Department of Chemistry, China Agricultural University, Beijing 100193, China; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Key Laboratory of Pesticide Chemistry and Application Technology, Ministry of Agriculture, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
Ecotoxicol Environ Saf. 2012 May;79:238-246. doi: 10.1016/j.ecoenv.2012.01.009. Epub 2012 Jan 31.
The complexation between the primary vector of ligands in blood plasma, human serum albumin (HSA) and a toxic anthraquinone dye alizarin complexone, was unmasked by means of circular dichroism (CD), molecular modeling, steady state and time-resolved fluorescence, and UV/vis absorption measurements. The structural investigation of the complexed HSA through far-UV CD, three-dimensional and synchronous fluorescence shown the polypeptide chain of HSA partially destabilizing with a reduction of α-helix upon conjugation. From molecular modeling and competitive ligand binding results, Sudlow's site I, which was the same as that of warfarin-azapropazone site, was appointed to retain high-affinity for alizarin complexone. Moreover, steady state fluorescence displayed that static type and Förster energy transfer is the operational mechanism for the vanish in the tryptophan (Trp)-214 fluorescence, this corroborates time-resolved fluorescence that HSA-alizarin complexone adduct formation has an affinity of 10(5) M(-1), and the driving forces were found to be chiefly π-π, hydrophobic, and hydrogen bonds, associated with an exothermic free energy change. These data should be utilized to illustrate the mechanism by which the toxicological action of anthraquinone dyes is mitigated by transporter HSA.
通过圆二色性（CD）、分子建模、稳态和时间分辨荧光以及紫外/可见吸收测量，揭示了血液血浆中主要配体载体人血清白蛋白（HSA）与有毒蒽醌染料茜素络合酮之间的络合作用。通过远紫外 CD、三维和同步荧光对结合 HSA 的结构研究表明，HSA 的多肽链在结合后部分失稳，α-螺旋减少。从分子建模和竞争性配体结合结果来看，被指定为保留与茜素络合酮高亲和力的 Sudlow 位点 I 与华法林-阿扎丙宗的位点相同。此外，稳态荧光显示，静态类型和福斯特能量转移是色氨酸（Trp）-214 荧光消失的操作机制，这证实了时间分辨荧光，即 HSA-茜素络合酮加合物的形成具有 10(5) M(-1)的亲和力，驱动力主要是π-π、疏水和氢键，伴随着放热自由能变化。这些数据可用于说明 HSA 转运蛋白如何减轻蒽醌染料的毒理学作用的机制。
