Structure-Activity Relationship Study on Col-003, a Protein-Protein Interaction Inhibitor between Collagen and Hsp47.


Yoshida M(1), Saito M(1), Ito S(2), Ogawa K(3), Goshima N(3), Nagata K(2), Doi T(1)(4).
Author information:
(1)Graduate School of Pharmaceutical Science, Tohoku University.
(2)Institute for Protein Dynamics, Kyoto Sangyo University.
(3)National Institute of Advanced Industrial Science and Technology
(4)Graduate School of Life Sciences, Tohoku University.


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.