Abstract
DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a type II C-type lectin that functions as an adhesion molecule located on dendritic cells (DCs). It enables some of the functions of DCs, including migration, pathogen recognition, internalisation and processing, and their binding to T cells. HIV-1 has been reported to enter DCs by being bound to DC-SIGN, escaping the normal lytic pathway in DCs endosomes and avoiding the immune system defence system. A very similar mechanism of survival has been observed for some other pathogens. This makes DC-SIGN a receptor of interest in the design of distinctive anti-infectives that would inhibit DC-SIGN-pathogen interaction by blocking the very first step in pathogen infection. In this review we outline the development of DC-SIGN antagonists, focusing mainly on a glycomimetic approach. Based on the fact that DCSIGN binds mannose- and fucose-based oligo- and polysaccharides, their structural mimics have been designed and proved to inhibit pathogen-DC-SIGN interaction. Furthermore, recent in vitro studies have demonstrated that DC-SIGN antagonists block effectively the transmission of pathogens like HIV-1 and Ebola to CD4+ T cells. Although DC-SIGN has not been validated in vivo as a druggable target yet, we await future DC-SIGN antagonists as a new and highly promising group of novel anti-infectives.
Keywords: DC-SIGN antagonists, anti-infectives, glycomimetics, dendrimers, dendrons, DC-SIGN, C-type lectin, dendritic cells, pathogenrecognition receptor, HIV-1
Current Medicinal Chemistry
Title: DC-SIGN Antagonists, a Potential New Class of Anti-Infectives
Volume: 19 Issue: 7
Author(s): M. Anderluh, G. Jug, U. Svajger and N. Obermajer
Affiliation:
Keywords: DC-SIGN antagonists, anti-infectives, glycomimetics, dendrimers, dendrons, DC-SIGN, C-type lectin, dendritic cells, pathogenrecognition receptor, HIV-1
Abstract: DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a type II C-type lectin that functions as an adhesion molecule located on dendritic cells (DCs). It enables some of the functions of DCs, including migration, pathogen recognition, internalisation and processing, and their binding to T cells. HIV-1 has been reported to enter DCs by being bound to DC-SIGN, escaping the normal lytic pathway in DCs endosomes and avoiding the immune system defence system. A very similar mechanism of survival has been observed for some other pathogens. This makes DC-SIGN a receptor of interest in the design of distinctive anti-infectives that would inhibit DC-SIGN-pathogen interaction by blocking the very first step in pathogen infection. In this review we outline the development of DC-SIGN antagonists, focusing mainly on a glycomimetic approach. Based on the fact that DCSIGN binds mannose- and fucose-based oligo- and polysaccharides, their structural mimics have been designed and proved to inhibit pathogen-DC-SIGN interaction. Furthermore, recent in vitro studies have demonstrated that DC-SIGN antagonists block effectively the transmission of pathogens like HIV-1 and Ebola to CD4+ T cells. Although DC-SIGN has not been validated in vivo as a druggable target yet, we await future DC-SIGN antagonists as a new and highly promising group of novel anti-infectives.
Export Options
About this article
Cite this article as:
Anderluh M., Jug G., Svajger U. and Obermajer N., DC-SIGN Antagonists, a Potential New Class of Anti-Infectives, Current Medicinal Chemistry 2012; 19 (7) . https://dx.doi.org/10.2174/092986712799320664
DOI https://dx.doi.org/10.2174/092986712799320664 |
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
-
S-nitrosation/Denitrosation in Cardiovascular Pathologies: Facts and Concepts for the Rational Design of S-nitrosothiols
Current Pharmaceutical Design Designing and Testing New Therapeutic Modalities for Treatment of Inflammatory Bowel Disease: Role of Experimental Animal Models
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Pollen Enigma: Modulation of the Allergic Immune Response by Non-Allergenic, Pollen-Derived Compounds
Current Pharmaceutical Design Natural Carriers for siRNA Delivery
Current Pharmaceutical Design Selective Inhibitors of Inducible Nitric Oxide Synthase: Potential Agents for the Treatment of Inflammatory Diseases?
Current Topics in Medicinal Chemistry Peroxisome Proliferator-Activated Receptor γ Agonists as Insulin Sensitizers: From the Discovery to Recent Progress
Current Topics in Medicinal Chemistry Survivin: Role in Normal Cells and in Pathological Conditions
Current Cancer Drug Targets Fatty Acids - Induced Lipotoxicity and Inflammation
Current Drug Metabolism Anti-TNF Antibodies in Inflammatory Bowel Disease: Do We Finally Know How it Works?
Current Drug Targets Quantitative Structure-Activity Relationship Studies: Understanding the Mechanism of Tyrosine Kinase Inhibition
Current Enzyme Inhibition Systematic and Pairwise Analysis of the Effects of Aromatic Halogenation and Trifluoromethyl Substitution on Human Liver Microsomal Clearance
Drug Metabolism Letters Redox-inactive Analogue of Tocotrienol as a Potential Anti-cancer Agent
Anti-Cancer Agents in Medicinal Chemistry Quantification of Angiogenesis and Lymphangiogenesis in the Dual ex vivo Aortic and Thoracic Duct Assay
Protein & Peptide Letters Age-Related Changes and Effects of Mild Hypothermia on Carotid Artery Reactivity in Newborn Rats
CNS & Neurological Disorders - Drug Targets The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment
Current Medicinal Chemistry Notch Inhibitors as a New Tool in the War on Cancer: A Pathway to Watch
Current Pharmaceutical Biotechnology Aminoglycosidic Aminocyclitol Antibiotics-A Wonder, But Toxic Drugs:Developments and Clinical Implications
Anti-Infective Agents in Medicinal Chemistry Is There a Role for Antioxidants in the Prevention of Infection-Associated Carcinogenesis and in the Treatment of Infection-Driven Tumors?
Current Topics in Medicinal Chemistry Laser Modified Phenothiazines and Hydantoins: Photo-products Characterisation and Application on Animal Eyes Pseudo-tumours
Letters in Drug Design & Discovery Predicting Pediatric Drug Disposition-Present and Future Directions of Pediatric Physiologically-Based Pharmacokinetics
Drug Metabolism Letters