Synthesis and evaluation of the sunflower derived trypsin inhibitor as a potent inhibitor of the type II transmembrane serine protease, matriptase

We report here the synthesis of a 14-amino acid long bicyclic peptide, previously isolated from sunflower seeds. This peptide, termed sunflower trypsin inhibitor (SFTI-1), is one of the most potent naturally occurring small-molecule trypsin inhibitors. In addition to inhibiting trypsin, the synthetic SFTI-1 is also a very potent inhibitor, with a K i of 0.92 nM, of the recently identified epithelial serine protease, termed ‘matriptase’. We report the synthesis of sunflower derived trypsin inhibitor (SFTI-1), a backbone-cyclized disulfide bridged 14-amino acid peptide. It is a very potent inhibitor of the epithelial cell derived serine protease, termed matriptase ( K i=0.92 nM). Molecular modeling provides a good rationale for its inhibitory action.