Structure-Activity Relationship Study on Col-003, a Protein-Protein Interaction Inhibitor between Collagen and Hsp47.
This study demonstrates the structure-activity relationship of Col-003, a potent collagen-heat-shock protein 47 (Hsp47) interaction inhibitor. Col-003 analogues were successfully synthesized by Pd(0)-catalyzed cross-coupling reactions of 5-bromosalicylaldehyde derivatives with alkyl-metal species, and the inhibitory activities of the synthetic analogues were evaluated using surface plasmon resonance analysis (BIAcore). We succeeded in discovering two potent inhibitors that showed 85 and 81% inhibition at a concentration of 1.9 µM against the collagen-Hsp47 interaction. This indicates that elongation of an alkyl linker between two aromatic rings could considerably improve inhibitory activity due to the adjustment of a pendant phenyl moiety to an appropriate position, in addition to the hydrophobic interaction with an alkyl linker moiety.
['Yoshida|Masahito|M|', 'Saito|Masazumi|M|', 'Ito|Shinya|S|', 'Ogawa|Koji|K|', 'Goshima|Naoki|N|', 'Nagata|Kazuhiro|K|', 'Doi|Takayuki|T|']
D000447:Aldehydes D000818:Animals D002384:Catalysis D003094:Collagen D050958:HSP47 Heat-Shock Proteins D010165:Palladium D060066:Protein Interaction Maps D054852:Small Molecule Libraries D013329:Structure-Activity Relationship D020349:Surface Plasmon Resonance
collagen heat-shock protein 47 protein–protein interaction small-molecule inhibitor