去唾液酸糖蛋白受体
生物信息学
小分子
化学
表面等离子共振
药物发现
组合化学
分子
对接(动物)
体外
药物输送
药品
纳米技术
生物物理学
生物化学
药理学
材料科学
生物
肝细胞
纳米颗粒
医学
有机化学
护理部
基因
作者
Alexander G. Majouga,Yan A. Ivanenkov,Mark S. Veselov,Anton V. Lopukhov,Svetlana Yu. Maklakova,Елена К. Белоглазкина,P. V. Binevski,Natalia L. Klyachko,Yuri Sandulenko,N. S. Galkina,Victor Koteliansky
出处
期刊:Current Drug Delivery
[Bentham Science]
日期:2016-11-08
卷期号:13 (8): 1303-1312
被引量:7
标识
DOI:10.2174/1567201813666160719144651
摘要
During the past decade asialoglycoprotein receptor (ASGP-R) expressed predominantly by hepatocytes has attracted a considerable attention as a convenient biomolecular trap for targeted drug delivery. Currently, several selective galactose-containing ligands equipped by drug molecules, e.g. known anticancer therapeutics, as well as diagnostic tools are under active preclinical development. In this paper, we have carried out a rational in silico screening among the molecules available in ChemDiv collection and compounds provided by our colleagues to reveal potential ASGP-R binders. Thus, 3D molecular docking approach provided a set of 100 `high score` molecules that was subsequently evaluated in vitro using an advanced Surface Plasmon Resonance (SPR) technique. As a result, dozens of novel small-molecule ASGP-R ligands with high diversity in structure were identified. Several hits showed the binding affinity much more better than that determined for galactose and Nacetylgalactosamine which were used as reference compounds. The disclosed molecules can be reasonably regarded as promising molecular devices for targeted drug delivery to hepatocytes. Keywords: Asialoglycoprotein receptor (ASGRP-R), drug delivery, docking, in silico, screening.
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