相关实验视频

Updated: Jul 24, 2025

Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

Published on: August 16, 2016

超越五项规则:半性宏循环的透性评估

Marion L'Exact¹, Christian Comeau¹, Alix Bourhis¹

¹Institut de Pharmacologie de Sherbrooke, Département de Pharmacologie-Physiologie, Faculté de Médecine et des Sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada.

Biochimica et biophysica acta. Biomembranes

|July 3, 2023

概括

半性宏循环显示出有前途的膜透性,即使超过了利宾斯基的透性.

科学领域:

药用化学医学化学
药物发现药物发现药物发现
药理学药理学是指药理学的学科.

背景情况:

超越利宾斯基五项规则的化合物为以前无法治疗的目标提供了新的治疗可能性.
宏环在调节蛋白质-蛋白质相互作用方面是有效的,但它们的膜透性预测具有挑战性.
尽管存在结构上的约束,但宏循环具有形状的灵活性,可能提高它们穿越生物膜的能力.

研究的目的:

通过系统的结构修改,研究半性宏循环的结构-透性关系.
通过平行人造膜透性试验 (PAMPA) 合成和评估新型半基宏循环的被动膜透性.

主要方法:

合成56个半性宏循环,基于一个带有链接器的四种氨基酸支架.
整合结构修改,包括立体化学,N-甲基化和脂友性.
使用并行人工膜透性试验 (PAMPA) 评估被动膜透性.

主要成果:

几个半基宏循环显示出足够的被动透性,挑战了基于利宾斯基五项规则之外的属性的预期.
在位置2的N-甲基化和添加脂友基组到氨酸侧链显著改善了透性.
提高的透度与拓极表面积 (tPSA) 和3D-PSA的减少相关,这表明屏蔽效应.

结论:

半性宏循环可以表现出良好的膜透性,扩大它们作为治疗剂的潜力.
像N-甲基化和脂友群添加等结构修改是提高宏循环透性的有效策略.
观察到的透性增强可能与"黑式"行为有关,其中脂友性屏蔽促进了膜交叉的有利构造.

关键词:

宏观循环是一种宏观循环.膜运输是通过膜运输来实现的.这是NMR的NMR.被动扩散是一种被动扩散.酸是一种酸.透性透性的

更多相关视频

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers

Published on: September 19, 2022

相关概念视频

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

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...

Pore Transport and Ion-Pair Transport

Pore Transport and Ion-Pair Transport

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...

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...