SYNTHETIC RETINAL PIGMENTS AND BINDING PROTEINS

我们的目标是了解视觉传导的过程。仅限 当这种机制被充分阐明后，一种设计 有意义的方法来治疗由视觉障碍引起的 这一转导过程的故障。我们的假设是 通过使用视网膜类似物来特异性地诱导深层变化 在视紫红质蛋白中，可能会修改 转导机制。我们的方法是使用类似于 原生发色团，11顺式视网膜，用于探测 启动可视流程。视网膜的类似物呈现出 获得有关内部变化的信息的独特机会 视紫红质蛋白本身，而不破坏自然系统。 通过使用各种类似物来测试特定的化学和 发色团与蛋白质的电子相互作用 建议在以下方面进行一系列实验 与其他实验室的合作：1)成立 脊椎动物活的离体光感受器的类似物 (虎蜥蜴)和一种无脊椎动物(鳗) 对离散电子事件的影响的研究 转导。2)G蛋白与磷酸二酯酶的相关性 模拟色素的变视紫质状态的激活。 3)确定发色团的确切位置 视紫红质和偏视紫质状态下的视觉色素 光亲和标记后进行质谱分析。4) 视网膜的结构-功能作用的研究在许多 视紫红质化学的一些方面。5)体外测定 无脊椎动物模拟色素的性质。 这些研究将产生更好的理解 可能具有重要意义的转导过程 某些人类疾病的过程。

Our goal is to understand the process of visual transduction. Only when this mechanism is fully elucidated can one design meaningful approaches to visual disorders arising from the malfunction of this transduction process. Our hypothesis is that by using retinal analogues to specifically induce changes deep within the rhodopsin protein, it may be possible to modify the transduction mechanism. Our approach is to use analogues of the native chromophore, 11-cis retinal, to probe the site at which the visual process is initiated. The retinal analogues present the unique opportunity to gain information on changes within the rhodopsin protein itself without disrupting the native system. By using a variety of analogues to test specific chemical and electronic interactions of the chromophore with the protein, we propose to undertake the following series of experiments in collaboration with other laboratories: 1) Incorporation of analogues into the living isolated photoreceptors of vertebrate (tiger salamander) and an invertebrate (Limulus) for the purpose of studying effects on the discrete electrical events in transduction. 2) Correlation of G protein and phosphodiesterase activation with metarhodopsin states of the analogue pigments. 3) Determination of the exact location of the chromophore within the visual pigment in the rhodopsin and metatrhodopsin states by photoaffinity labeling followed by mass spectral analysis. 4) Studies of the structure-function role of retinal in a number of aspects of rhodopsin chemistry. 5) Determination in vitro of the properties of invertebrate analogue pigments. These studies will generate a better understanding of the transduction process which may have important implications in certain human disease processes.