—O—CH 2 —CO—NH—); R 2 is selected from H, C 1-12 alkyl groups optionally substituted with 1-3 substituents selected from halo, nitro, amino, and amino oxycarbonylamino (H 2 N—O—CH 2 —CO—NH—); R 3 is H or an amino protecting group; and R 4 is alkyl having from 1 to 6 carbon atoms or alkylaryl having from 6 to 8 carbon atoms, —CH 2 —CONH 2 , —CH 2 CH 2 CONH 2 , or —(CH 2 ) k —CO—X aa , wherein k is an integer equal to 1 or 2 and Xaa is an amino acid, and a second oligopeptide possessing an N-terminal cysteine; b) treating the ligation product with a nucleophilic agent under acidic conditions to form a second ligation product having a free N-terminal cysteine; and c) repeating steps a) and b) until the polypeptide is formed.