[논문]Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro

Kim, Ji Hye; Kim, Young Soo; Choi, Jang-Gi; Li, Wei; Lee, Eun Jin; Park, Jin-Wan; Song, Jaeyoung; Chung, Hwan-Suck

doi:10.3390/ijms21093239

[해외논문] Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro 원문보기

International journal of molecular sciences, v.21 no.9, 2020년, pp.3239 -

Kim, Ji Hye (Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea) , Kim, Young Soo (jkim2903@kiom.re.kr (J.H.K.)) , Choi, Jang-Gi (yskim527@kiom.re.kr (Y.S.K.)) , Li, Wei (jang-gichoi@kiom.re.kr (J.-G.C.)) , Lee, Eun Jin (liwei1986@kiom.re.kr (W.L.)) , Park, Jin-Wan (dldmswls0416@naver.com (E.J.L.)) , Song, Jaeyoung (Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea) , Chung, Hwan-Suck (jkim2903@kiom.re.kr (J.H.K.))

Abstract ▼ AI-Helper

Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitory activities on PD-1/PD-L1 protein–protein interaction (PPI), biochemical assays including competitive ELISA and biolayer interferometry (BLI) systems were performed. Cellular PD-1/PD-L1 blocking activity was measured in a co-culture system with PD-1 Jurkat and PD-L1/aAPC CHO-K1 cells by T-cell receptor (TCR) activation-induced nuclear factor of activated T cells (NFAT)-luciferase reporter assay. The detailed binding mode of action was simulated by an in silico docking study and pharmacophore analysis. Competitive ELISA revealed that KO and its glycoside KR significantly inhibited PD-1/PD-L1 interaction. Cellular PD-1/PD-L1 blocking activity was monitored by KO and KR at non-cytotoxic concentration. Surface plasmon resonance (SPR) and biolayer interferometry (BLI) analysis suggested the binding affinity and direct inhibition of KR against PD-1/PD-L1. An in silico docking simulation determined the detailed mode of binding of KR to PD-1/PD-L1. Collectively, these results suggest that KR could be developed as a potent small molecule inhibitor for PD-1/PD-L1 blockade.

Keyword

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