Development of flavonoid probes and the binding mode of the target protein and quercetin derivatives

Ayaka Tsuchiya; Miho Kobayashi; Yuji O Kamatari; Tohru Mitsunaga; Kosei Yamauchi

doi:10.1016/j.bmc.2022.116854

Development of flavonoid probes and the binding mode of the target protein and quercetin derivatives

Bioorg Med Chem. 2022 Aug 15:68:116854. doi: 10.1016/j.bmc.2022.116854. Epub 2022 May 26.

Authors

Ayaka Tsuchiya¹, Miho Kobayashi², Yuji O Kamatari³, Tohru Mitsunaga⁴, Kosei Yamauchi⁵

Affiliations

¹ United Graduate School of Agricultural Science, Gifu University, Gifu, Gifu 501-1193, Japan.
² Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Gifu 501-1193, Japan; Life Science Research Center, Gifu University, Gifu, Gifu 501-1193, Japan.
³ Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Gifu 501-1193, Japan; Life Science Research Center, Gifu University, Gifu, Gifu 501-1193, Japan; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Gifu 501-1193, Japan.
⁴ Faculty of Applied Biological Sciences, Gifu University, Gifu, Gifu 501-1193, Japan.
⁵ Faculty of Applied Biological Sciences, Gifu University, Gifu, Gifu 501-1193, Japan. Electronic address: kosei_y@gifu-u.ac.jp.

PMID: 35667156
DOI: 10.1016/j.bmc.2022.116854

Abstract

This study investigated the mechanism underlying anti-cancer cell migration activity of quercetin derivatives by investigating the binding mode of the target protein. Five flavonoid probes were newly synthesized, and pull down assay using synthesized flavonoid probes indicated matrix metalloproteinase-1 (MMP-1) as the target protein of quercetin derivatives. Quercetin and 3-O-methylquercetin (3MQ) inhibited MMP-1. SPR analysis demonstrated dose dependent interaction between quercetin derivatives and recombinant MMP-1 catalytic domain. And ¹H-¹⁵N heteronuclear single quantum coherence (HSQC) NMR analysis using ¹⁵N-labeled MMP-1 catalytic domain indicated that 3MQ interacted around metal ions in the MMP-1. The development of flavonoid probes can broaden the possibility to discover the new target proteins and elucidate the core mechanisms of the multi bioactivity of flavonoids.

Keywords: Flavonoids; Matrixmetalloproteinase; NMR; Pulldown assay.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Flavonoids* / pharmacology
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Quercetin* / chemistry
Quercetin* / pharmacology

Substances

Flavonoids
Quercetin
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Matrix Metalloproteinase 1