IONOPHORE CATALYZED CATION TRANSPORT

该提案的主要目标是评估影响因素 控制 A23187 催化的阳离子传输的速率和选择性 和离子霉素。 金属离子-离子载体的平衡和动力学研究 络合作用将在双相水-磷脂囊泡中进行 系统。 将采用光谱和电位技术 确定复杂的稳定常数。 停止流动和温度- 将利用跳跃弛豫方法来研究络合动力学。 将使用囊泡双层系统来确定运输序列。 速率限制传输步骤将从光谱中识别 准稳态传输下载流子分子的观察 条件。 离子载体-膜相互作用的性质和动态将是 由互补的光谱和物理方法定义。 这部作品 将结合荧光寿命、偏振和猝灭 紫外吸收圆二色性和表面化学技术 接近。 运输选择性的改变引起的 膜特性的系统变化及其化学基础 将研究电荷选择性传输。 物理化学 新型二价阳离子离子载体和 A23187 的表征 衍生品将在时间允许的情况下进行。 拟议研究的结果需要解释 离子载体的生物作用，特别是在细胞方面 由Ca2控制。 这些发现将促进离子载体的使用 心脏功能和控制等领域的药物 高血压。 具有实用且特征良好的新型载体 性质将可供科学界使用。 的 运输机制和膜相互作用工作将有助于我们 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.