Fmoc chemistry compatible thio-ligation assembly of proteins

We describe, and compare, two methods which enable the assembly of proteins from peptide thioester fragments prepared by Fmoc chemistry mediated solid phase synthesis. The first, which utilizes iso-thiouronium salts, allows formation of thiophenyl esters directly from partially protected peptides, either in solution or on resin. The second uses `sulfonamide' based safety-catch resins. Data on yields, generality and potential for side-reactions are provided.