2024-03-29T11:26:45Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:02001710
2022-04-27T10:00:49Z
117:7598
3:62:5298:5460
Structure–Activity Relationship Study on Col-003, a Protein–Protein Interaction Inhibitor between Collagen and Hsp47
吉田, 将人
ヨシダ, マサヒト
YOSHIDA, Masahito
Saito, Masazumi
Ito, Shinya
Ogawa, Koji
Goshima, Naoki
Nagata, Kazuhiro
Doi, Takayuki
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.
journal article
Pharmaceutical Society of Japan
日本薬学会
2020-03
application/pdf
Chemical and Pharmaceutical Bulletin
3
68
220
226
0009-2363
AA00602100
https://tsukuba.repo.nii.ac.jp/record/2001710/files/CPB_68-3.pdf
eng
31582590
https://doi.org/10.1248/cpb.c19-00634
© 2020 The Pharmaceutical Society of Japan
open access