Long peptide thioesters for accessing to functional ubiquitin-like peptide conjugates

What is it about?

Large proteins can be produced by linking sequentially and site-specifically unprotected peptide segments together by using selective peptide bond forming reactions in water such as the NCL reaction or the SEA native peptide ligation. We describe a simple method to produce large peptide segments which display the appropriate functional groups for building proteins. We illustrate the method by the first total synthesis of a 12 kDa functional small ubiquitin-like modifier (SUMO) peptide conjugate.

Featured Image

Why is it important?

Large peptide thioesters are difficult to produce using the Fmoc solid phase peptide synthesis (SPPS). We describe a solution to this problem. Moreover, we show that the bis(2-sulfanylethyl)amido (SEA) peptide thioester surrogate enables to extend the limits of protein total synthesis by giving a simple and rapid access to small ubiquitin-like modifier (SUMO) peptide conjugates. SUMO is a post-translational modification which plays a crucial role in the regulation of cell the machinery.