Efficient semisynthesis of a tetraphosphorylated analogue of the type I TGFβ receptor

Chemical equation presented Semisynthesis of an active tetraphosphorylated analogue of the Type I TGFβ receptor is reported. An efficient native chemical ligation protocol was developed to link a tetraphosphopeptide and a recombinant receptor fragment. Synthesis of the peptide α-thioester on a 4-sulfamylbutyryl resin was optimized following the characterization of a major side reaction and subsequent substitution of norleucine for methionine in the peptide sequence. These optimized protocols will be applicable to the semisynthesis of related protein kinases.