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相关概念视频

Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
What are Membranes?01:24

What are Membranes?

A cell's plasma membrane demarcates the cell's borders and determines the nature of its interaction with the environment. Cells exclude certain substances, take in others, and excrete some others in controlled quantities. The plasma membrane must be flexible to allow certain cells, such as red and white blood cells, to change their shape while passing through narrow capillaries. These are the more obvious plasma membrane functions. In addition, the plasma membrane's surface carries markers that...
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
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Two-Dimensional Microscopy in Microbiology

Two-dimensional (2D) microscopy encompasses a range of optical techniques that capture images within a single focal plane, offering detailed representations of microscopic structures. These techniques are essential in biological and medical research, enabling the visualization of cellular and subcellular structures with different levels of contrast and specificity.There are several major types of 2D microscopy, each with strengths and applications.Bright-Field MicroscopyBright-field microscopy...

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一个具有双功能的分子,它显示了取决于环境的细胞活动.

Patrick D Braun1, Katherine T Barglow, Yun-Ming Lin

  • 1Department of Chemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

Journal of the American Chemical Society
|June 19, 2003
PubMed
概括

一个新的双功能分子,MTXSLF,抑制二叶酸减少酶 (DHFR). 它的有效性是通过FKBP结合来调节的,证明了控制药物活性的新策略.

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科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 药物发现 药物发现 药物发现

背景情况:

  • 叶酸二酸减少酶 (DHFR) 是叶酸代谢中的一个关键酶,对于DNA合成至关重要.
  • 甲托雷克萨特 (MTX) 是一种强大的DHFR抑制剂,用于化疗.
  • FKBP是一种参与各种细胞过程的蛋白质,已知可以结合特定的连接体.

研究的目的:

  • 设计和合成一种双功能分子 (MTXSLF),将甲基酸与FKBP配体结合起来.
  • 研究FKBP对MTXSLF对人类和Plasmodium falciparum DHFR的抑制活性的影响.
  • 探索一种通过与非标蛋白相互作用来调节药物疗效的新策略.

主要方法:

  • 双功能分子MTXSLF的化学合成.
  • 在体外酶定量测试以评估DHFR抑制.
  • 在相关模型中进行体内实验,以评估药物疗效和FKBP影响.

主要成果:

  • 在体外,MTXSLF有效地抑制了人类的DHFR.
  • 人类FKBP的存在显著降低了MTXSLF对人类DHFR的疗效,这是由于高度亲和力和度.
  • 在体外,MTXSLF抑制了Plasmodium falciparum DHFR,在体内,Plasmodium FKBP的影响最小.

结论:

  • MTXSLF的设计展示了一种通过利用与二次蛋白 (FKBP) 的相互作用来控制药物活性的策略.
  • 非目标蛋白 (FKBP) 的结合亲和力和度是调节双功能分子疗效的关键因素.
  • 这种方法为微调合成化合物的生物活性提供了一个多功能平台.