Abstract
Background: Nucleoside phosphorylases catalyze the reversible phosphorolysis of pyrimidine and purine nucleosides in the presence of phosphate. They are relevant to the appropriate function of the immune system in mammals and interesting drug targets for cancer treatment. Next to their role as drug targets nucleoside phosphorylases are used as catalysts in the synthesis of nucleosides and their analogs that are widely applied as pharmaceuticals.
Methods: Based on their substrates nucleoside phosphorylases are classified as pyrimidine and purine nucleoside phosphorylases. This article describes the substrate spectra of nucleoside phosphorylases and structural properties that influence their activity. Substrate ranges are summarized and relations between members of pyrimidine or purine nucleoside phosphorylases are elucidated.
Results: Nucleoside phosphorylases accept a broad spectrum of substrates: they accept both base and sugar modified nucleosides. The most widely studied nucleoside phosphorylases are those of Escherichia coli, mammals and pathogens. However, recently the attention has been shifted to thermophilic nucleoside phosphorylases due to several advantages. Nucleoside phosphorylases have been applied to produce drugs like ribavirin or fludarabine. However, limitations were observed when drugs show an open ring structure. Site-directed mutagenesis approaches were shown to alter the substrate specificity of nucleoside phosphorylases.
Conclusion: Nucleoside phosphorylases are valuable tools to produce modified nucleosides with therapeutic or diagnostic potential with high affinity and specificity. A wide variety of nucleoside phosphorylases are available in nature which differ in their protein sequence and show varying substrate spectra. To overcome limitations of the naturally occurring enzymes site-directed mutagenesis approaches can be used.
Keywords: Nucleoside phosphorylase, pyrimidine analog, purine analog, catalytic mechanism, structure, function, mutagensesis.
Current Pharmaceutical Design
Title:Substrate Spectra of Nucleoside Phosphorylases and their Potential in the Production of Pharmaceutically Active Compounds
Volume: 23 Issue: 45
Author(s): Heba Yehia, Sarah Kamel, Katharina Paulick, Peter Neubauer and Anke Wagner*
Affiliation:
- TU Berlin, Institute of Biotechnology, Department of Bioprocess Engineering, Ackerstr. 76, 13355 Berlin,Germany
Keywords: Nucleoside phosphorylase, pyrimidine analog, purine analog, catalytic mechanism, structure, function, mutagensesis.
Abstract: Background: Nucleoside phosphorylases catalyze the reversible phosphorolysis of pyrimidine and purine nucleosides in the presence of phosphate. They are relevant to the appropriate function of the immune system in mammals and interesting drug targets for cancer treatment. Next to their role as drug targets nucleoside phosphorylases are used as catalysts in the synthesis of nucleosides and their analogs that are widely applied as pharmaceuticals.
Methods: Based on their substrates nucleoside phosphorylases are classified as pyrimidine and purine nucleoside phosphorylases. This article describes the substrate spectra of nucleoside phosphorylases and structural properties that influence their activity. Substrate ranges are summarized and relations between members of pyrimidine or purine nucleoside phosphorylases are elucidated.
Results: Nucleoside phosphorylases accept a broad spectrum of substrates: they accept both base and sugar modified nucleosides. The most widely studied nucleoside phosphorylases are those of Escherichia coli, mammals and pathogens. However, recently the attention has been shifted to thermophilic nucleoside phosphorylases due to several advantages. Nucleoside phosphorylases have been applied to produce drugs like ribavirin or fludarabine. However, limitations were observed when drugs show an open ring structure. Site-directed mutagenesis approaches were shown to alter the substrate specificity of nucleoside phosphorylases.
Conclusion: Nucleoside phosphorylases are valuable tools to produce modified nucleosides with therapeutic or diagnostic potential with high affinity and specificity. A wide variety of nucleoside phosphorylases are available in nature which differ in their protein sequence and show varying substrate spectra. To overcome limitations of the naturally occurring enzymes site-directed mutagenesis approaches can be used.
Export Options
About this article
Cite this article as:
Yehia Heba, Kamel Sarah , Paulick Katharina, Neubauer Peter and Wagner Anke*, Substrate Spectra of Nucleoside Phosphorylases and their Potential in the Production of Pharmaceutically Active Compounds, Current Pharmaceutical Design 2017; 23 (45) . https://dx.doi.org/10.2174/1381612823666171024155811
DOI https://dx.doi.org/10.2174/1381612823666171024155811 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Antiviral Properties of Quinolone-based Drugs
Current Drug Targets - Infectious Disorders Inhibitors of Lactate Dehydrogenase Isoforms and their Therapeutic Potentials
Current Medicinal Chemistry Proteomic Classification of Breast Cancer
Current Drug Targets Recent Developments in Delivery of Nucleic Acid-Based Antiviral Agents
Current Pharmaceutical Design Withdrawal Notice: Recent Developments in Anti-Cancer Activity of Compounds Containing the Thioether Group
Anti-Cancer Agents in Medicinal Chemistry Pyrrolo[2,1-c][1,4]benzodiazepine as a Scaffold for the Design and Synthesis of Anti- Tumour Drugs
Anti-Cancer Agents in Medicinal Chemistry Long-circulating Targeted Nanoparticles for Cancer Therapy
Current Nanoscience Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer
Reviews on Recent Clinical Trials Ultrasound Imaging of Cervical Anatomic Variants
Current Medical Imaging Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?
Current Drug Targets Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation
Anti-Cancer Agents in Medicinal Chemistry Targeted Delivery of Short Interfering RNAs - Strategies for In Vivo Delivery
Recent Patents on Anti-Cancer Drug Discovery Urinary Tract Tumors, Biology and Risk for Artificial Sweeteners Use with Particular Emphasis on some South American Countries
Current Nutrition & Food Science Functional Nanoplatforms for Enhancement of Chemotherapeutic Index
Anti-Cancer Agents in Medicinal Chemistry Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy
Current Pharmaceutical Design Molecular Pathology of Sarcomas
Reviews on Recent Clinical Trials Recent Advances in pH-Sensitive Polymeric Nanoparticles for Smart Drug Delivery in Cancer Therapy
Current Drug Targets Cell Cycle Dependent Regulation of Intracellular Calcium Concentration in Vascular Smooth Muscle Cells: A Potential Target for Drug Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Virus-Like Particles as Particulate Vaccines
Current HIV Research