Pyridoxal Photoenzymes for Organic Synthesis

用于有机合成的吡哆醛光酶

• 批准号: 10895745
• 负责人: Todd Kurt Hyster
• 金额: $ 20.25万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10895745
• 关键词: Pyridoxal; Photoenzymes; Organic; Synthesis

7. Project Summary The work described in this proposal aims to advance biocatalytic tools for use in the synthesis of medicinally valuable molecules. We will develop new reaction mechanisms for pyridoxal-dependent enzymes to enable the facile synthesis of non-canonical amino acids through photoexcitation of pyridoxal intermediates involved in the catalysis of threonine aldolase and serine hydroxymethyltransferase. The first goal is to photoexcite the PLP external aldimine enabling it to function as a photoacid. This mechanism will allow these enzymes to use a broader set of 𝛼-, 𝛽-, and 𝛾-amino acids as pronucleophiles. The second goal is to excite the PLP-quinonoid to access a more reducing excited state. This species can reduce alkyl halides, redox-active esters, and cyanoheterocyles to form radicals that can recombine with the PLP-quinonoid radical to produce various non-canonical amino acids. Collectively, these studies will provide a new tool for the synthesis of non- canonical amino acids and serve as the foundation for a new area in photoenzymatic catalysis. The methods and the goals proposed in the Specific Aims can streamline the synthesis of biological probes and drug targets, creating a significant benefit to human health and associated biomedical sciences.

7.项目摘要 本提案中描述的工作旨在推进生物催化工具用于合成 药用价值分子。我们将开发新的吡哆醛依赖酶的反应机制 通过吡哆醛中间体的光激发， 参与催化苏氨酸醛缩酶和丝氨酸羟甲基转移酶。第一个目标是 光激发PLP外部醛亚胺，使其能够起到光酸的作用。这一机制将使这些 酶使用更广泛的α-、β-和β-氨基酸作为亲核试剂。第二个目标是激发 PLP-quinidine进入更还原的激发态。该物种可还原烷基卤化物，具有氧化还原活性 酯和氰基杂环以形成可与PLP-醌自由基重组以产生 各种非标准氨基酸。总的来说，这些研究将为综合非 典型的氨基酸，并作为光酶催化新领域的基础。的方法 具体目标中提出的目标可以简化生物探针和药物靶标的合成， 对人类健康和相关的生物医学科学产生显著的益处。