CyProt

One of the great challenges in the development of small protein drugs is the introduction of modifications which allow an increased the stability of the protein, its half-life in biological fluids, the yield of production and folding. The cyclization of small peptides is well developed, whereas the cyclization of large polypeptides or proteins is still in its infancy, primarily due to the difficulty in producing cyclic polypeptides or proteins using living systems. Given the fast growing importance of long polypeptides or proteins in the drug market, the development of processes enabling the efficient total synthesis of cyclic analogue libraries is of utmost importance. The aim of this project is to develop an innovative self-purifying process enabling the synthesis of large cyclic polypeptides or proteins by performing several sequential ligations of purified and unprotected peptide segments on a water compatible solid support. The method will be automated by adapting a commercially available multiple peptide synthesizer. The technology will be used for optimizing a lead cyclic protein (< 100 amino acids) currently developed in Lille for its capacity to act as a potent mimic of hepatocyte growth factor (HGF), which is the ligand of the MET receptor tyrosine kinase. Such potent MET agonists have a great potential in regenerative medicine. In particular, potent MET agonist can prevent the fulminant hepatic failure, an application which is mainly targeted in this project.