Noctor T A, Wainer I W, Hage D S
Department of Oncology, McGill University, Montreal, PQ, Canada.
J Chromatogr. 1992 Jun 10;577(2):305-15. doi: 10.1016/0378-4347(92)80252-l.
A chiral stationary phase for high-performance liquid chromatography, based upon immobilized human serum albumin (HSA), was used to investigate the effect of octanoic acid on the simultaneous binding of a series of drugs to albumin. Octanoic acid was found to bind with high affinity to a primary binding site, which in turn induced an allosteric change in the region of drug binding Site II, resulting in the displacement of compounds binding there. Approximately 80% of the binding of suprofen and ketoprofen to HSA was accounted for by binding at Site II. Octanoic acid was found to also bind to a secondary site on HSA, with much lower affinity. This secondary site appeared to be the warfarin-azapropazone binding area (drug binding Site I), as both warfarin and phenylbutazone were displaced in a competitive manner by high levels of octanoic acid. The enantioselective binding to HSA exhibited by warfarin, suprofen and ketoprofen was found to be due to differential binding of the enantiomers at Site I; the primary binding site for suprofen and ketoprofen was not enantioselective.
一种基于固定化人血清白蛋白（HSA）的高效液相色谱手性固定相，用于研究辛酸对一系列药物与白蛋白同时结合的影响。发现辛酸与一个主要结合位点具有高亲和力，这反过来又在药物结合位点II区域诱导了变构变化，导致结合在那里的化合物被置换。舒洛芬和酮洛芬与HSA的结合中约80%是通过在位点II的结合来解释的。发现辛酸也与HSA上的一个次要位点结合，亲和力要低得多。这个次要位点似乎是华法林 - 阿扎丙宗结合区域（药物结合位点I），因为高浓度的辛酸以竞争方式置换了华法林和保泰松。发现华法林、舒洛芬和酮洛芬对HSA的对映体选择性结合是由于对映体在位点I的差异结合；舒洛芬和酮洛芬的主要结合位点没有对映体选择性。
