AstraZeneca, Alderley Park, Macclesfield, Cheshire SK104TG, England, United Kingdom.
Bioorg Med Chem. 2010 Nov 1;18(21):7486-96. doi: 10.1016/j.bmc.2010.08.052. Epub 2010 Sep 24.
The displacement of probes that bind selectively to subdomains IIA or IIIA on human serum albumin (HSA) by competing compounds has been followed using fluorescence spectroscopy, and has therefore been used to assign a primary binding site for these compounds in the presence and absence of fatty acids. The crystal structures have also been solved for three compounds: a matched pair of carboxylic acids whose binding strength to HSA unexpectedly decreased as the lipophilicity increased; and a highly bound sulphonamide that appeared not to displace the probes in the displacement assay. The crystallography results support the findings from the fluorescence displacement assay. The results indicate that drug binding to subdomain IB might also be important location for certain compounds.
使用荧光光谱法跟踪了选择性结合人血清白蛋白 (HSA) 亚域 IIA 或 IIIA 的探针被竞争化合物取代的情况，因此，在存在和不存在脂肪酸的情况下，该方法被用于确定这些化合物的主要结合位点。还解决了三种化合物的晶体结构：一对匹配的羧酸，其与 HSA 的结合强度出人意料地随着亲脂性的增加而降低；以及一种高度结合的磺酰胺，在置换测定中似乎没有置换探针。晶体学结果支持荧光置换测定的结果。结果表明，某些化合物与亚域 IB 的药物结合也可能是一个重要位置。
