Structure-activity relationship study on col-003, a protein-protein interaction inhibitor between collagen and Hsp47

Masahito Yoshida, Masazumi Saito, Shinya Ito, Koji Ogawa, Naoki Goshima, Kazuhiro Nagata, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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 1.9µM 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.

Original languageEnglish
Pages (from-to)220-226
Number of pages7
JournalChemical and Pharmaceutical Bulletin
Volume68
Issue number3
DOIs
Publication statusPublished - 2020 Mar 1

Keywords

  • Collagen
  • Heat-shock protein 47
  • Protein-protein interaction
  • Small-molecule inhibitor

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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