using an amide bond as an activated ester for peptide coupling reactions

What is it about?

with the evolution of ligation reactions coupling unprotected peptides together to make proteins, there has been a search for Fmoc compatible methods for making the activated ester. Macmillan and co-workers had shown that cysteine could act as an ester under the right conditions (with relevance to origin of life) the α-methylcysteine accelerates this effect by a combination of gem-dimethyl effect and twisting of the amide backbone. Although slow it works and its' easy to synthesise long peptides by Fmoc on standard resins that can be ligated together. Try it yourself!

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