意在通过转移素受体进行受体介导的细胞转移的附体分子
Linnea Charlotta Hjelm1, Hanna Lindberg1, Stefan Ståhl1
1Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden.
Pharmaceuticals (Basel, Switzerland)
|July 29, 2023
概括
研究人员开发了针对转移素受体-1 (TfR) 的新型附体分子,以增强跨血脑屏障的药物输送. 这些分子显示出作为治疗中枢神经系统疾病的大脑穿机的潜力.
科学领域:
- 神经科学是一个神经科学.
- 生物技术是生物技术.
- 药物运输 药物运输 药物运输
背景情况:
- 中枢神经系统 (CNS) 生物药物开发在实现大脑药物输送方面面临重大挑战.
- 受体介导的细胞转移,特别是针对转移素受体-1 (TfR),是增强大脑吸收的关键策略.
研究的目的:
- 开发新的附体分子,专门与转移素受体-1 (TfR) 结合.
- 设计具有改进性质的有形体变体,以作为大脑穿机的潜在用途.
主要方法:
- 体显示技术被用来选择针对人类TfR的附体分子.
- 评估了结合亲和性,交叉反应性和细胞相互作用.
- 单氨基酸突变发生和体外透孔试验被用于评估和改善亲体变异.
主要成果:
- 选择的附体分子表现出与人类TfR的特定结合以及与小鼠TfR的交叉反应性.
- 候选人显示与转激素的非竞争性结合,并与表达TfR的大脑内皮细胞结合.
- 第二代变种在体外表现出增强的特性和转细胞酶能力.
结论:
- 成功开发出了新的TfR特异性附带体分子.
- 这些附体分子充满希望,作为大脑的穿车,可以增加中枢神经系统中化合物的吸收.
- 需要进一步研究它们在治疗中枢神经系统疾病中的应用.
相关概念视频
The Early Endosome: Endocytosis of Transferrin
3.3K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
3.3K
Receptor-mediated Endocytosis
104.7K
Overview
104.7K
Transcytosis of IgG
2.8K
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
2.8K
Membrane Asymmetry Regulating Transporters
4.6K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
4.6K
Carrier-Mediated Transport
470
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
470
Facilitated Diffusion
510
The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
510


