ENDORPHIN, PHENOTHIAZINE AND ENZYME SITES ON CALMODULIN

拟议的研究代表了一项综合的化学和物理化学研究。 阐明相关分子参数的方法 钙调蛋白与β-内啡肽、吩噻嗪、磷酸二酯酶、 钙和钒。内啡肽和内啡肽的直接结合研究 将进行吩噻嗪类药物的研究，以追求协同作用的本质 这一点已经被观察到了。化学研究将集中在差示踪迹上 钙调素AS中单个赖氨酸反应性的标记评估 受各种配体的影响。将进行可行性研究 用一种新的技术鉴定内啡肽结合位点 关于钙调蛋白和这些区域。将在ESR方面投入相当大的努力 自旋标记的钙调蛋白和钒-钙调蛋白络合物的光谱， 几个探针将被用来修饰钙调蛋白，并自旋标记 氯丙嗪-钙调蛋白复合体将被研究。这些研究 应提供有关钙调蛋白通过何种机制 与多种简单的配体和复杂的酶结合。

The proposed research represents an integrated chemical and physicochemical approach to elucidate the molecular parameters involved in the association of calmodulin with Beta-endorphin, phenothiazines, phosphodiesterase, calcium and vanadyl. Direct binding studies of endorphin and phenothiazines will be conducted to pursue the nature of the cooperativity that has been observed. Chemical studies will focus on differential trace labeling to assess individual lysine reactivities in calmodulin as influenced by the various ligands. A feasibility study will be undertaken using a novel technique for identification of the endorphin binding sites on calmodulin and the regions. Considerable effort will be devoted to ESR spectroscopy of spin labeled calmodulin and vanadyl-calmodulin complexes, several probes will be used to modify calmodulin, and spin labeled chlorpromazine-calmodulin complexes will be investigated. These studies should provide useful information on the mechanisms by which calmodulin can associate with a variety of simple ligands and complex enzymes.