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首页> 外文学位 >New probes of enzyme reaction mechanisms: Part I. Selenoxides as serine protease and esterase transition-state analogs. Part II. A new probe for radical intermediates in enzyme-catalyzed hydride transfers.
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New probes of enzyme reaction mechanisms: Part I. Selenoxides as serine protease and esterase transition-state analogs. Part II. A new probe for radical intermediates in enzyme-catalyzed hydride transfers.

机译：酶反应机制的新探针：第一部分：硒酸作为丝氨酸蛋白酶和酯酶过渡态类似物。第二部分酶催化氢化物转移中自由基中间体的新探针。

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These studies have focused on obtaining a better understanding of the mechanisms of action of enzymes. Enzymes are Nature's catalysts for the chemical reactions of life.;Part I introduces the concept of using selenoxide-containing compounds as transition-state (TS) analogs for serine proteases and a serine esterase. The selenoxide-containing compounds were found to be weak competitive inhibitors for these enzymes. An X-ray crystallographic study of the complex between p-amidinobenzyl phenyl selenoxide and trypsin was undertaken in collaboration with Professor James S. Remington. The expected covalent bond formation between the selenium of the selenoxide and the catalytically-essential active site serine, indicative of the selenoxide acting as a TS analog, was not observed. Possible explanations for this observation are presented.;The hydration of selenoxides has been studied extensively by NMR spectroscopy to aid in interpretation of the enzyme inhibition results. All the studies with different selenoxide molecules indicated that the formation of selenoxide hydrate is kinetically facile but not thermodynamically favored. It was discovered that solvent plays an important role in controlling the stability of alkyl selenoxides toward ;In this research, it was found that it is not feasible to incorporate a selenoxide in a peptide analog to serve as a substrate analog due to the inherent instability of this class of compounds. However, such compounds incorporating a selenoxide or sulfoxide into an amide (-C(=O)NHCH;In Part II, the mechanistic question of one step two-electron transfer vs. two sequential one-electron transfer for horse liver alcohol dehydrogenase (HLAD) catalyzed redox reactions was investigated. Quadricyclan-3-one and quadricyclan-3-ol were used as new probes for radical intermediates. No ring-opened products, diagnostic for a radical intermediate in catalysis, were detected. Model studies for quadricyclan-3-one under conditions involving one-electron reduction known to generate the putative radical intermediate were pursued as well. To this point, all the evidence favors direct hydride transfer for HLAD catalyzed redox reactions.
机译：这些研究集中于获得对酶作用机理的更好理解。酶是自然界中生命化学反应的催化剂。第一部分介绍了使用含硒氧化物的化合物作为丝氨酸蛋白酶和丝氨酸酯酶的过渡态（TS）类似物的概念。发现含硒氧化物的化合物是这些酶的弱竞争抑制剂。与James S. Remington教授合作进行了对-酰胺基苄基苯基亚硒酸酯和胰蛋白酶之间复合物的X射线晶体学研究。没有观察到硒氧化物的硒与催化必需的活性位点丝氨酸之间预期的共价键形成，表明硒氧化物充当TS类似物。提出了这一观察结果的可能解释。硒氧化物的水合已通过NMR光谱进行了广泛研究，以帮助解释酶的抑制结果。所有使用不同亚硒氧化物分子的研究都表明，水合硒氧化物的形成在动力学上很容易，但在热力学上却不那么有利。发现溶剂在控制亚硒酸烷基酯的稳定性方面起着重要作用；在该研究中，由于硒酸酯固有的不稳定性，将硒氧化物掺入肽类似物中作为底物类似物是不可行的。这类化合物。然而，这类化合物将亚硒酸盐或亚砜掺入酰胺（-C（= O）NHCH;在第二部分中，对于马肝醇脱氢酶（HLAD）进行一步两电子转移与连续两次单电子转移的机理问题）研究了催化的氧化还原反应，将Quadricyclan-3-one和quadricyclan-3-ol用作自由基中间体的新探针，未发现可诊断催化自由基中间体的开环产物，对Quadricyclan-3的模型研究还寻求一种在涉及单电子还原的条件下生成已知的假定自由基中间体的方法，至此，所有证据都支持直接氢化物转移用于HLAD催化的氧化还原反应。

著录项

  • 作者

    Tsai, Pei.;

  • 作者单位

    University of Oregon.;

  • 授予单位 University of Oregon.;
  • 学科 Chemistry Biochemistry.;Chemistry Organic.
  • 学位 Ph.D.
  • 年度 1989
  • 页码 221 p.
  • 总页数 221
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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