Discovery of macrocyclic peptide targeting cMet as advances for neurotherapy

Abstract

cMet belongs to a family tyrosine kinases receptor and is expressed in many cells such as neurocyte and hepatocyte. Upon binding with hepatocyte growth factor (HGF), cMet is activated and the complex promotes cell/tissue regeneration. In this review, we introduce our current research about development of new artificial cytokines (e.g. agonists) for cMet by using a cMet specific binding macrocyclic peptide that was obtained from Random non–standard Peptides Integrated Discovery (RaPID) system. One of the agonists is a peptide–based cytokine and it is an organic synthesizable agonist. The other agonist is a protein–based agonist, named Mirabody, in which the peptide sequence is grafted in the Fc protein. Its activity is almost as potent as the natural ligand HGF, but it has much better pharmacokinetics and thereby potential for the development of cMet–specific super–agonistic drugs.