Dendrimers Bind Human Serum Albumin
Dendrimers Bind Human Serum Albumin
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DOI：
10.1021/jp9011119
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发表时间：
2009-05-14
影响因子：
3.3
通讯作者：
Tajmir-Riahi, H. A.
中科院分区：
文献类型：
--
作者：
Froehlich, E.;Mandeville, J. S.;Tajmir-Riahi, H. A.
树枝状大分子是一种人工合成的高度支化的球形大分子，具有纳米级的尺寸，在DNA和药物传递系统中具有潜在的应用。人血清白蛋白（HSA）是体内递送多种内源性化合物和药物的主要转运蛋白。本研究的目的是在生理条件下，使用恒定的蛋白质浓度和各种树枝状聚合物组合物，检查人血清白蛋白与几种树枝状聚合物如mPEG-PAMAM（Q3）、mPEG-PAMAM（G4）和PAMAM（G4）的相互作用。采用红外光谱、紫外-可见光谱、圆二色光谱和荧光光谱等方法分析了大分子的结合方式、结合常数以及树枝状大分子络合对HSA稳定性和构象的影响。结构分析表明，树枝状聚合物通过多肽极性基团（亲水性）结合HSA，结合聚合物的数量（n）为1.08（mPEG-PAMAM-G3）、1.50（mPEG-PAMAM-G4）和0.96（PAMAM-G4）。估计的总体结合常数为KmPEG-G3 = 1.3（+/-0.2）x 10（4）M-1，KmPEG-G4 = 2.2（+/-0.4）x 10（4）M-1，KPAMAM-G4 = 2.6（+/-0.5）x 10（4）M-1。HSA构象被树枝状聚合物改变，α-螺旋大幅减少，无规卷曲和转弯结构增加，表明部分蛋白质展开。
Dendrimers are synthetic, highly branched, spherical macromolecules with nanometer dimensions and potential applications in DNA and drug delivery systems. Human serum albumin (HSA) is a major transporter for delivering several endogenous compounds and drugs in vivo. The aim of this study was to examine the interaction of human serum albumin with several dendrimers such as mPEG-PAMAM (Q3), mPEG-PAMAM (G4), and PAMAM (G4) at physiological conditions, using constant protein concentration and various dendrimer compositions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods were used to analyze macromolecule binding mode, the binding constant and the effects of dendrimers complexation on HSA stability and conformation. Structural analysis showed that dendrimers bind HSA via polypeptide polar groups (hydrophilic) with number of bound polymer (n) 1.08 (mPEG-PAMAM-G3), 1.50 (mPEG-PAMAM-G4), and 0.96 (PAMAM-G4). The overall binding constants estimated were of KmPEG-G3 = 1.3 (+/-0.2) x 10(4) M-1, KmPEG-G4 = 2.2 (+/-0.4) x 10(4) M-1, and KPAMAM-G4 = 2.6 (+/-0.5) x 10(4) M-1. HSA conformation was altered by dendrimers with a major reduction of alpha-helix and increase in random coil and turn structures suggesting a partial protein unfolding.