Engineering and Analysis of Pressure Sensitive Antibodies

9503227 Yarmush该项目是研究使用静水压力作为解离抗原-抗体复合物的温和而有效的手段，从而为设计在分离和/或传感应用中利用这种压力敏感性的策略提供合理的基础。 本研究主要包括三个方面：（1）利用高压荧光光谱技术对一组抗体的压力诱导现象进行基本的溶液相热力学和动力学表征;（2）旨在理解介导压力效应的分子机制的蛋白质工程研究;和（3）用固定化抗体进行热力学、动力学和压力循环研究，以开发用于大规模实际压力洗脱的操作策略。 除了为开发工程化和利用压力敏感抗体的策略提供合理的框架外，这项研究还可能导致对压力对蛋白质结构和功能影响的基本理解的进步。 ***

9503227 Yarmush This project is on research to study the use of hydrostatic pressure as a mild and effective means of dissociating antigen-antibody complexes, thus providing a rational basis for the design of strategies which utilize this pressure sensitivity in separation and/or sensing applications. The proposed studies include three aspects: (1) fundamental solution-phase thermodynamic and kinetic characterization of the pressure-induced phenomena for a panel of antibodies using high pressure fluorescence spectroscopy; (2) protein engineering studies directed at understanding the molecular mechanisms mediating pressure effects; and (3) thermodynamic, kinetic and pressure cycling studies with immobilized antibodies to develop operational strategies for practical pressure elution on a large scale. In addition to providing the rational framework for the development of strategies for engineering and utilizing pressure sensitive antibodies, this research could also result in advances in the fundamental understanding of pressure effects on protein structure and function. ***