FREE RADICALS, LIPIDS AND ENZYME PHOTOACTIVATION

这项建议涉及到与人类健康有关的几个重要问题 和疾病状态。脂质过氧化作用与 低密度脂蛋白（LDL）引起的动脉斑块沉积， 因此，脂质过氧化作用的机制一直是研究的重点。 多注意。抗氧化剂，如维生素E是众所周知的发挥重要作用 在抑制LDL脂质过氧化中的作用。这项建议 解决了几个有关的自动氧化机制的问题， 脂质和脂蛋白。低密度脂蛋白自由基引发的时程研究 氧化给出了关于脂蛋白核心脂质氧化的数据， 可用于探测脂蛋白的抗氧化状态， 氧化大量胆固醇酯转化为游离胆固醇 参与自由基氧化的机制尚不清楚， 这将被调查。自由基化学的第二个方面， 这一建议解决的是自由基中立体化学的控制， 反应.本提案中提出的证据表明， 自由基加成反应中立体化学控制的一般问题 反应可以通过使用刘易斯酸和手性 双（恶唑啉）配体与恶唑烷酮丙烯酰胺一起沿着。激进 加成和烯丙基转移以优异的选择性发生。这 也允许探索对映选择性自由基反应 作为潜在的自由基过程， 该建议所涉及的第三个问题是设计和使用 光可逆酶抑制剂。这种策略提供了一种新颖的方式， 控制酶的活性与光和应用和扩展 提出了这种策略，特别是关于 凝血级联反应。 基于三重态的光活化策略是 建议这样可以敏化或淬灭光活化。一般 基于“凝固时间”的免疫测定系统的方法是 表明，作为一个中心特征，酶的光活化 战略

This proposal addresses several important issues relating to human health and disease states. Lipid peroxidation has been implicated in the deposition of arterial plaque from low density lipoproteins (LDL) and because of this, the mechanism of lipid peroxidation has been the focus of much attention. Antioxidants such as Vitamin E are known to play important roles in the inhibition of lipid peroxidation in LDL. This proposal addresses several questions relating to the mechanism of autoxidation of lipids and lipoproteins. Time course studies of initiated LDL free radical oxidations give data about oxidation of the lipoprotein core lipids that can be used to probe the antioxidant status of the lipoprotein undergoing oxidation. Substantial cholesterol ester conversion to free cholesterol attends free radical oxidation by a mechanism that is not understood but which will be investigated. A second aspect of free radical chemistry that this proposal addresses is the control of stereochemistry in free radical reactions. Evidence is presented in this proposal that suggests that the general problem of stereochemical control in free radical addition reactions can be solved by the use of Lewis acids and chiral bis(oxazoline) ligands along with oxazolidinone acrylamides. Radical additions and allyl transfers occur with excellent selectivity. This allows the exploration of enantioselective free radical reactions as well as potential free radical processes that are catalytic in the chiral reagent A third problem that this proposal addresses is the design and use of photoreversible enzyme inhibitors. This strategy provides a novel way to control enzyme activity with light and applications and expansion of this strategy are proposed, particularly with regard to the enzymes of the blood coagulation cascade. Triplet based photoactivation tactics are suggested so that photoactivation can be sensitized or quenched. General approaches to immunoassay systems based upon "coagulation times" are suggested that have as a central feature the enzyme photoactivation strategy.