Understanding the mechanism of two important cytochrome P450 catalysed reactions: dehydrogenation and C-C cleavage

了解两个重要的细胞色素 P450 催化反应的机制：脱氢和 C-C 裂解

• 批准号: DP140103229
• 负责人: Prof James De Voss
• 金额: $ 23.07万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2014
• 资助国家: 澳大利亚
• 起止时间: 2014-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP140103229
• 关键词: Understanding; mechanism; two; important; cytochrome

Cytochromes P450 are enzymes that play key roles in drug metabolism and biosynthesis. P450s often catalyse hydroxylation but also carry out important transformations such as dehydrogenation or carbon-carbon bond cleavage. Such reactions are pivotal in many biological pathways. This work will elucidate the mechanism of these transformations and the factors that facilitate their occurrence. This will mainly entail the synthesis of small organic mechanistic probes and determining the structure and stereochemistry of the product of enzymic oxidation. Understanding these mechanisms will allow us to predict when such reactions will occur, enabling their utilisation in for example drug design in the avoidance of the formation of toxic metabolites.

细胞色素P450是在药物代谢和生物合成中起关键作用的酶。P450经常催化羟基化，但也执行重要的转化，如脱氢或碳碳键断裂。这样的反应在许多生物途径中都是关键的。这项工作将阐明这些转变的机制和促进它们发生的因素。这将主要包括合成小的有机机理探针和测定酶氧化产物的结构和立体化学。了解这些机制将使我们能够预测这种反应何时发生，从而使它们能够在例如药物设计中用于避免有毒代谢物的形成。