Synthetic Retinal Pigments and Binding Proteins

描述（由申请人提供）：我们的长期目标是确定类维生素A在视觉转导过程中的作用，并探索视网膜类似物在治疗类维生素A加工不当引起的疾病（如Leber黑蒙）中的潜力。我们的工作前提是，视网膜发色团（11-顺式视网膜）控制的生物化学和生理特性的视色素。我们的第一个目标是研究调节视网膜相互作用的视蛋白的结构决定因素。研究将确定：1）如果独特的红锥视蛋白性质是由于不存在锚定蛋白质C末端的棕榈酸酯基团，2）如果视蛋白上存在推定的二级类维生素A结合位点并且如果其完整性依赖于棕榈酸酯的存在，以及3）如果全反式视黄醇形成和从外节段的清除受视蛋白的结构特征控制，视蛋白/类视色素相互作用和光感受器形态。我们的第二个目的是研究视色素循环在视杆细胞和视锥细胞变性中的作用。研究将确定：1）如果视杆视蛋白磷酸化减缓了缺乏11-顺式视网膜的模型中视蛋白活性引起的变性，2）如果维生素A加工不当导致视锥视蛋白错误定位并最终导致视锥变性，以及3）如果光稳定，11-顺式视网膜类似物可以纠正这种视锥视蛋白错误定位并防止视锥变性。我们预计这些研究将为使用类维生素A化合物治疗因维生素A加工不当而导致的致盲性疾病提供合理的基础。 类维生素A，维生素A，是众所周知的是必不可少的视力。缺乏足够的维生素A用于视觉过程可能是由于饮食缺乏或未能正确处理这种化合物。我们正在研究维生素A在眼睛中的加工过程，并探索使用类维生素A化合物治疗因维生素A加工不当而导致的疾病的药物潜力。

DESCRIPTION (provided by applicant): Our long-term goal is to define the roles of retinoids in the visual transduction process and to explore the potential of retinal analogs in treating disorders resulting from improper retinoid processing, such as in Leber's amaurosis. Our working premise is that the retinal chromophore (11-cis retinal) controls the biochemical and physiological properties of visual pigments. Our first aim is to investigate the structural determinants in opsins that modulate retinal interactions. Studies will determine: 1) if the unique red cone opsin properties are due to the absence of a palmitate group anchoring the C-terminus of the protein, 2) if a putative secondary retinoid binding site on opsins exists and if its integrity is dependent on the presence of a palmitate, and 3) if all-trans retinol formation and clearance from the outer segment are controlled by structural features of opsins, the opsin/retinoid interactions and photoreceptor morphology. Our second aim is to investigate the role of retinoid cycling in rod and cone degeneration. Studies will determine: 1) if rod opsin phosphorylation slows the degeneration arising from opsin activity in models that lack 11-cis retinal, 2) if improper vitamin A processing leads to cone opsin mislocalization and eventual cone degeneration, and 3) if light-stable, analogues of 11-cis retinal can correct this cone opsin mislocalization and prevent cone degeneration. We anticipate that these studies will form a rational basis for using retinoid-like compounds to treat the blinding diseases that result from improper vitamin A processing. The retinoid, vitamin A, is known to be essential for vision. Lack of adequate vitamin A for the visual process can arise from dietary deficiency or through a failure of processing this compound properly. We are studying the processing of vitamin A in the eye and exploring the pharmaceutical potential of using retinoid-like compounds to treat diseases resulting from improper processing of vitamin A.