Native Chemical Ligation - Historical Context

Historical Context

In 1953, Theodor Wieland and coworkers discovered the chemical foundation for this reaction, when the reaction of valine-thioester and cysteine amino acid in aqueous buffer was shown to yield the dipeptide valine-cysteine. The reaction proceeded through the intermediacy of a thioester containing the sulfur of the cysteine residue. Wieland's work led to the 'active ester' method for making protected peptide segments in conventional solution synthesis in organic solvents.

In the 1990s, Stephen Kent and coworkers at The Scripps Research Institute independently developed "Native Chemical Ligation", the first practical method to ligate large unprotected peptide fragments.

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