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相关概念视频

Heterogeneous Catalysis01:22

Heterogeneous Catalysis

Heterogeneous catalysis involves a catalyst in a different phase from the reactants. It is a process where the catalyst and the reactants are in distinct phases, typically solid and gas or liquid.Most heterogeneous catalysts are metals, metal oxides, or acids. The list includes transition metals like iron (Fe), cobalt (Co), nickel (Ni), palladium (Pd), platinum (Pt), chromium (Cr), manganese (Mn), tungsten (W), silver (Ag), and copper (Cu). These metals possess partially vacant d orbitals that...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
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Types of Receptors: Cell Surface Receptors01:28

Types of Receptors: Cell Surface Receptors

Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are...
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Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
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Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
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化学细胞表面受体工程使用亲和导向的多价值器官催化剂.

Hangxiang Wang1, Yoichiro Koshi, Daishiro Minato

  • 1Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Kyoto 615-8510, Japan.

Journal of the American Chemical Society
|July 19, 2011
PubMed
概括

研究人员开发了先进的亲和导向的DMAP (4-dimethylaminopyridine) 催化剂,用于精确地对活细胞进行化学蛋白质修饰. 这种新的有机催化剂方法可以实现特异性化,并为药物发现创造功能光生物传感器.

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科学领域:

  • 化学生物学 化学生物学
  • 有机化学 有机化学
  • 生物化学 生物化学

背景情况:

  • 催化剂为化学蛋白质修饰提供了潜力,但应用主要局限于体外系统.
  • 以前的亲和度指导的DMAP (4-二甲基亚胺胺) 催化剂 (AGD) 显示出有希望的结果,但需要改进以获得更广泛的应用.
  • 在活细胞上开发特定蛋白质修饰方法对于生物研究和药物发现至关重要.

研究的目的:

  • 开发一种改进的有机催化剂系统,用于在活细胞表面对受体蛋白进行特定的化学化.
  • 为了提高蛋白质标签的效率和特异性,使用多价值亲和力引导的催化剂.
  • 创建一个功能性的光生物传感器,基于细胞表面受体用于药物查.

主要方法:

  • 通过将多个DMAP单元合到一个向蛋白质特定的配体,设计和合成了多价值亲和导向的DMAP (4-二甲基亚胺胺) 催化剂 (AGD).
  • 在试验室中评估催化剂效率,以对Src同质性2 (SH2) 域Congerin II和FKBP12.
  • 在活细胞上使用多价值AGD催化剂和优化的乙烯基捐赠体实现了布拉迪基宁B2受体 (B2R) 的选择性化学标记.
  • 构建了一个光生物传感器,使用标记B(2) R来检测连接物结合.

主要成果:

  • 在体外,AGD催化剂的多价值性显著提高了蛋白质化效率.
  • 成功地证明了活细胞表面的布拉迪基宁B2受体 (B2R) 的选择性化学标记.
  • 开发了一种功能性的基于B(2) R的光生物传感器,在对抗体连接体结合时具有增强的光.
  • 生物传感器可以根据特定的分子相互作用对光调节进行按需调节.

结论:

  • 开发的多价值亲和力引导催化剂为活细胞上特定化学蛋白质修饰提供了强大的工具.
  • 这种有机催化剂方法促进了用于药物发现和生物研究的基于细胞的生物传感器的构建.
  • 亲和导向多价值催化剂的设计策略为各种基于催化剂的蛋白质工程应用开辟了新的途径.