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天线效应和磷光光谱法寻找牛β-乳球蛋白 A 中药物四环素的位置

Antenna effect and phosphorescence spectra to find the location of drug tetracycline in bovine β-lactoglobulin A.

机构信息

Sri Aurobindo Vidyamandir, Hoogly, Chandannagar, West Bengal, India.

The Department of Chemistry, The Bhawanipur Education Society College, Kolkata, 700020, West Bengal, India.

出版信息

J Biol Inorg Chem. 2018 Aug;23(6):917-927. doi: 10.1007/s00775-018-1591-3. Epub 2018 Jul 13.

Abstract

A ternary system comprising of a Eu(III) complex of the drug Tetracycline hydrochloride (EuTC) bound to bovine β-lactoglobulin variant A (BLGA) in aqueous buffer at physiological pH (pH = 7.4) has been investigated to exploit the enhanced "antenna effect" to locate the bound drug and find the microenvironment of the binding site. Steady-state and time-resolved emission studies at room temperature as well as at 77 K have been carried out to evaluate the binding parameters in the binary system consisting of BLGA and tetracycline hydrochloride (TC). Low-temperature phosphorescence studies at 77 K of pure BLGA confirm Trp 19 to be the emitting residue, while Trp 61 is silent. Enhancement of BLGA phosphorescence emission in the ternary system at 77 K indicates that Trp 19 is very close to Eu(III) in the EuTC complex. The molecular docking results further confirm that TC binds close to Trp 19 in a hydrophobic domain. The results thus obtained can provide guidelines to design and synthesize target-oriented drugs as well as suitable bio-probes.

摘要

三元体系包括在生理 pH 值(pH = 7.4)的水溶液缓冲液中,Eu(III)配合物盐酸四环素(EuTC)与牛β-乳球蛋白变体 A(BLGA)结合,旨在利用增强的“天线效应”定位结合药物并找到结合位点的微环境。在室温及 77 K 下进行稳态和时间分辨发射研究,以评估二元体系中 BLGA 和盐酸四环素(TC)的结合参数。纯 BLGA 在 77 K 下的低温磷光研究证实色氨酸 19 是发光残基,而色氨酸 61 是沉默的。三元体系在 77 K 下 BLGA 磷光发射的增强表明色氨酸 19 非常接近 EuTC 配合物中的 Eu(III)。分子对接结果进一步证实,TC 结合在疏水区中靠近色氨酸 19。因此,所得结果可以为设计和合成靶向药物以及合适的生物探针提供指导。

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