Naoya Kawakami

Jul 14, 2023 | pericles.pericles-prod.literatumonline.com | Hiroki Sato |Naohiro Terasaka |Kunio Matsumoto |Naoya Kawakami

Abstract Receptor tyrosine kinases (RTKs) are generally activated through their dimerization and/or oligomerization induced by their cognate ligands, and one such RTK hepatocyte growth factor (HGF) receptor, known as MET, plays an important role in tissue regeneration. Here we show the development of ubiquitin (Ub)-based protein ligand multimers, referred to as U-bodies, which act as surrogate agonists for MET, derived from MET-binding macrocyclic peptides.

Jul 14, 2023 | onlinelibrary.wiley.com | Naoya Kawakami |Hiroki Sato |Naohiro Terasaka |Kunio Matsumoto

Results and Discussion First, we investigated the availability of each loop position within Ub for LG using the pharmacophore sequence of aMD4. Six types of aMD4-grafted Ubs were expressed in Escherichia coli, where two consecutive residues within one of the six loop positions were replaced with the pharmacophore sequence of aMD4 flanked by a single Gly as a grafting spacer (Figure S2).