Ligation of Side-Chain Unprotected Peptides


A method of chemical ligation of peptides that requires no side chain protecting groups and no activation of the C-.alpha. carboxyl group is presented. The method consists of three steps. In the first step, initiation, a masked glycoaldehyde ester is enzymatically or chemically coupled to the C-terminal carboxylic acid of an sidechain unprotected first peptide. In the second step, ring formation, the masked aldehyde ester of the first peptide is unmasked, and then reacted with the N-.alpha. amino acid of a second sidechain unprotected peptide to form a ring structure. In the third step, rearrangement, the O-acyl ester linkage transfers at higher pH to an N-acyl linkage on the ring to form a peptide bond.



U.S. Patent 5,589,356: Litigation of sidechain unprotected peptides via a masked glycoaldehyde ester and O,N-acyl rearrangement

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Janis Elsner

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James Tam