Photoaffinity labeling of heme proteins with chemically modified prosthetic groups

用化学修饰的辅基对血红素蛋白进行光亲和标记

• 批准号: 131931335
• 负责人: Professor Dr. Thomas Lindel
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/131931335?language=en
• 关键词: Photoaffinity; labeling; heme; proteins; chemically

For the analysis of heme and molybdenum cofactor insertion into apoproteins novel chemistry-based tools are essential. Of particular interest will be diazirine-functionalized heme analogs that are to be analyzed in reconstitution experiments with apoproteins, in close collaboration with our partners within the PROTRAIN research group. Key challenge is the incorporation of diazirine moieties into cofactors or proteinogenic amino acids with minimal structural alteration. Ultimately, it is intended to interrupt the reconstitution by photolysis of the diazirine moieties liberating reactive carbenes. The apoproteins will be functionalized along the insertion channel and analyzed by LTQ-Orbitrap mass spectrometry. Heme derivatives will also be applied in the search for heme binding proteins employing novel fluorescent and photoactivatable linkers. Fluorescent trifunctional linkers will be investigated as tools for the identification of protein-protein interactions via label transfer. To be able to assess the cofactor load of redox enzymes containing the molybdenum cofactor (Moco) the total synthesis of the Moco degradation products Form A and B is addressed, which feature challenging pteridin-derived architectures.

为了分析血红素和钼辅助因子插入载脂蛋白，新的化学工具是必不可少的。与PROTRAIN研究小组的合作伙伴密切合作，特别感兴趣的将是在载脂蛋白重组实验中分析的重氮嘧啶功能化血红素类似物。关键的挑战是将重氮嘧啶部分结合到辅因子或蛋白质生成氨基酸中，并使结构改变最小。最终，它的目的是中断重氮嘧啶部分的光解释放活性碳的重构。载脂蛋白将沿插入通道功能化，并通过LTQ-Orbitrap质谱分析。血红素衍生物也将应用于寻找血红素结合蛋白，利用新的荧光和光激活的连接物。荧光三功能连接将被研究作为工具，通过标签转移鉴定蛋白质-蛋白质相互作用。为了能够评估含有钼辅助因子（Moco）的氧化还原酶的辅助因子负荷，研究了Moco降解产物形式A和B的全合成，它们具有挑战性的翼黄素衍生结构。

项目成果

Quantum chemical calculation of 19F NMR chemical shifts of trifluoromethyl diazirine photoproducts and precursors

三氟甲基二氮丙啶光产物和前体的 19F NMR 化学位移的量子化学计算

• DOI: 10.1016/j.jfluchem.2014.06.027
• 发表时间: 2014
• 期刊: Journal of Fluorine Chemistry
• 影响因子: 1.9
• 作者: B. Raimer;P. G. Jones;T. Lindel
• 通讯作者: T. Lindel

Enantioselective Synthesis and Photoreactivity of a Diazirinyl-substituted (R)-β-Phenylalanine

二氮丙啶取代的 (R)-β-苯丙氨酸的对映选择性合成和光反应性

• DOI: 10.5560/znb.2014-4152
• 发表时间: 2014
• 期刊: Zeitschrift für Naturforschung B
• 作者: J.-N. Schäckermann;T. Lindel
• 通讯作者: T. Lindel

Synthesis, Stability, and Photoreactivity of Diazirinyl-Substituted N-Heterocycles Based on Indole, Benzimidazole, and Imidazole

• DOI: 10.1002/ejoc.201402354
• 发表时间: 2014-09
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Björn Raimer;T. Wartmann;P. Jones;T. Lindel

Photoactivation of (p-methoxyphenyl)(trifluoromethyl)diazirine in the presence of phenolic reaction partners.

• DOI: 10.1002/chem.201203479
• 发表时间: 2013-05
• 期刊: Chemistry
• 作者: Björn Raimer;T. Lindel

Water compatible photoarylation of amino acids and peptides.

氨基酸和肽的水相容性光芳基化

• DOI: 10.1002/chem.201402959
• 发表时间: 2014
• 期刊: Chemistry
• 作者: A. Sudakow;U. Papke;T. Lindel
• 通讯作者: T. Lindel