Ji Chengjie, Xin Guang, Duan Feixia, Huang Wen, Tan Taichang
Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China.
Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China.
Ann Transl Med. 2020 Feb;8(4):92. doi: 10.21037/atm.2019.12.100.
Novel haloemodin (HEI2) synthesized by modifying emodin, a traditional Chinese medicine component, possesses remarkable antibacterial activity, being much more effective than its parent nucleus, emodin.
Firstly, we discovered that HEI2 increases bacterial cell membrane permeability to potassium ions more drastically than emodin. We thus further investigated the interaction of haloemodin and protein using a fluorescence quenching and circular dichroism (CD) study based on bovine serum albumin (BSA).
HEI2 spontaneously bound to BSA at Trp 212 residue (subdomain IIA) by hydrogen bonds and van der Waals interactions to forms HEI2-BSA complexes, and this binding decreased the α-helical content of BSA. We also confirmed that emodin bound to BSA by hydrophobic interaction alone.
These results suggest that the main responses for the substantial antibacterial activities of HEI2 are a disruption of the bacterial plasma membrane function and the interaction with biological functional proteins. Furthermore, the study of the interaction of drugs with BSA, which has a fluorescent group tryptophan residue similar to many bio-functional proteins, will be a simple and inexpensive scope-reducing method in screening new drugs.
通过修饰中药成分大黄素合成的新型卤代大黄素（HEI2）具有显著的抗菌活性，比其母核大黄素更有效。
首先，我们发现HEI2比大黄素更能显著增加细菌细胞膜对钾离子的通透性。因此，我们基于牛血清白蛋白（BSA），利用荧光猝灭和圆二色性（CD）研究进一步探究卤代大黄素与蛋白质的相互作用。
HEI2通过氢键和范德华相互作用在色氨酸212残基（亚结构域IIA）处自发结合到BSA上，形成HEI2-BSA复合物，这种结合降低了BSA的α-螺旋含量。我们还证实大黄素仅通过疏水相互作用与BSA结合。
这些结果表明，HEI2强大抗菌活性的主要作用是破坏细菌质膜功能以及与生物功能蛋白的相互作用。此外，研究药物与BSA的相互作用，BSA具有与许多生物功能蛋白类似的荧光基团色氨酸残基，将是一种在筛选新药时简单且成本低廉的缩小研究范围的方法。
