Abstract
The atomic determination of the acetylcholine binding protein (AChBP), a molluscan cholinergic protein, homologous to the amino-terminal extracellular domain of nicotinic receptors (nAChRs), offers opportunities for the modeling of the acetylcholine binding site and its ligands. Recently, we constructed three-dimensional models of the Nterminal part of nAChR and docked in the putative ligand-binding pocket, different agonists (acetylcholine, nicotine and epibatidine) and antagonist (snake α-bungarotoxin). These hypothetical docking models offer a structural basis for rational design of drugs differentially binding to resting and active (or desensitized) conformations of the receptor site. These models thus pave the way to investigate, at the molecular level, the exciting challenge of the fast ion channel gating mechanisms by nicotinic agonists.
Keywords: nicotinic acetylcholine receptor, structure activity relationship, allosteric transitions, drug design
Current Topics in Medicinal Chemistry
Title: Rational Understanding of Nicotinic Receptors Drug Binding
Volume: 4 Issue: 6
Author(s): Thomas Grutter, Nicolas Le Novere and Jean-Pierre Changeux
Affiliation:
Keywords: nicotinic acetylcholine receptor, structure activity relationship, allosteric transitions, drug design
Abstract: The atomic determination of the acetylcholine binding protein (AChBP), a molluscan cholinergic protein, homologous to the amino-terminal extracellular domain of nicotinic receptors (nAChRs), offers opportunities for the modeling of the acetylcholine binding site and its ligands. Recently, we constructed three-dimensional models of the Nterminal part of nAChR and docked in the putative ligand-binding pocket, different agonists (acetylcholine, nicotine and epibatidine) and antagonist (snake α-bungarotoxin). These hypothetical docking models offer a structural basis for rational design of drugs differentially binding to resting and active (or desensitized) conformations of the receptor site. These models thus pave the way to investigate, at the molecular level, the exciting challenge of the fast ion channel gating mechanisms by nicotinic agonists.
Export Options
About this article
Cite this article as:
Grutter Thomas, Le Novere Nicolas and Changeux Jean-Pierre, Rational Understanding of Nicotinic Receptors Drug Binding, Current Topics in Medicinal Chemistry 2004; 4 (6) . https://dx.doi.org/10.2174/1568026043451177
DOI https://dx.doi.org/10.2174/1568026043451177 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Using Endogenous Neural Stem Cells to Enhance Recovery from Ischemic Brain Injury
Current Neurovascular Research Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets Preparation and Development of Oral Controlled Release w/o/w Multiple Emulsion of Carbamazepine
Drug Delivery Letters Genomic and Pharmacogenomic Biomarkers of Parkinson’s Disease
Current Drug Metabolism From Anreps Phenomenon to Myocardial Hypertrophy: Role of the Na+/H+ Exchanger
Current Cardiology Reviews Clinical Uses of Melatonin: Evaluation of Human Trials
Current Medicinal Chemistry Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Analysis of Progenitor Cells in the Brain before and after Treatment (Guest Editors: M.A. Curtis and L. Paulson)]
Current Pharmaceutical Biotechnology Regulatory Cascade of Neuronal Loss and Glucose Metabolism
CNS & Neurological Disorders - Drug Targets PET/MR Tomographs: A Review with Technical, Radiochemical and Clinical Perspectives
Current Radiopharmaceuticals Genetics and Molecular Biology of Tuberous Sclerosis Complex
Current Genomics Functional Connectivity in a Rat Model of Alzheimer's Disease During a Working Memory Task
Current Alzheimer Research Neuropsychiatric Involvement in Systemic Lupus Erythematosus:Current Therapeutic Approach
Current Pharmaceutical Design Current & Future Therapies of Erectile Dysfunction in Neurological Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Tau Pathology and Future Therapeutics
Current Alzheimer Research The Connections Among Autophagy, Inflammasome and Mitochondria
Current Drug Targets Central and Peripheral Pain Generators in Women with Chronic Pelvic Pain: Patient Centered Assessment and Treatment
Current Rheumatology Reviews The Development of Medications for Alcohol-Use Disorders Targeting the GABAB Receptor System
Recent Patents on CNS Drug Discovery (Discontinued) The Role of Microglial Cells on Neuroinflammation: Possible Therapeutic Applications
Recent Patents on Regenerative Medicine Nutraceuticals, A New Challenge for Medicinal Chemistry
Current Medicinal Chemistry