title: Total synthesis of biotinylated N domain of human hepatocyte growth factor.
abstract: Hepatocyte growth factor/scatter factor (HGF/SF) is the high affinity ligand of MET tyrosine kinase receptor. We report here the total synthesis of a biotinylated analogue of human HGF/SF N domain. Functionally, N domain is part of the HGF/SF high affinity binding site for MET and also the main HGF/SF binding site for heparin. The 97 Aa linear chain featuring a C-terminal biotin group was assembled in high yield using an N-to-C one-pot three segments assembly strategy relying on a sequential Native Chemical Ligation (NCL)/bis(2-sulfanylethyl)amido (SEA) native peptide ligation process. The folded protein displayed the native disulfide bond pattern and showed the ability to bind heparin.
authors.affiliation: UMR CNRS 8161 Univ Lille Nord de France, Institut Pasteur de Lille, 1 rue du Pr Calmette, Lille 59021, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Raibaut
authors.forename: Jérome
authors.initials: J
authors.lastname: Vicogne
authors.forename: Bérénice
authors.initials: B
authors.lastname: Leclercq
authors.forename: Hervé
authors.initials: H
authors.lastname: Drobecq
authors.forename: Rémi
authors.initials: R
authors.lastname: Desmet
authors.forename: Oleg
authors.initials: O
authors.lastname: Melnyk
mesh_terms: D001710:Biotin / Q000737:chemistry*; D019921:Biotinylation; D017228:Hepatocyte Growth Factor / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D017228:Hepatocyte Growth Factor; D001710:Biotin