Chromatographic analysis of acetohexamide binding to glycated human serum albumin.
Chromatographic analysis of acetohexamide binding to glycated human serum albumin.
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DOI：
10.1016/j.jchromb.2010.08.021
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发表时间：
2010-10-15
影响因子：
3
通讯作者：
Hage, David S.
中科院分区：
文献类型：
--
作者：
Joseph, K. S.;Anguizola, Jeanethe;Jackson, Abby J.;Hage, David S.
关键词：
醋磺己脲是一种用于治疗II型糖尿病的药物，与血液循环中的人血清白蛋白（HSA）紧密结合。已经提出，某些药物与HSA的结合可能受到该蛋白质的非酶糖化的影响。本研究使用高效亲和色谱法来检查随着HSA的糖化增加而发生的乙酰己脲-HSA结合的变化。在前沿分析实验中发现，乙酰己脲与糖化HSA的结合可以用包含强和弱亲和力相互作用的双位点模型来描述。高亲和力相互作用的平均缔合平衡常数（Ka）在1.2-2.0 × 105 M−1的范围内，并且随着从正常到晚期糖尿病中可能发现的糖化水平的HSA的移动而增加。通过竞争研究发现，醋磺己脲结合在糖化HSA上的Sudlow位点I和II处。在Sudlow站点I处的醋磺己脲的Ka在从正常HSA到最低限度糖化的HSA中增加了40%，但是在到更高度糖化的HSA中随后降低回到接近正常值。在Sudlow位点II，醋磺己脲的Ka首先降低约40%，然后从正常HSA增加到最低限度糖化的HSA和更高度糖化的HSA。这一信息表明，在检查糖化作用对药物与HSA相互作用的影响时，进行前沿分析和位点特异性结合研究的重要性。
Acetohexamide is a drug used to treat type II diabetes and is tightly bound to the protein human serum albumin (HSA) in the circulation. It has been proposed that the binding of some drugs with HSA can be affected by the non-enzymatic glycation of this protein. This study used high-performance affinity chromatography to examine the changes in acetohexamide-HSA binding that take place as the glycation of HSA is increased. It was found in frontal analysis experiments that the binding of acetohexamide to glycated HSA could be described by a two-site model involving both strong and weak affinity interactions. The average association equilibrium constant (Ka) for the high affinity interactions was in the range of 1.2–2.0 × 105 M−1 and increased in moving from normal to HSA with glycation levels that might be found in advanced diabetes. It was found through competition studies that acetohexamide was binding at both Sudlow sites I and II on the glycated HSA. The Ka for acetohexamide at Sudlow site I increased by 40% in going from normal HSA to minimally glycated HSA but then decreased back to near-normal values in going to more highly glycated HSA. At Sudlow site II, the Ka for acetohexamide first decreased by about 40% and then increased in going from normal HSA to minimally glycated HSA and more highly glycated HSA. This information demonstrates the importance of conducting both frontal analysis and site-specific binding studies in examining the effects of glycation on the interactions of a drug with HSA.
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影响因子：
2.9
作者：
Jackson AJ;Xuan H;Hage DS
通讯作者：
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影响因子：
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作者：
Conrad, Mandi L.;Moser, Annette C.;Hage, David S.
通讯作者：
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影响因子：
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作者：
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通讯作者：
HAGE, DS
影响因子：
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作者：
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通讯作者：
R端ker, F
DOI：
10.1016/j.bbagen.2003.08.001
发表时间：
2003-10-13
影响因子：
3
作者：
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通讯作者：
Otagiri, M