相关实验视频

Updated: Jun 14, 2025

Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate

Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate

Published on: April 24, 2018

一个更新的氧化丁氨酸化的结构

Jieye Lin¹, Guanhong Bu¹, Johan Unge²

¹Department of Biological Chemistry, University of California, 615 Charles E. Young Drive South, Los Angeles, CA, 90095, USA.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|September 3, 2024

概括

微晶电子衍射 (MicroED) 确定了oxybutynin的3D结构,改进了以前的X射线方法. 这一进步有助于对氧丁尼尼的理解.

科学领域:

晶体学晶体学是指结晶学.
结构生物学结构生物学
药理学药理学是指药理学的学科.

背景情况:

氧化丁氨酸是肌肉激素对膀过活的对手,几十年来缺乏明确的晶体结构.
之前的粉末X射线衍射 (PXRD) 研究显示出由于X射线诱导的光减光导致的不一致性.
样本准备和技术的局限性阻碍了结构阐明.

研究的目的:

为了确定oxybutynin化的实验3D结构.
为了研究 (R) -oxybutynin与M3肌肉蛋白受体 (M3R) 的结合机制.
为未来的药物开发提出M3R抗剂的通用构造.

主要方法:

微晶电子衍射 (MicroED) 用于3D结构的确定.
分子对接模拟用于分析蛋白质与药物相互作用.
与以前的粉末X射线衍射 (PXRD) 数据进行比较.

主要成果:

通过使用MicroED成功揭示了氧丁尼化的实验3D结构.
与之前报告的PXRD结构相比,显著改善.
确定了与M3R结合 (R) -oxybutynin相关的关键接触点和残留物.
在对抗剂结合时,揭示了M3R蛋白口袋内的构造变化.

结论:

微ED是一种强大的药物结构阐明技术,补充PXRD.
这项研究提供了有关氧化丁宁M3R结合机制的见解.
对于M3R抗剂,提出的普遍构造可以指导未来的药物设计和优化.
这项研究增强了对M3R抗剂的蛋白质药物相互作用的理解.

关键词:

微晶电子衍射 (MicroED) 是一种微晶电子衍射技术.分子对接的分子对接.氧丁尼尼 (Ditropan) 是一种抗氧化剂.蛋白质与药物相互作用拉塞米克水晶的使用方法

更多相关视频

Transcorporal Artificial Urinary Sphincter Cuff Placement in a Case Requiring Revision for Urethral Atrophy

Transcorporal Artificial Urinary Sphincter Cuff Placement in a Case Requiring Revision for Urethral Atrophy

Published on: June 16, 2022

Formation of Dispersible Taohong Siwu Tablets

Formation of Dispersible Taohong Siwu Tablets

Published on: February 3, 2023

相关概念视频

Antihypertensive Drugs: Thiazide-Class Diuretics

Antihypertensive Drugs: Thiazide-Class Diuretics

Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate...

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...

Factors Influencing Drug Absorption: Pharmaceutical Parameters

Factors Influencing Drug Absorption: Pharmaceutical Parameters

Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...

Drug Biotransformation: Overview

Drug Biotransformation: Overview

Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...