Responsive Polymer-Engineered Protein Conjugates

描述(由申请人提供)： 我们研究的长期目标是开发新的组合物和技术，用于控制快速发展的微纳传感和诊断设备领域的生物分子识别过程。在这项研究计划的前八年中，我们开发了一种控制生物分子识别的新方法，该方法基于“智能”聚合物线圈的受激坍塌(脱水)或膨胀(再水化)与识别事件，如蛋白质-配体、酶-底物、蛋白质-蛋白质和DNA杂交反应。在这种方法中，智能聚合物既充当天线又充当执行器，感知信号并对其做出响应，从而控制生物识别事件。它们在线圈大小和物理性质方面对pH、温度和/或窄范围或特定波长的电磁辐射的微小变化做出了独特的敏锐反应，从而实现了对分子事件的快速和精确控制。我们称之为“分子开关”。我们在这里寻求继续开发和应用这种具有亲和力的蛋白质、配体和酶的分子开关，并开发新的策略来根据命令释放捕获的靶标，并开发用于选择性和可逆地将复杂混合物中特定的、相互作用的分子组分聚集在一起的“分子匹配”。这些目标背后的分子工程跨越了复杂的聚合物设计和合成以及蛋白质和DNA工程，并将刺激响应性聚合物的功能特性与配体结合口袋、活性部位和受体-配体序列的分子复杂性相匹配。

DESCRIPTION (provided by applicant): The long term objective of our research is to develop new compositions and technologies for controlling biomolecular recognition processes in the rapidly developing fields of micro- and nano-scale sensing and diagnostic devices. In the first eight years of this research program, we have developed a new approach to the control of biomolecular recognition that is based on coupling the stimulated collapse (dehydration) or expansion (rehydration) of the "smart" polymer coil with recognition events such as protein-ligand, enzyme-substrate, protein-protein and DNA hybridization reactions. In this approach, the smart polymers serve as both antennae and actuators, to sense signals and respond to them, leading to control of biorecognition events. Their characteristic sharp responses in coil size and physical properties to small changes in pH, temperature, and/or electromagnetic irradiation over narrow ranges or at specific wavelengths permits rapid and precise control of molecular events. We term this a "molecular switch". We seek here to continue the development and applications of such molecular switches with affinity proteins, ligands and enzymes, as well as to develop new strategies for releasing captured targets on command, and for "molecular matchmaking" that selectively and reversibly brings together specific, interactive molecular components in complex mixtures. The molecular engineering underlying these aims spans sophisticated polymer design and synthesis and protein and DNA engineering, and matches the functional properties of the stimuli-responsive polymers to the molecular complexities of ligand binding pockets, active sites, and receptor-ligand sequences.