ORGANIC AND BIO-ORGANIC CHEMISTRY

私家侦探S近期的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。这些包括收集和分析 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。特定的 需要这些技能的项目目前正在进行中，以及 都被描述了。这些措施包括： 1.新的活性氧清除剂家族的研究 硫代组氨酸。关于这些自然的初步结果 产生的物质表明它们清除O2-.，H2O2， 烷氧基和氮氧基。进一步的研究将提供 这些流程的费率和机制，有助于 对抗炎症、衰老、辐射损伤和癌症。 2.DNA动力学。一种不受干扰和严格捆绑的 氮氧化物自旋探测器已被合成并入一种 双链DNA十二聚体。这个探测器有很大的潜力 关于DNA局部动态的报告，作为 构象、介质(盐、温度)和碱基序列。 进一步研究，包括DNA、药物-DNA复合体的动力学 都被提出了。 3.DNA交联的序列特异性。几个重要的 药物通过共价交联DNA发挥作用。这个 氮素芥末和丝裂霉素就是例子。到目前为止，它已经 无法阐明该基因的序列特异性 交联式反应。这个问题的一个简单解决方案是 建议。 4.多肽构象。设计大分子的能力 包含精确定义的几何形状和功能 将能够创造出新的催化剂和受体。一 这个问题的解决方案，自然界使用的是多肽折叠。 可合成的多肽并不采用稳定的结构。 我们建议使用一种独特的环肽终止残基 被设计成启动一个短的阿尔法螺旋。

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.