Abstract
There is an urgent need for the design and development of new and selective drugs for the treatment of malaria and bacterial infections as these pathogens are developing resistance to presently available therapies. Malaria is a life threatening disease in many countries and responsible for almost one million deaths annually. In particular, drug-resistant malarial parasites are hindering effective control of malaria and prompting to find novel druggable targets and develop compounds with mechanism of action different from the conventional drugs. In this quest, efforts were made to determine three-dimensional structures of Plasmodium falciparum and Plasmodium vivax FK506 binding proteins which bind the macrolides (FK506 and rapamycin) and also demonstrate peptidylprolyl cis-trans isomerase activity in a similar manner as human FKBP12. Previous studies revealed that the immunosuppressive drug FK506 exhibits potential anti-malarial activity by binding FK506 binding domains (FKBD). This review focuses on three different types of FK506 binding proteins/domains in pathogens, their structural characteristics and biological roles. Binding ability of these proteins with the macrolides has opened new possibilities to develop selective inhibitors for these novel targets to combat the life threatening infections.
Keywords: FK506, rapamycin, FKBP35, Plasmodium, malaria, bacterial infections, FK506 binding domain, eukaryotic cells, pathogens, FKBP12
Current Medicinal Chemistry
Title: Targeting FK506 Binding Proteins to Fight Malarial and Bacterial Infections:Current Advances and Future Perspectives
Volume: 18 Issue: 12
Author(s): N. Bharatham, M. W. Chang and H. S. Yoon
Affiliation:
Keywords: FK506, rapamycin, FKBP35, Plasmodium, malaria, bacterial infections, FK506 binding domain, eukaryotic cells, pathogens, FKBP12
Abstract: There is an urgent need for the design and development of new and selective drugs for the treatment of malaria and bacterial infections as these pathogens are developing resistance to presently available therapies. Malaria is a life threatening disease in many countries and responsible for almost one million deaths annually. In particular, drug-resistant malarial parasites are hindering effective control of malaria and prompting to find novel druggable targets and develop compounds with mechanism of action different from the conventional drugs. In this quest, efforts were made to determine three-dimensional structures of Plasmodium falciparum and Plasmodium vivax FK506 binding proteins which bind the macrolides (FK506 and rapamycin) and also demonstrate peptidylprolyl cis-trans isomerase activity in a similar manner as human FKBP12. Previous studies revealed that the immunosuppressive drug FK506 exhibits potential anti-malarial activity by binding FK506 binding domains (FKBD). This review focuses on three different types of FK506 binding proteins/domains in pathogens, their structural characteristics and biological roles. Binding ability of these proteins with the macrolides has opened new possibilities to develop selective inhibitors for these novel targets to combat the life threatening infections.
Export Options
About this article
Cite this article as:
Bharatham N., W. Chang M. and S. Yoon H., Targeting FK506 Binding Proteins to Fight Malarial and Bacterial Infections:Current Advances and Future Perspectives, Current Medicinal Chemistry 2011; 18 (12) . https://dx.doi.org/10.2174/092986711795496818
DOI https://dx.doi.org/10.2174/092986711795496818 |
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
-
The Efficacy of Viral Capsid Inhibitors in Human Enterovirus Infection and Associated Diseases
Current Medicinal Chemistry The Methylerythritol Phosphate Pathway and its Significance as a Novel Drug Target
Current Pharmaceutical Biotechnology Dendritic Cells and Macrophages: Same Receptors but Different Functions
Current Immunology Reviews (Discontinued) Daptomycin: A Review of Properties, Clinical Use, Drug Delivery and Resistance
Mini-Reviews in Medicinal Chemistry Tuberculosis Vaccines: Hopes and Hurdles
Infectious Disorders - Drug Targets Outcome Prediction after Non-aneurysmal Non-traumatic Subarachnoid Hemorrhage
Current Neurovascular Research Nasal Drug Delivery System-Factors Affecting and Applications
Current Drug Therapy Isoflurane Facilitates Synaptic NMDA Receptor Endocytosis in Mice Primary Neurons
Current Molecular Medicine Intracranial Non-traumatic Aneurysms in Children and Adolescents
Current Pediatric Reviews Diagnosis of Systemic Lupus Erythematosus in an Unusual Presentation: What a Primary Care Physician Should Know
Current Rheumatology Reviews Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole
Current Drug Metabolism The Role of CD8+ T Cells in Multiple Sclerosis and its Animal Models
Current Drug Targets - Inflammation & Allergy Active Metabolites Resulting from Decarboxylation, Reduction and Ester Hydrolysis of Parent Drugs
Current Drug Metabolism Cancer Metastasis: Characterization and Identification of the Behavior of Metastatic Tumor Cells and the Cell Adhesion Molecules, including Carbohydrates
Current Drug Targets - Cardiovascular & Hematological Disorders The Role of Melatonin in Multiple Sclerosis, Huntington's Disease and Cerebral Ischemia
CNS & Neurological Disorders - Drug Targets Minocycline and Doxycycline: More Than Antibiotics
Current Molecular Pharmacology Pathogenesis and Immune Status in COVID-19 Pneumonia - A Minireview
Coronaviruses Activin-A: A New Piece in the Puzzle of Tolerance in Asthma
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) Proinflammatory Cytokines and Chemokines in Neonatal Brain Damage
Current Pediatric Reviews JNK Signalling: A Possible Target to Prevent Neurodegeneration
Current Pharmaceutical Design