![conference banner](/images/conference-banner.jpeg)
Abstract
A major neurotransmitter, L-Glutamate must be stored, transported and received, and these processes are mediated by proteins that bind this simple yet essential amino acid. Detailed evidence continues to emerge on the structure of Glu binding proteins, which includes both receptors and transporters. It appears that receptors and transporters bind to Glu in different conformations, which may present a pharmacological opportunity. This review will compare and contrast information available on Glu Receptors (AMPA, NMDA, KA and mGlu), excitatory amino acid transporters (EAATs), the system Xc- transporter (XCT) and the vesicular Glutamate transporter (GVT). The cross-reactivity of ligands which have been previously used to characterize the glutamate binding proteins with system Xc- raises some fundamental interpretational issues regarding the mechanisms through which these analogues produce CNS damage. Although at one time it was thought that unraveling selectivity among glutamate binding proteins was an intractable problem, recently the NMDA antagonist (memantine) has been approved for general medical practice for treatment of Alzheimers disease. Two other agents are in advanced clinical trials: an Ampakine for potential improvement of cognitive disorders, and a selective mGlu agonist for treatment of anxiety. The prospects for unraveling cross-reactivity will be weighed in light of a critical comparison of the glutamate binding protein targets.
Keywords: Glutamate, receptor, transporter, ligand, inhibitor, substrate, isoxazole
Current Topics in Medicinal Chemistry
Title: Can Selective Ligands for Glutamate Binding Proteins be Rationally Designed?
Volume: 6 Issue: 8
Author(s): Nicholas R. Natale, Kathy R. Magnusson and Jared K. Nelson
Affiliation:
Keywords: Glutamate, receptor, transporter, ligand, inhibitor, substrate, isoxazole
Abstract: A major neurotransmitter, L-Glutamate must be stored, transported and received, and these processes are mediated by proteins that bind this simple yet essential amino acid. Detailed evidence continues to emerge on the structure of Glu binding proteins, which includes both receptors and transporters. It appears that receptors and transporters bind to Glu in different conformations, which may present a pharmacological opportunity. This review will compare and contrast information available on Glu Receptors (AMPA, NMDA, KA and mGlu), excitatory amino acid transporters (EAATs), the system Xc- transporter (XCT) and the vesicular Glutamate transporter (GVT). The cross-reactivity of ligands which have been previously used to characterize the glutamate binding proteins with system Xc- raises some fundamental interpretational issues regarding the mechanisms through which these analogues produce CNS damage. Although at one time it was thought that unraveling selectivity among glutamate binding proteins was an intractable problem, recently the NMDA antagonist (memantine) has been approved for general medical practice for treatment of Alzheimers disease. Two other agents are in advanced clinical trials: an Ampakine for potential improvement of cognitive disorders, and a selective mGlu agonist for treatment of anxiety. The prospects for unraveling cross-reactivity will be weighed in light of a critical comparison of the glutamate binding protein targets.
Export Options
About this article
Cite this article as:
Natale R. Nicholas, Magnusson R. Kathy and Nelson K. Jared, Can Selective Ligands for Glutamate Binding Proteins be Rationally Designed?, Current Topics in Medicinal Chemistry 2006; 6 (8) . https://dx.doi.org/10.2174/156802606777057535
DOI https://dx.doi.org/10.2174/156802606777057535 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Comparison of Two Naloxone Regimens in Opioid-dependent Methadoneoverdosed Patients: A Clinical Trial Study
Current Clinical Pharmacology Beyond the Reproductive Effect of Sex Steroids: Their Role During Immunity to Helminth Parasite Infections
Mini-Reviews in Medicinal Chemistry Inhibitors of c-jun-N-Terminal Kinase (JNK)
Mini-Reviews in Medicinal Chemistry Tau-Focused Immunotherapy for Alzheimers Disease and Related Tauopathies
Current Alzheimer Research Further Vitamin D Analogs
Current Vascular Pharmacology Biomarkers Associated with Stroke Risk in Atrial Fibrillation
Current Medicinal Chemistry Clozapine Safety, 35 Years Later
Current Drug Safety Matrix Metalloproteinases: New Routes to the Use of MT1-MMP As A Therapeutic Target in Angiogenesis-Related Disease
Current Pharmaceutical Design Heart Rate as a Therapeutic Target in Angina Pectoris
Current Pharmaceutical Design New Targets for Treating the Underlying Pathophysiology and Nonmotor Aspects of Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Novel Concepts in the Development of Platinum Antitumor Drugs
Current Medicinal Chemistry - Anti-Cancer Agents Validated Microemulsion Liquid Chromatography-Fluorescence Method for the Quantification of Duloxetine and its Two Main Metabolites in Plasma: Application to Clinical Pharmacokinetic Studies
Current Pharmaceutical Analysis Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance
Current Cardiology Reviews Nutritional Overview on the Management of Type 2 Diabetes and the Prevention of its Complications
Current Diabetes Reviews Risk Factors for Suicidal Ideation Among High School Students in Istanbul
Adolescent Psychiatry Advances in the Treatment of Neurodegenerative Disorders Employing Nanoparticles
Recent Patents on Drug Delivery & Formulation The Role of Estradiol and Progesterone in Mucosal HIV-1 Infection, Transmission and Pathogenesis
Current Women`s Health Reviews Cross-Interplay between Osmolytes and mTOR in Alzheimer's Disease Pathogenesis
Current Pharmaceutical Design Neutrophils as Sentinel Cells of the Immune System: A Role of the MPO-halide-system in Innate and Adaptive Immunity
Current Medicinal Chemistry Ag+ Complexes as Potential Therapeutic Agents in Medicine and Pharmacy
Current Medicinal Chemistry