CHEMICAL & BIO-ORGANIC STUDIES OF VISION & PHOTOTAXIS

了解视觉传导、漂白适应、 和微生物趋光性都是非常基本的问题 生命的进程。如果可能的话，我们只能达成谅解。 通过各个领域的研究人员的努力，几乎涵盖了 整个科学领域。我们的努力将集中在为 这一非常困难的领域主要通过有机和生物有机方法。 因此，它必然会以解释和理解 在有机结构基础上的现象。和过去一样，我们的主要工具 将使用合成的视网膜类似物，其结构已经被 旨在使它们能够解决这些复杂问题的特定方面 现象。我们已经做了90多种不同的类比，这还不包括 顺式/反式异构体作为单独的化合物。具体地说，我们将调查 下列主题：(A)视觉色素的三级结构 视紫红质。这是一种膜蛋白，尽管做了很多努力，但它并没有 都是结晶的。我们正在尽最大努力制定 利用新近发展起来的高效光亲和法研究三级结构 标签，它将被放置在生色团的关键位置。(B) 漂白适应机制。这种广为人知的现象要少得多 比转导机制更能被理解。我们发现了一种很好的化学物质 它将第一次给我们提供化学手柄 研究生色团的结构因素导致 漂白。(C)维生素A异构化为11-顺式视网膜， 视觉色素发色团，是最近进行的重要步骤 发现了酶异构酶。通过将不同的类比与 异构酶方面，我们计划详细研究异构酶的作用机制。 (D)嗜盐细菌H.halobium的趋光性取决于两个 视网膜蛋白，感觉性视紫红质-I和11，它们引起诱人和 鞭毛的排斥运动。再一次，视网膜的合并 这些光感受器的类似物为我们提供了强大的工具来 研究导致鞭毛移动的基本机制。(D) 趋光性单细胞藻衣藻光感受器 最独特的是它是由视网膜类似物激活的，在 双键是固定的，因此不会发生异构化。 此外，趋光性甚至由简单的分子诱导，如 己醛。我们计划分离出足够数量的感光器 蛋白质，通过基因组手段或类似物掺入和 分子生物学，使体外生化和生物物理 可以通过测量来解释这些最意想不到的结果。

Understanding the mechanisms of visual transduction, bleaching adaptation, and microbial phototaxis are all very basic questions intimately related to the process of life. An understanding, if possible, can only be achieved through the efforts of researchers in various areas covering almost the entire field of science. Our efforts will be focused in contributing to this very difficult field mainly through organic and bioorganic approaches. Thus it will necessarily be centered in interpreting and understanding the phenomena on an organic structural basis. As in the past, our major tool will be to use synthetic retinal analogs, the structures of which have been designed so that they can solve specific aspects of these complex phenomena. We have made over 90 different analogs, not counting the cis/trans isomers as separate compounds. Specifically we will investigate the following topics: (a) The tertiary structure of the visual pigment rhodopsin. This is a membrane protein, and despite many efforts it has not been obtained crystalline. We are putting a major effort in mapping out the tertiary structure by a recently developed efficient photoaffinity label, which will be placed in critical sites of the chromophore. (b)The mechanism of bleaching adaptation. This well-known phenomenon is far less understood than the transduction mechanism. We have found a good chemical handle which will for the first time give us a chemical handle to investigate the structural factors of the chromophore that lead to bleaching. (c) The isomerization of vitamin A to 11-cis-retinal, the visual pigment chromophore, is an important step performed by the recently discovered enzyme isomerase. By reacting various analogs with the isomerase, we plan to investigate the details of the isomerase mechanism. (d)The phototaxis of the halophilic bacterium H. halobium depends on two retinal proteins, sensory rhodopsin-I and 11, which cause attractive and repellent movements of the flagella. Again the incorporation of retinal analogs into these photoreceptors has provided us with powerful tools to study the basic mechanism leading to flagella movement. (d)The photoreceptor of the phototactic unicellular algae Chlamydomonas has been found to be most unique in that it is activated by retinal analogs in which the double bonds are fixed so that no isomerization can occur. Furthermore, phototaxis is even induced by simple molecules such as hexanal. We plan to isolate sufficient quantities of the photoreceptor protein, by genomic means or a combination of analog incorporation and molecular biology, so that in vitro biochemical and biophysical measurements can be performed to elucidate these most unexpected results.