A New Protein–Ligand Trapping System to Rapidly Screen and Discover Small-Molecule Inhibitors of PD-L1 from Natural Products DOI Creative Commons

Yazhuo Huang,

Senfeng Sun,

Runxin Yin

и другие.

Molecules, Год журнала: 2025, Номер 30(8), С. 1754 - 1754

Опубликована: Апрель 14, 2025

Chinese herbal medicines have played a significant role in the development of new and effective drugs, but how to identify active ingredients from complex extracts traditional was research difficulty. In recent years, few studies focused on high-efficiency identification small-molecule inhibitors Programmed Death Ligand 1 with lower antigenicity flexible structure tunability. order small molecule PD-L1 extracts, this study established protein–ligand trapping system based high-performance liquid chromatography coupled photo-diode array detector, ion trap/quadrupole time-of-flight tandem mass spectrometry, affinity unit (ACPD-L1-HPLC-PDA-IT-TOF (Q-TOF)-MS) rapidly screen Toddalia asiatica (L.) Lam. Fourteen components were then identified as binders, surface plasmon resonance (SPR) validation results showed that six them—magnoflorine (6), nitidine (22), chelerythrine (24), jatrorrhizine (13), toddaculin (68), toddanol (45)—displayed binding activity. Laser scanning confocal microscopy demonstrated these compounds effectively inhibited PD-1 dose-dependent manner. Additionally, flow cytometry analysis indicated they could promote human lung cancer cell line (A549) apoptosis when co-cultured Peripheral Blood Mononuclear Cells (PBMCs). The system’s innovation lies its first integration dynamic multi-dimensional validation, high-throughput screening capacity for structurally diverse natural products. This workflow overcomes phytochemical bottlenecks by preserving native protein conformations during capture while maintaining chromatographic resolution, offering transformative template accelerating product-derived immunotherapeutics through PD-1/PD-L1 pathway.

Язык: Английский

A New Protein–Ligand Trapping System to Rapidly Screen and Discover Small-Molecule Inhibitors of PD-L1 from Natural Products DOI Creative Commons

Yazhuo Huang,

Senfeng Sun,

Runxin Yin

и другие.

Molecules, Год журнала: 2025, Номер 30(8), С. 1754 - 1754

Опубликована: Апрель 14, 2025

Chinese herbal medicines have played a significant role in the development of new and effective drugs, but how to identify active ingredients from complex extracts traditional was research difficulty. In recent years, few studies focused on high-efficiency identification small-molecule inhibitors Programmed Death Ligand 1 with lower antigenicity flexible structure tunability. order small molecule PD-L1 extracts, this study established protein–ligand trapping system based high-performance liquid chromatography coupled photo-diode array detector, ion trap/quadrupole time-of-flight tandem mass spectrometry, affinity unit (ACPD-L1-HPLC-PDA-IT-TOF (Q-TOF)-MS) rapidly screen Toddalia asiatica (L.) Lam. Fourteen components were then identified as binders, surface plasmon resonance (SPR) validation results showed that six them—magnoflorine (6), nitidine (22), chelerythrine (24), jatrorrhizine (13), toddaculin (68), toddanol (45)—displayed binding activity. Laser scanning confocal microscopy demonstrated these compounds effectively inhibited PD-1 dose-dependent manner. Additionally, flow cytometry analysis indicated they could promote human lung cancer cell line (A549) apoptosis when co-cultured Peripheral Blood Mononuclear Cells (PBMCs). The system’s innovation lies its first integration dynamic multi-dimensional validation, high-throughput screening capacity for structurally diverse natural products. This workflow overcomes phytochemical bottlenecks by preserving native protein conformations during capture while maintaining chromatographic resolution, offering transformative template accelerating product-derived immunotherapeutics through PD-1/PD-L1 pathway.

Язык: Английский

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