Responsive Polymer-Engineered Protein Conjugates

响应性聚合物工程蛋白缀合物

基本信息

批准号：
7210639
负责人：
ALLAN S HOFFM
金额：
$ 34.53万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-02-01 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7210639
关键词：
Active Sites Affinity Antibodies Antigens Binding Binding Sites Biological Assay Cells Cellulases Characteristics Collaborations Complex Mixtures Condition Coupled Coupling DNA Dehydration Development Devices Diagnostic Electromagnetics Engineering Enzyme Inhibitor Drugs Enzyme Inhibitors Enzymes Event Free Radicals Length Life Ligand Binding Ligands Light Link Methods Microfluidic Microchips Modeling Molecular Molecular Weight Muramidase Oligonucleotides Peptides Polymers Process Property Protein Biosynthesis Protein Engineering Proteins Purpose Range Reaction Rehydrations Relative (related person)Research Research Personnel Signal Transduction Site Solubility Solutions Stimulus Streptavidin Structure Subtilisin Subtilisins System Techniques Technology Temperature Time antibody engineering base cellulase copolymer design design and construction desire enzyme activity enzyme model enzyme substrate inhibitor/antagonist innovation irradiation light scattering nanoscale new technology novel strategies physical property polymerization programs receptor response sensor size

项目摘要

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.

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级和纳米级传感和诊断设备领域控制生物分子识别过程。在该研究项目的前八年中，我们开发了一种控制生物分子识别的新方法，该方法基于将“智能”聚合物线圈的受刺激塌陷（脱水）或膨胀（再水化）与识别事件（例如蛋白质-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。它们的线圈尺寸和物理性质对窄范围或特定波长内的 pH、温度和/或电磁辐射的微小变化具有敏锐的响应，从而可以快速、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具有亲和蛋白、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目标，以及选择性地和可逆地将特定的、交互式的“分子匹配”结合在一起。复杂混合物中的分子成分。这些目标背后的分子工程涵盖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。