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长链全氟烷酸与血清白蛋白的非共价相互作用。

Noncovalent interactions of long-chain perfluoroalkyl acids with serum albumin.

机构信息

Department of Civil and Environmental Engineering, Stanford University, Stanford, California 94305, USA.

出版信息

Environ Sci Technol. 2010 Jul 1;44(13):5263-9. doi: 10.1021/es101334s.

DOI:10.1021/es101334s
PMID:20540534
Abstract

Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K(a)) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10(-3)), corresponding to a high protein-water distribution coefficient (log K(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M(-1) for PFOA and PFNA and 10(4) M(-1) for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.

摘要

长链全氟烷酸(PFAAs)在生物体内的肝脏、肾脏和血液中的优先分布突出了 PFAA-蛋白相互作用在 PFAA 组织分布模式中的重要性。血清蛋白结合常数可能是一个有用的参数,可以用来描述 PFAAs 的生物累积潜力和体内生物利用度。在这项工作中,通过平衡透析定量测定了 PFAA-白蛋白复合物在很宽的 PFAA:白蛋白摩尔比范围内的结合常数(K(a))和结合化学计量比。通过平衡透析测定的模型蛋白牛血清白蛋白(BSA)与全氟辛酸(PFOA)或全氟壬酸(PFNA)的一级结合常数约为 10(6) M(-1),具有一个到三个主要结合位点。在生理 PFAA:白蛋白摩尔比(<10(-3))下,PFNA 与 BSA 或人血清白蛋白(HSA)的结合率大于 99.9%,对应的蛋白-水分配系数(log K(PW) > 4)较高。纳喷雾电离质谱(nanoESI-MS)数据显示,在 4:1 的 PFAA:白蛋白摩尔比下,PFAA-BSA 复合物具有多达八个占据的结合位点。通过 nanoESI-MS 估计的结合常数对于 PFOA 和 PFNA 约为 10(5) M(-1),对于全氟癸酸和全氟辛烷磺酸约为 10(4) M(-1)。这里报道的结果表明,在低 PFAA:白蛋白摩尔比下,通过特定的高亲和力相互作用进行结合。

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