含有氧沙的宏循环的细胞透
Sungjoon Huh1, Nefeli Batistatou2, Jing Wang2
1Davenport Research Laboratories, University of Toronto 80 St. George St Toronto Ontario M5S 3H6 Canada andrei.yudin@utoronto.ca.
RSC chemical biology
|April 5, 2024
概括
含氧化 (Odz) 的循环显示高细胞透率,受侧链位置和标签的影响. 尽管如此,它们在人造膜上表现出低的被动透性.
科学领域:
- 药用化学 医学化学
- 生物物理学的生物物理.
- 药物发现 药物发现 药物发现
背景情况:
- 被动膜透性对于药物发现和生物探针开发至关重要.
- 了解细胞透机制是设计有效治疗剂的关键.
研究的目的:
- 为了研究含有氧化 (Odz) 的循环的细胞透能力.
- 为了将体结构和形状与细胞透性和被动膜传输相关联.
主要方法:
- 甲基透测试用于评估细胞透.
- 使用溶液核磁共振 (NMR) 来确定形状.
- 使用人工膜的实验评估了被动透性.
主要成果:
- 奥兹循环表现出高细胞透率,取决于侧链定位和标签.
- 溶液NMR揭示了Odz循环采用β-转变形态.
- 通过人工膜观察到高细胞透率和低被动透率之间的差异.
结论:
- Odz循环可以设计为高细胞透性,为细胞透性循环设计提供潜在的支架.
- 在控制细胞透和被动透性方面,形状敏感的宏循环存在挑战.
- 这些发现强调了体结构,构造和膜运输之间的复杂相互作用.
相关概念视频
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
521
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
521
Cellular Membranes and Drug Transport
506
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
506
Pore Transport and Ion-Pair Transport
437
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
437
Physiological Barriers
3.5K
Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
3.5K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.3K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
1.3K
Factors Influencing Drug Absorption: Drug Dissolution
483
The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
483


