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，用于在快速发展的微米和纳米级传感和诊断设备领域控制生物分子识别过程。在这项研究计划的前八年中，我们已经开发出一种新的方法来控制生物分子识别，该方法是基于将“智能”聚合物线圈的受激塌陷（脱水）或扩张（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）耦合。在这种方法中，智能聚合物充当天线和致动器，以感知信号并对其做出响应，从而控制生物识别事件。它们在线圈尺寸和物理性质方面的特征性尖锐响应对pH、温度和/或电磁辐射在窄范围内或在特定波长下的微小变化允许快速和精确地控制分子事件。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分子开关与亲和蛋白质，配体和酶，以及开发新的策略，释放捕获的目标命令，并为“分子匹配”，选择性和可逆地汇集在一起的特定的，相互作用的分子组分在复杂的混合物。这些目标背后的分子工程跨越复杂的聚合物设计和合成以及蛋白质和DNA工程，并将刺激响应聚合物的功能特性与配体结合口袋、活性位点和受体-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.