Control of Protein-Binding Kinetics on Synthetic Polymer Nanoparticles by Tuning Flexibility and Inducing Conformation Changes of Polymer Chains
Control of Protein-Binding Kinetics on Synthetic Polymer Nanoparticles by Tuning Flexibility and Inducing Conformation Changes of Polymer Chains
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DOI：
10.1021/ja306053s
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发表时间：
2012-09-19
影响因子：
15
通讯作者：
Miura, Yoshiko
中科院分区：
文献类型：
--
作者：
Hoshino, Yu;Nakamoto, Masahiko;Miura, Yoshiko
虽然已经发表了许多程序来创建具有对靶生物大分子的固有亲和力的合成聚合物纳米颗粒（NP），但是很少有关于控制靶识别的结合动力学的策略的报道。在这里，我们报告了一种酶模拟策略，以控制结合/解离速率常数的纳米粒子，通过多点相互作用结合蛋白质，通过利用温度响应的线圈小球相变的聚-N-异丙基丙烯酰胺（PNIPAm）为基础的纳米粒子。具有“柔性”无规卷曲构象的PNIPAm NPs具有比具有“刚性”小球构象的NPs更快的结合速率;然而，解离速率常数保持不变，导致更强的亲和力。“柔性”纳米粒子的解离速率被“诱导拟合”型构象变化的聚合物周围的线圈-小球相变温度，导致在最稳定的NP-蛋白质复合物的形成减速。这些结果为设计具有定制结合动力学和平衡常数的塑料抗体提供了指导。
Although a number of procedures to create synthetic polymer nanoparticles (NPs) with an intrinsic affinity to target biomacromolecules have been published, little has been reported on strategies to control the binding kinetics of target recognition. Here, we report an enzymemimic strategy to control binding/dissociation rate constants of NPs, which bind proteins through multipoint interactions, by taking advantage of the temperature-responsive coil-globule phase transition of poly-N-isopropylacrylamide (PNIPAm)-based NPs. PNIPAm NPs with a "flexible" random-coil conformation had a faster binding rate than NPs with a "rigid" globule conformation; however, the dissociation rate constant remained unchanged, resulting in stronger affinity. The dissociation rate of the "flexible" NPs was decelerated by the "induced-fit"-type conformation change of polymers around the coil-globule phase transition temperature, resulting in the formation of the most stable NP-protein complexes. These results provide a guide for designing plastic antibodies with tailor-made binding kinetics and equilibrium constants.