PHYSICOCHEMICAL STUDIES OF BIOCHEMICAL REACTIONS

这个项目的主要目的是研究生物和生化。 使用物理化学技术的过程。像过去一样，我们的努力 将集中在测定上，主要是通过量热的方法 以及对这些过程的热力学的解释。 我们工作的一大部分将涉及热诱导的研究 蛋白质、核酸和脂类中的高级蛋白质过程 灵敏度差示扫描量热法(DSC)。力量和力量 目前，这项技术的适用性正在迅速扩大。为 例如，DSC提供了检查热稳定性的最佳手段 被设计来执行某些特定的药物功能的蛋白质， 并用于获取热力学数据，这些数据可以建议具体的方法 提高热稳定性。我们在蛋白质方面的DSC工作将继续 以研究突变的影响为中心，使用提供的材料 以供广泛的合作者使用。其中将包括， 葡萄球菌核酸酶，链霉菌枯草杆菌抑制物(SSI)， 硫氧还蛋白和细胞色素b562。 DSC在核苷酸方面的工作将包括研究合成的 三链DNA，以及各种核苷酸-蛋白质复合体 ITC的研究。 DSC为研究化合物的相变提供了一种很好的手段 脂类。研究结构不同寻常的纯合成脂质将 继续。添加材料(Ca~(++)，Mg~(++)，AlCl3， 硝基苯酯)对脂双层热致行为的影响 也将继续。 我们正在不断地增加对等温情况的利用 量热法(ITC)，在研究配体与蛋白质和 核酸，蛋白质与核酸的相互作用，如 例如，TRP抑制器-TRP操作员交互作用，以及其他 生化反应。

The broad aim in this project is the study of biological and biochemical processes using physicochemical techniques. As in the past, our efforts will be centered on the determination, primarily by calorimetric methods and the interpretation of the thermodynamics of such processes. A major fraction of our work will involve study of thermally-induced processes in proteins, nucleic acids and lipids by means of high sensitivity differential scanning calorimetry (DSC). The power and applicability of this technique is at present rapidly expanding. For example, DSC affords the best means for checking the thermal stability of proteins engineered to perform some specific pharmaceutical function, and for acquiring thermodynamic data which may suggest specific ways to improve the thermal stability. Our DSC work on proteins will remain centered on studying the effects of mutations using materials supplied to use by a wide range of collaborators. Included will be, among others, staphylococcal nuclease, streptomyces subtilisin inhibitor (SSI), thioredoxin and cytochrome b562. DSC work on nucleotides will include study of the unfolding of synthetic triple stranded DNA, and of various nucleotide-protein complexes also studies by ITC. DSC gives an excellent means for studying the phase transitions of lipids. Work on pure synthetic lipids of unusual structure will continue. Studies of the effects of added materials (Ca++, Mg++, AlCl3, nitrophenyl esters) on the thermotropic behavior of lipid bilayers will also be continued. We are making constantly increasing use of isothermal situation calorimetry (ITC), in studying the binding of ligands to proteins and nucleic acids, the interactions of proteins with nucleic acids, for example, the trp repressor-trp operator interaction, and other biochemical reactions.