IONOPHORE-CATALYZED CATION TRANSPORT

本提案的主要目标是评估 控制A23187催化阳离子迁移的速率和选择性 和离子霉素。 金属离子-离子载体的平衡和动力学研究 络合将在两相水-磷脂囊泡中进行 系统. 将采用光谱和电位技术 以确定络合物稳定常数。 停止流动和温度- 跳跃弛豫方法将用于研究络合动力学。 转运序列将采用囊泡双层系统测定。 速率限制运输步骤将确定从光谱 准稳态输运下载体分子的观测 条件 离子载体-膜相互作用的性质和动力学将是 通过补充的光谱和物理方法来定义。 这项工作 将联合收割机的荧光寿命、偏振和淬灭 紫外吸收圆二色性和表面化学技术 接近。 运输选择性的改变， 膜性能的系统变化和化学基础， 将研究电荷选择性传输。 理化 新型二价阳离子载体和A23187的表征 衍生工具将在时间允许的情况下进行。 建议的研究结果需要解释 离子载体的生物学作用，特别是与细胞 Ca ~（2+）控制。 这些发现将促进离子载体的使用， 在诸如心脏功能和控制的领域中的药理学药剂 高血压 具有有用和良好特性的新载体 科学界将可以获得这些财产。 的 运输机制和膜相互作用的工作将有助于我们 了解亲脂性化合物跨膜的运动。

The major goals of this proposal are to evaluate the factors which control the rate and selectivity of cation transport catalyzed by A23187 and ionomycin. Equilibrium and kinetic studies of metal ion-ionophore complexation will be conducted in biphasic water-phospholipid vesicle systems. Spectroscopic and potentiometric techniques will be employed to determine complex stability constants. Stopped flow and temperature- jump relaxation methods will be utilized to study complexation kinetics. Transport sequences will be determined employing vesicle bilayer system. The rate limiting transport steps will be identified from spectral observation of the carrier molecule under pseudo steady-state transport conditions. The nature and dynamics of ionophore-membrane interactions will be defined by complimentary spectroscopic and physical methods. This work will combine fluorescence lifetime, polarization and quenching techniques with UV absorption circular dichroism and surface chemical approaches. Alterations of transport selectivity arising from systematic variation of membrane properties and the chemical basis of charge selective transport will be studied. The physico-chemical characterization of novel divalent cation ionophores and A23187 derivatives will be undertaken as time allows. The results of the proposed studies are required to interpret the biological actions of ionophores, particularly with regard to cellular control by Ca2+. The findings will foster the use of ionophores as pharmacological agents in such areas as cardiac function and the control of hypertension. New carriers with useful and well characterized properties will become available to the scientific community. The transport mechanism and membrane interaction work will contribute to our understanding of the movement of lipophilic compounds across membranes.