College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
Biomolecules. 2024 Jun 30;14(7):785. doi: 10.3390/biom14070785.
Chemical proteomics using biotin probes of natural products have significantly advanced our understanding of molecular targets and therapeutic potential. This review highlights recent progress in the application of biotin probes of homoisoflavonoids for identifying binding proteins and elucidating mechanisms of action. Notably, homoisoflavonoids exhibit antiangiogenic, anti-inflammatory, and antidiabetic effects. A combination of biotin probes, pull-down assays, mass spectrometry, and molecular modeling has revealed how natural products and their derivatives interact with several proteins such as ferrochelatase (FECH), soluble epoxide hydrolase (sEH), inosine monophosphate dehydrogenase 2 (IMPDH2), phosphodiesterase 4 (PDE4), and deoxyhypusine hydroxylase (DOHH). These target identification approaches pave the way for new therapeutic avenues, especially in the fields of oncology and ophthalmology. Future research aimed at expanding the repertoire of target identification using biotin probes of homoisoflavonoids promises to further elucidate the complex mechanisms and develop new drug candidates.
利用天然产物生物素探针的化学蛋白质组学研究显著促进了我们对分子靶标和治疗潜力的理解。本综述重点介绍了同型异黄酮生物素探针在鉴定结合蛋白和阐明作用机制方面的最新进展。值得注意的是,同型异黄酮具有抗血管生成、抗炎和抗糖尿病作用。生物素探针、下拉测定、质谱和分子建模的组合揭示了天然产物及其衍生物如何与几种蛋白质相互作用,如亚铁螯合酶 (FECH)、可溶性环氧化物水解酶 (sEH)、肌苷单磷酸脱氢酶 2 (IMPDH2)、磷酸二酯酶 4 (PDE4) 和脱氧次黄嘌呤羟化酶 (DOHH)。这些靶标鉴定方法为新的治疗途径铺平了道路,特别是在肿瘤学和眼科学领域。未来旨在扩大同型异黄酮生物素探针靶标鉴定谱的研究有望进一步阐明复杂机制并开发新的候选药物。