Abstract
A variety of anti-proliferative drugs is based on the structure of purine or pyrimidine nucleosides. These compounds, after phosphorylation, act as analogs of natural nucleotides. In vivo they are recognized by enzymes that transform them either into anti-metabolites targeted to the synthesis of DNA or RNA, or to inactive products of detoxification. 5'-Nucleotidases of different specificity and cellular localization can either remove the phosphate residue from the 5'- position of (deoxy)nucleotide or transfer it from nucleoside monophosphate onto other nucleosides. Such a nucleoside phosphotransferase activity also works with analogs of canonical nucleotides and nucleosides. The majority of nucleoside analogs is metabolized by intracellular cytoplasmic or mitochondrial 5'-nucleotidases and only few reactions proceed on the cell surface. This review summarizes our knowledge of cytoplasmic and mitochondrial forms of 5'-nucleotidases and focuses on their ability to dephosphorylate different analogs of canonical nucleoside 5'-monophosphates. The involvement of 5'-nucleotidases in the phosphotransfer reaction with some nucleoside analogs has been also presented. The importance of the reactions catalyzed by 5'-nucleotidases in clinical resistance to nucleoside-based drugs used in the treatment of cancer or viral diseases, as well as in activation of pro-drugs has been highlighted
Keywords: 5'-nucleotidase, nucleoside analogs, nucleotide metabolism, drug resistance.
Current Medicinal Chemistry
Title:The Role of Soluble 5'-Nucleotidases in the Conversion of Nucleotide Analogs: Metabolic and Therapeutic Aspects
Volume: 20 Issue: 34
Author(s): A. C. Składanowski
Affiliation:
Keywords: 5'-nucleotidase, nucleoside analogs, nucleotide metabolism, drug resistance.
Abstract: A variety of anti-proliferative drugs is based on the structure of purine or pyrimidine nucleosides. These compounds, after phosphorylation, act as analogs of natural nucleotides. In vivo they are recognized by enzymes that transform them either into anti-metabolites targeted to the synthesis of DNA or RNA, or to inactive products of detoxification. 5'-Nucleotidases of different specificity and cellular localization can either remove the phosphate residue from the 5'- position of (deoxy)nucleotide or transfer it from nucleoside monophosphate onto other nucleosides. Such a nucleoside phosphotransferase activity also works with analogs of canonical nucleotides and nucleosides. The majority of nucleoside analogs is metabolized by intracellular cytoplasmic or mitochondrial 5'-nucleotidases and only few reactions proceed on the cell surface. This review summarizes our knowledge of cytoplasmic and mitochondrial forms of 5'-nucleotidases and focuses on their ability to dephosphorylate different analogs of canonical nucleoside 5'-monophosphates. The involvement of 5'-nucleotidases in the phosphotransfer reaction with some nucleoside analogs has been also presented. The importance of the reactions catalyzed by 5'-nucleotidases in clinical resistance to nucleoside-based drugs used in the treatment of cancer or viral diseases, as well as in activation of pro-drugs has been highlighted
Export Options
About this article
Cite this article as:
Składanowski C. A., The Role of Soluble 5'-Nucleotidases in the Conversion of Nucleotide Analogs: Metabolic and Therapeutic Aspects, Current Medicinal Chemistry 2013; 20 (34) . https://dx.doi.org/10.2174/0929867311320340005
DOI https://dx.doi.org/10.2174/0929867311320340005 |
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
-
Modulation of Antibiotic Efflux in Bacteria
Current Medicinal Chemistry - Anti-Infective Agents Therapeutic Proteins in Tumors and Targeted Therapeutic Agents for Cancer Patients
Protein & Peptide Letters An Integrative Informatics Approach to Explain the Mechanism of Action of N1-(Anthraquinon-2-yl) Amidrazones as BCR/ABL Inhibitors
Current Computer-Aided Drug Design Novel Inhibitors of Inosine Monophosphate Dehydrogenase in Patent Literature of the Last Decade
Recent Patents on Anti-Cancer Drug Discovery Inhibitors of Cyclin Dependent Kinases: Useful Targets for Cancer Treatment
Current Cancer Drug Targets Development of Patents and Clinical Trials on Regenerative Therapy: Gene Therapy
Recent Patents on Regenerative Medicine 4-aryl/heteroaryl-4H-fused Pyrans as Anti-proliferative Agents: Design, Synthesis and Biological Evaluation
Anti-Cancer Agents in Medicinal Chemistry Enhancing the Cytotoxic Activity of Novel Targeted Therapies – Is There a Role for a Combinatorial Approach?
Current Clinical Pharmacology 3-Hydroxy-2-phenyl-4(1H)-quinolinones as Promising Biologically Active Compounds
Mini-Reviews in Medicinal Chemistry Editorial (Thematic Issue: Unlocking the Potential of Stem Cells in Cell Therapy, Drug Delivery and Drug Discovery)
Current Drug Delivery Iron Chelators: Development of Novel Compounds with High and Selective Anti-Tumour Activity
Current Drug Delivery The Impact of CRISPR/Cas9-Based Genomic Engineering on Biomedical Research and Medicine
Current Molecular Medicine Platinum-Based Agents for Individualized Cancer Treatment
Current Molecular Medicine Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation
Current Pharmaceutical Design An Overview of Notch Signaling in Adult Tissue Renewal and Maintenance
Current Alzheimer Research Intriguing Classes of Acridine Derivatives as DNA-binding Antitumour Agents: From Pyrimido[5,6,1-de]acridines to Bis(acridine-4-carboxamides)
Medicinal Chemistry Reviews - Online (Discontinued) siRNA-Mediated Knock-Down of P-Glycoprotein Expression Reveals Distinct Cellular Disposition of Anticancer Tyrosine Kinases Inhibitors
Drug Metabolism Letters Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Interferon Treatment in Patients with Hypereosinophilia
Current Drug Targets