Abstract
The wide biochemical diversity of glycolipids in membranes explains why these molecules are often selected by pathogens (viruses, bacteria, prions) as primary sites of interactions with the cell surface. Moreover, glycolipids concentrate into cholesterol/ glycolipid-rich microdomains where they can reach high local concentrations consistent with the multivalent attachment of pathogens on the cell surface. Finally, recent studies have shown that glycolipids could also modulate protein conformation. This chaperone activity of glycolipids has been associated with various pathogenic processes including HIV infection, prion propagation, and amyloid aggregation in Alzheimers and Creutzfeldt-Jakobs diseases. Despite the potential interest for drugs mimicking glycolipid structure and function, the physicochemical properties of authentic glycolipids suggested that it might be difficult to obtain synthetic glycolipid analogues able to neutralise those pathogens before they could reach the cell surface. Recent data obtained with mono-, di-, and trihexosylceramide (GalCer, LacCer and Gb3) have proven that this was absolutely not the case and that highly active inhibitors could be designed through slight modifications of glycolipid structure. Biochemical studies of glycolipid-protein interactions have highlighted the importance of CH- π stacking interactions between galactosyl head groups of the glycolipid and aromatic amino acids of the protein. The discovery of this unique mechanism of interaction may allow a rational strategy for the design and synthesis of glycolipid-based molecules as new anti-infectious and/or anti-amyloidogenesis compounds. This strategy, which takes into account the hierarchical organisation of glycolipids into discrete membrane microdomains as well as their association with cholesterol, is discussed in the present review.
Keywords: sphingolipids, GalCer, conformation, Creutzfeldt-Jakob diseases, glycolipid-binding domain
Current Medicinal Chemistry
Title: Interaction of Proteins with Lipid Rafts Through Glycolipid-Binding Domains:Biochemical Background and Potential Therapeutic Applications
Volume: 14 Issue: 27
Author(s): Jacques Fantini
Affiliation:
Keywords: sphingolipids, GalCer, conformation, Creutzfeldt-Jakob diseases, glycolipid-binding domain
Abstract: The wide biochemical diversity of glycolipids in membranes explains why these molecules are often selected by pathogens (viruses, bacteria, prions) as primary sites of interactions with the cell surface. Moreover, glycolipids concentrate into cholesterol/ glycolipid-rich microdomains where they can reach high local concentrations consistent with the multivalent attachment of pathogens on the cell surface. Finally, recent studies have shown that glycolipids could also modulate protein conformation. This chaperone activity of glycolipids has been associated with various pathogenic processes including HIV infection, prion propagation, and amyloid aggregation in Alzheimers and Creutzfeldt-Jakobs diseases. Despite the potential interest for drugs mimicking glycolipid structure and function, the physicochemical properties of authentic glycolipids suggested that it might be difficult to obtain synthetic glycolipid analogues able to neutralise those pathogens before they could reach the cell surface. Recent data obtained with mono-, di-, and trihexosylceramide (GalCer, LacCer and Gb3) have proven that this was absolutely not the case and that highly active inhibitors could be designed through slight modifications of glycolipid structure. Biochemical studies of glycolipid-protein interactions have highlighted the importance of CH- π stacking interactions between galactosyl head groups of the glycolipid and aromatic amino acids of the protein. The discovery of this unique mechanism of interaction may allow a rational strategy for the design and synthesis of glycolipid-based molecules as new anti-infectious and/or anti-amyloidogenesis compounds. This strategy, which takes into account the hierarchical organisation of glycolipids into discrete membrane microdomains as well as their association with cholesterol, is discussed in the present review.
Export Options
About this article
Cite this article as:
Fantini Jacques, Interaction of Proteins with Lipid Rafts Through Glycolipid-Binding Domains:Biochemical Background and Potential Therapeutic Applications, Current Medicinal Chemistry 2007; 14 (27) . https://dx.doi.org/10.2174/092986707782360033
DOI https://dx.doi.org/10.2174/092986707782360033 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Transferrin and the Transferrin Receptor: Of Magic Bullets and Other Concerns
Inflammation & Allergy - Drug Targets (Discontinued) Cellular and Biochemical Actions of Melatonin which Protect Against Free Radicals: Role in Neurodegenerative Disorders
Current Neuropharmacology Plant Bioactive Peptides: Current Status and Prospects Towards Use on Human Health
Protein & Peptide Letters Cancer Immunotherapy: Battling Tumors with Gene Vaccines
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Snake Venom Proteins and Peptides as Novel Antibiotics Against Microbial Infections
Current Proteomics Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias
Current Neuropharmacology Molecule of the Month
Current Topics in Medicinal Chemistry Cancer Nanotheranostics: A Nanomedicinal Approach for Cancer Therapy and Diagnosis
Anti-Cancer Agents in Medicinal Chemistry Targeted Radiosensitization in Prostate Cancer
Current Pharmaceutical Design Therapeutic microRNA Delivery Strategies with Special Emphasis on Cancer Therapy and Tumorigenesis: Current Trends and Future Challenges
Current Drug Metabolism Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate
Current Drug Delivery Opioid Growth Factor and its Derivatives as Potential Non-toxic Multifunctional Anticancer and Analgesic Compounds
Current Medicinal Chemistry Biological Modulation by Lectins and Their Ligands in Tumor Progression and Metastasis
Anti-Cancer Agents in Medicinal Chemistry Alzheimer’s Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory ‘Wounding’ to Anti-inflammatory ‘Healing’
Current Alzheimer Research microRNAs: Small Molecules with a Potentially Role in Oral Squamous Cell Carcinoma
Current Pharmaceutical Design Cytopathological Mechanisms in Mitochondrial Disease
Current Chemical Biology Mouse Induced Glioma-Initiating Cell Models and Therapeutic Targets
Anti-Cancer Agents in Medicinal Chemistry Exploring the Role of Nerve Growth Factor in Multiple Sclerosis: Implications in Myelin Repair
CNS & Neurological Disorders - Drug Targets Ion Channels on Microglia: Therapeutic Targets for Neuroprotection
CNS & Neurological Disorders - Drug Targets Modulating Co-Stimulation During Antigen Presentation to Enhance Cancer Immunotherapy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)