Abstract
Inosine 5-monophosphate dehydrogenase (IMPDH) catalyzes the first committed step of guanosine 5-monophosphate (GMP) biosynthesis, and thus regulates the guanine nucleotide pool, which in turn governs proliferation. Human IMPDHs are validated targets for immunosuppressive, antiviral and anticancer drugs, but as yet microbial IMPDHs have not been exploited in antimicrobial chemotherapy. Selective inhibitors of IMPDH from Cryptosporidium parvum have recently been discovered that display anti-parasitic activity in cell culture models of infection. X-ray crystal structure and mutagenesis experiments identified the structural features that determine inhibitor susceptibility. These features are found in IMPDHs from a wide variety of pathogenic bacteria, including select agents and multiply drug resistant strains. A second generation inhibitor displays antibacterial activity against Helicobacter pylori, demonstrating the antibiotic potential of IMPDH inhibitors.
Keywords: Antibacterial, Cryptosporidium parvum, guanine nucleotide, biosynthesis, Helicobacter pylori, IMPDH, inosine 5'- monophosphate dehydrogenase, select agents, Mycobacterium tuberculosis
Current Medicinal Chemistry
Title: The Antibiotic Potential of Prokaryotic IMP Dehydrogenase Inhibitors
Volume: 18 Issue: 13
Author(s): L. Hedstrom, G. Liechti, J. B. Goldberg and D. R. Gollapalli
Affiliation:
Keywords: Antibacterial, Cryptosporidium parvum, guanine nucleotide, biosynthesis, Helicobacter pylori, IMPDH, inosine 5'- monophosphate dehydrogenase, select agents, Mycobacterium tuberculosis
Abstract: Inosine 5-monophosphate dehydrogenase (IMPDH) catalyzes the first committed step of guanosine 5-monophosphate (GMP) biosynthesis, and thus regulates the guanine nucleotide pool, which in turn governs proliferation. Human IMPDHs are validated targets for immunosuppressive, antiviral and anticancer drugs, but as yet microbial IMPDHs have not been exploited in antimicrobial chemotherapy. Selective inhibitors of IMPDH from Cryptosporidium parvum have recently been discovered that display anti-parasitic activity in cell culture models of infection. X-ray crystal structure and mutagenesis experiments identified the structural features that determine inhibitor susceptibility. These features are found in IMPDHs from a wide variety of pathogenic bacteria, including select agents and multiply drug resistant strains. A second generation inhibitor displays antibacterial activity against Helicobacter pylori, demonstrating the antibiotic potential of IMPDH inhibitors.
Export Options
About this article
Cite this article as:
Hedstrom L., Liechti G., B. Goldberg J. and R. Gollapalli D., The Antibiotic Potential of Prokaryotic IMP Dehydrogenase Inhibitors, Current Medicinal Chemistry 2011; 18 (13) . https://dx.doi.org/10.2174/092986711795590129
DOI https://dx.doi.org/10.2174/092986711795590129 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Nanoemulsion for the Effective Treatment and Management of Anti-tubercular Drug Therapy
Recent Patents on Anti-Infective Drug Discovery Metals and Parkinson's Disease: Mechanisms and Biochemical Processes
Current Medicinal Chemistry Syphilis and HIV Co-Infection: When is Lumbar Puncture Indicated?
Current HIV Research Meta-analysis Identifies Tumor Necrosis Factor-alpha and Interleukin-1 beta as Diagnostic Biomarkers for Bacterial and Aseptic Meningitis
Current Neurovascular Research Bladder Cancer: A Simple Model Becomes Complex
Current Genomics COX-2 in Brain and Spinal Cord - Implications for Therapeutic Use.
Current Medicinal Chemistry A New Binding Site Involving the C-terminal Domain to Design Specific Inhibitors of PepX
Protein & Peptide Letters subject Index To Volume 1
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Allopurinol Hypersensitivity Reactions: Desensitization Strategies and New Therapeutic Alternative Molecules
Inflammation & Allergy - Drug Targets (Discontinued) Aβ Oligomers Induce Glutamate Release from Hippocampal Neurons
Current Alzheimer Research Current Approaches for New TB Drugs
Current Respiratory Medicine Reviews A Review of the Potential Receptors of Migraine with a Special Emphasis on CGRP to Develop an Ideal Antimigraine Drug
Current Molecular Pharmacology The Role of Glutamate and its Receptors in Migraine
CNS & Neurological Disorders - Drug Targets Structure Based Virtual Screening for the Identification of Potential Inhibitors for Penicillin Binding Protein 2B of the Resistant 5204 Strain of <i>Streptococcus pneumoniae</i>
Current Bioinformatics Syphilis: An Epidemiological Review
Current Women`s Health Reviews Neuroprotection and Hypothermia in Infants and Children
Current Drug Targets Gene and Cancer Therapy - Pseudorabies Virus: A Novel Research and Therapeutic Tool?
Current Gene Therapy Blood-brain Barrier Drug Discovery for Central Nervous System Infections
Current Drug Targets - Infectious Disorders Pleiotropic Effects of Nitric Oxide on SARS-CoV-2 Infections
Coronaviruses Rationale for Peptide and DNA Based Epitope Vaccines for Alzheimers Disease Immunotherapy
CNS & Neurological Disorders - Drug Targets