Abstract
Tuberculosis is still a leading cause of death in developing countries and a resurgent disease in developed countries. The selection and soaring spread of Mycobacterium tuberculosis multidrug-resistant (MDR-TB) and extensively drug-resistant strains (XDR-TB) is a severe public health problem. Currently, there is an urgent need of new drugs for tuberculosis treatment, with novel mechanisms of action and, moreover, the necessity to identify new drug targets. Several enzymes involved in various metabolic processes have been described as potential targets for the development of new drugs. Recently, two different classes of most promising drugs, the benzothiazinones (BTZ) and the dinitrobenzamide derivatives (DNB), have been found to be highly active against M. tuberculosis, including XDR-TB strains. Interestingly, both drugs have the sametarget: the heteromeric decaprenylphosphoryl-β-D-ribose 2-epimerase encoded by dprE1 (Rv3790) and dprE2 (Rv3791) genes, respectively. DprE1 and DprE2 are involved in the biosynthesis of D-arabinose and, in particular, they are essential to perform the transformation of decaprenylphosphoryl-D-ribose to decaprenylphosphoryl-D-arabinose, which is a substrate for arabinosyltransferases in the synthesis of the cell-envelope arabinogalactan and liporabinomannan polysaccharides of mycobacteria. Arabinogalactan is a fundamental component of the mycobacterial cell wall, which covalently binds the outer layer of mycolic acids to peptidoglycan. The heteromeric decaprenylphosphoryl-β-D-ribose 2-epimerase thus represents a valid vulnerable antimycobacterial drug target which could result “magic” for tuberculosis treatment.
Keywords: Mycobacterium tuberculosis, Rv3790 (DprE1), cellular target, cell wall, new drugs
Current Medicinal Chemistry
Title: Decaprenylphosphoryl-β-D-Ribose 2-Epimerase from Mycobacterium tuberculosis is a Magic Drug Target
Volume: 17 Issue: 27
Author(s): G. Manina, M. R. Pasca, S. Buroni, E. De Rossi and G. Riccardi
Affiliation:
Keywords: Mycobacterium tuberculosis, Rv3790 (DprE1), cellular target, cell wall, new drugs
Abstract: Tuberculosis is still a leading cause of death in developing countries and a resurgent disease in developed countries. The selection and soaring spread of Mycobacterium tuberculosis multidrug-resistant (MDR-TB) and extensively drug-resistant strains (XDR-TB) is a severe public health problem. Currently, there is an urgent need of new drugs for tuberculosis treatment, with novel mechanisms of action and, moreover, the necessity to identify new drug targets. Several enzymes involved in various metabolic processes have been described as potential targets for the development of new drugs. Recently, two different classes of most promising drugs, the benzothiazinones (BTZ) and the dinitrobenzamide derivatives (DNB), have been found to be highly active against M. tuberculosis, including XDR-TB strains. Interestingly, both drugs have the sametarget: the heteromeric decaprenylphosphoryl-β-D-ribose 2-epimerase encoded by dprE1 (Rv3790) and dprE2 (Rv3791) genes, respectively. DprE1 and DprE2 are involved in the biosynthesis of D-arabinose and, in particular, they are essential to perform the transformation of decaprenylphosphoryl-D-ribose to decaprenylphosphoryl-D-arabinose, which is a substrate for arabinosyltransferases in the synthesis of the cell-envelope arabinogalactan and liporabinomannan polysaccharides of mycobacteria. Arabinogalactan is a fundamental component of the mycobacterial cell wall, which covalently binds the outer layer of mycolic acids to peptidoglycan. The heteromeric decaprenylphosphoryl-β-D-ribose 2-epimerase thus represents a valid vulnerable antimycobacterial drug target which could result “magic” for tuberculosis treatment.
Export Options
About this article
Cite this article as:
Manina G., R. Pasca M., Buroni S., De Rossi E. and Riccardi G., Decaprenylphosphoryl-β-D-Ribose 2-Epimerase from Mycobacterium tuberculosis is a Magic Drug Target, Current Medicinal Chemistry 2010; 17 (27) . https://dx.doi.org/10.2174/092986710791959693
DOI https://dx.doi.org/10.2174/092986710791959693 |
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
-
Diagnostic Accuracy of Monocyte Chemotactic Protein (MCP)-2 as Biomarker in Response to PE35/PPE68 Proteins: A Promising Diagnostic Method for the Discrimination of Active and Latent Tuberculosis
Protein & Peptide Letters Synthesis of 3-(7-Methylbenzo[d]oxazol-4-yl) Butanoic Acid: A Precursor of (+)-seco-Pseudopteroxazole and (+)-Pseudopteroxazole
Letters in Organic Chemistry Advances of Inorganic Materials in the Detection and Therapeutic Uses against Coronaviruses
Current Medicinal Chemistry Structure and Function of Enzymes of Shikimate Pathway
Current Bioinformatics Genetics and Vaccines in the Era of Personalized Medicine
Current Genomics Pediatric Immune Dysfunction and Health Risks Following Early-Life Immune Insult
Current Pediatric Reviews Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop
Current HIV Research Editorial [Hot Topic: Looking Beyond the Obvious: Search for Novel Targets and Drugs for Reducing the Burden of Infectious Diseases (Guest Editor: Neelima Arora)]
Mini-Reviews in Medicinal Chemistry Evaluation of Brazilian Biotechnology Patent Activity from 1975 to 2010
Recent Patents on DNA & Gene Sequences Meet Our Editorial Board Member
Current Drug Discovery Technologies Drug Targeting Strategies for Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Multi-Drug Resistant Pulmonary Tuberculosis
Current Respiratory Medicine Reviews HIV-Tuberculous Meningitis Co-Infection: A Systematic Review and Meta-Analysis
Current Pharmaceutical Biotechnology Chemical and Medicinal Versatility of Substituted 1,4-Dihydropyridines
Current Bioactive Compounds Nano-antimicrobials: A New Paradigm for Combating Mycobacterial Resistance
Current Pharmaceutical Design Microbial Immune Evasion Employing Suppressor of Cytokine Signaling (SOCS) Proteins
Inflammation & Allergy - Drug Targets (Discontinued) Novel Approach for the Synthesis of Pyrrolo[2,1-c][1,4]Benzoxazines and Pyrrolo[1,2-a]Quinoxalines
Combinatorial Chemistry & High Throughput Screening Meet Our Editorial Board Member
Combinatorial Chemistry & High Throughput Screening Anomalous Vascular Supply of Bronchial Circulation in Cystic Fibrosis Patients with Massive Hemoptysis
Current Respiratory Medicine Reviews 1,2,5-Thiadiazole Scaffold: A Review on Recent Progress in Biological Activities
Combinatorial Chemistry & High Throughput Screening