Solid phase protein synthesis by sequential ligation of peptide segments

What is it about?

We describe a method to produce large peptides or proteins by coupling sequentially on a water solid phase deprotected peptide segments. This method is chemoselective and is based on SEA chemistry (SEA = bis(2-sulfanylethyl)amido) which constitute a powerful latent thioester. Up to five peptide segments could be ligated to produce a 15 kD polypeptide in excellent purity.

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Why is it important?

The reports describing the solid phase synthesis of proteins are rare, the last one working in the N-to-C direction was published in 1999, highlighting the significance of this work. This method has the potential to be automated and we believe that it will extent considerably the actual limits of protein chemical synthesis.