Sisavath Nicolas, Le Saux Thomas, Leclercq Laurent, Cottet Hervé
Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-Université de Montpellier 1-Université de Montpellier 2 , place Eugène Bataillon CC 1706, 34095 Montpellier Cedex 5, France.
Langmuir. 2014 Apr 22;30(15):4450-7. doi: 10.1021/la5002144. Epub 2014 Apr 7.
This work aims at studying the interaction between human serum albumin and different generations of dendrigraft poly-L-lysine (DGL) in physiological conditions. The binding constants and stoichiometry of the interaction were successfully determined using frontal analysis continuous capillary electrophoresis. The effect of generation on the interaction was evaluated for the five first generations of DGL. An increase of the binding constant accompanied with a decrease of the HSA:DGL (1:n) stoichiometry and a decrease of the cooperativity with dendrimer generation was observed. These findings were in good agreement with the increase of ligand (DGL) size, the increase of electrostatic ligand-ligand repulsion, and the localization of two negatively charged interaction sites on the HSA. The effect of the ligand topology (linear vs dendrigraft) on the HSA interaction revealed that linear poly(L-lysine) leads to much lower stoichiometry compared to DGL of similar molar mass due to much higher flexibility and contour length.
这项工作旨在研究生理条件下人类血清白蛋白与不同代数的树枝状聚-L-赖氨酸（DGL）之间的相互作用。使用前沿分析连续毛细管电泳成功测定了相互作用的结合常数和化学计量。对前五代DGL评估了代数对相互作用的影响。观察到结合常数增加，同时HSA:DGL（1:n）化学计量减少，并且与树枝状聚合物代数的协同性降低。这些发现与配体（DGL）尺寸的增加、静电配体-配体排斥的增加以及HSA上两个带负电荷的相互作用位点的定位高度吻合。配体拓扑结构（线性与树枝状接枝）对HSA相互作用的影响表明，由于具有更高的柔韧性和轮廓长度，与类似摩尔质量的DGL相比，线性聚（L-赖氨酸）导致化学计量低得多。
