ORGANIC AND BIO-ORGANIC CHEMISTRY

私家侦探的直接职业目标是获得技能，而不是发展 在他的本科和研究生工作中， 做“生物有机”研究 其中包括收集和分析 动力学和热力学数据以及实验和 生物聚合物研究的理论要素。 具体 需要这些技能的项目目前正在进行中， 描述了 其中包括： 1. 活性氧清除剂的研究 巯基组氨酸。 初步结果显示， 出现的物质表明它们是O2-，H2O2， 烷氧基和氮氧自由基。 进一步的研究将提供 率和机制，这些过程中，有用的信息 对抗炎症、衰老、辐射损伤和癌症。 2. DNA动力学 一个不受干扰的， 氮氧自旋探针已被合成地并入到 双链DNA十二聚体。 该探测器具有很大的潜力， 报告DNA的局部动态， 构象、介质（盐、温度）和碱基序列。 进一步的研究，包括DNA的动力学，药物-DNA复合物 被提议。 3. DNA交联的序列特异性。 几个重要 药物通过共价交联DNA发挥其作用。 的 氮霉素和丝裂霉素是实例。 迄今为止， 不可能阐明序列特异性， 交联反应。 解决这个问题的一个简单方法是 提出了 4. 肽构象。 设计大分子的能力 包含精确定义的几何形状和功能 能够创造新的催化剂和受体。 一 自然界使用的解决这个问题的方法是肽折叠。 可合成的肽不采用稳定的结构。 我们建议使用一个独特的环肽终止残基 用来启动一个短的α-螺旋

The P.I.'s immediate career goal is to acquire skills not develop during his undergraduate and graduate work which are necessary to do "bioorganic" research. These include collection and analysis of kinetics and thermodynamics data and experimental and theoretical elements of research on biopolymers. Specific projects which require these skills are currently underway, and are described. These include: 1. Study of a new family of active oxygen scavengers, the mercaptohistidines. Preliminary results on these naturally occurring substances indicate that they scavenge O2-., H2O2, alkoxy radicals, and nitroxide radicals. Further study will provide rates and mechanisms for these processes, information useful in combatting inflammation, aging, radiation damage, and cancer. 2. DNA Dynamics. A non-perturbing and rigidly tethered nitroxide spin probe has been synthetically incorporated into a duplex DNA dodecamer. This probe has a significant potential for reporting on local dynamics of DNA as a function of conformation, medium (salt, temperature), and base sequence. Further studies, involving dynamics of DNA, drug-DNA complexes are proposed. 3. Sequence Specificity of DNA Crosslinking. Several important drugs exert their effect by covalently cross-linking DNA. The nitrogen mustards and mitomycins, are examples. It has thus far not been possible to elucidate the sequence specificity for the cross-linking reactions. A simple solution to this problem is proposed. 4. Peptide Conformation. The ability to design large molecules containing precisely defined geometric shape and functionality would enable the creation of new catalysts and receptors. One solution to this problem, used by nature, is peptide folding. synthetically accessible peptides do not adopt a stable structure. We propose using a unique cyclic peptide terminating residue designed to initiate a short alpha-helix.