FREE RADICALS, LIPIDS AND ENZYME PHOTOACTIVATION

该提案涉及与人类健康有关的几个重要问题。 和疾病状态。脂质过氧化被认为与 低密度脂蛋白(LDL)和动脉斑块的沉积 正因为如此，脂质过氧化机制一直是人们关注的焦点。 备受关注。众所周知，维生素E等抗氧化剂起着重要的作用 在抑制低密度脂蛋白脂质过氧化中的作用。这项建议 解决了与自氧化机制有关的几个问题 脂类和脂蛋白。低密度脂蛋白引发自由基时程研究 氧化作用提供了有关脂蛋白核心脂类氧化的数据 可用来探讨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 以一种未知的机制参与自由基氧化，但 我们将对此进行调查。自由基化学的第二个方面 本提案针对的是自由基中立体化学的控制。 反应。这项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 反应可以通过使用路易斯酸和手性来解决 二(恶唑啉)配体和恶唑烷酮丙烯酰胺。根部 加成反应和烯丙基转移反应具有很好的选择性。这 也允许探索对映体选择性自由基反应 作为潜在的自由基过程，在手性中是催化的 试剂本建议解决的第三个问题是设计和使用 光可逆酶抑制剂。这一策略提供了一种新的方式 利用光调控酶活性及其应用和扩展 这一策略是提出的，特别是关于 血液凝固级联反应。基于三重态的光激活策略是 建议这样可以敏化或猝灭光激活。一般信息 基于“凝血时间”的免疫分析系统的方法有 建议以酶的光活化为中心特征 策略。

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.