新型α-Conotoxins的合成和生物活性来源于本土波利尼西亚形牛的新型α-Conotoxins
Yazid Mohamed Souf1, Gonxhe Lokaj2, Veeresh Kuruva3
1CRIOBE, UAR CNRS-EPHE-UPVD 3278, Université de Perpignan Via Domitia, 58 Avenue Paul Alduy, 66860 Perpignan, France.
Marine drugs
|June 27, 2023
概括
来自马奎萨斯群岛牛的两个新型α-conotoxins,GaIA和AdIA被合成和表征. 它们对大鼠尼古丁乙胆受体 (nAChRs) 具有强大的抑制活性,有助于理解nAChR亚型.
科学领域:
- 海洋生物学 海洋生物学
- 神经科学是一个神经科学.
- 药用化学 医学化学
背景情况:
- α-Conotoxins是研究尼古丁性乙胆受体 (nAChRs) 的关键工具.
- 发现新的α-conotoxins提供了关于nAChR在各种生理和病理过程中的作用的见解.
- 来自马奎萨群岛特有牛 (Conus gauguini,Conus adamsonii) 的毒液是生物活性的丰富来源.
研究的目的:
- 为了合成和描述两个新型α-conotoxins,GaIA和AdIA.
- 调查GAIA和AdIA与老鼠nAChRs的药理学概况.
- 为了解α-conotoxin结构-活性关系,为设计选择性药理工具做出贡献.
主要方法:
- 单二硫化键合成利用2-二 (NBzl) 保护组进行区域选择性氧化.
- 电生理学测试以确定合成的毒素的效力和选择性.
- 对GaIA和AdIA的α-conotoxin折叠 [Cys 1-3; 2-4] 的表征.
主要成果:
- 成功合成和表征GaIA和AdIA与所需的α-conotoxin折叠.
- GAIA和AdIA都表现出对大鼠nAChRs的强烈抑制作用.
- 在肌肉 nAChR (IC50 = 38 nM) 中,GaIA 的活性最高,而在神经元 α6/3 β2β3 亚型 (IC50 = 177 nM) 中,AdIA 的活性最高.
结论:
- 这项研究成功地合成和表征了新型α-毒素GaIA和AdIA.
- 对于不同的nAChR亚型,GaIA和AdIA显示出不同的选择性概况.
- 这些发现增强了对α-conotoxin结构-活性关系及其作为选择性药理学探针的潜力的理解.
相关概念视频
Physical Properties of Amines
3.3K
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
3.3K
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
2.3K
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...
2.3K
Neurochemical Transmission: Sites of Drug Action
2.5K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.5K
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
1.1K
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
The direct-acting...
1.1K
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.1K
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...
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...
3.1K
Conjugated Proteins
18.4K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.4K


