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The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach

The bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are m...

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Autores principales: Ball, Patrick, Hobbs, Robert, Anderson, Simon, Thompson, Emma, Gwenin, Vanessa, Von Ruhland, Christopher, Gwenin, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070144/
https://www.ncbi.nlm.nih.gov/pubmed/33918536
http://dx.doi.org/10.3390/pharmaceutics13040517
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author Ball, Patrick
Hobbs, Robert
Anderson, Simon
Thompson, Emma
Gwenin, Vanessa
Von Ruhland, Christopher
Gwenin, Christopher
author_facet Ball, Patrick
Hobbs, Robert
Anderson, Simon
Thompson, Emma
Gwenin, Vanessa
Von Ruhland, Christopher
Gwenin, Christopher
author_sort Ball, Patrick
collection PubMed
description The bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are major limitations to this research, such as the fact that the lowest reported Km for this enzyme far exceeds the maximum dosage of CB1954. Due to these limitations, new enzymes are now being investigated for their potential use in directed enzyme prodrug therapy. One such enzyme that has proved promising is the YfkO nitroreductase from Bacillus Licheniformis. Upon investigation, the YfkO nitroreductase was shown to have a much lower Km (below the maximum dosage) than that of NfnB as well as the fact that when reacting with the prodrug it produces a much more favourable ratio of enzymatic products than NfnB, forming more of the desired 4-hydroxylamine derivative of CB1954.
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spelling pubmed-80701442021-04-26 The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach Ball, Patrick Hobbs, Robert Anderson, Simon Thompson, Emma Gwenin, Vanessa Von Ruhland, Christopher Gwenin, Christopher Pharmaceutics Article The bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are major limitations to this research, such as the fact that the lowest reported Km for this enzyme far exceeds the maximum dosage of CB1954. Due to these limitations, new enzymes are now being investigated for their potential use in directed enzyme prodrug therapy. One such enzyme that has proved promising is the YfkO nitroreductase from Bacillus Licheniformis. Upon investigation, the YfkO nitroreductase was shown to have a much lower Km (below the maximum dosage) than that of NfnB as well as the fact that when reacting with the prodrug it produces a much more favourable ratio of enzymatic products than NfnB, forming more of the desired 4-hydroxylamine derivative of CB1954. MDPI 2021-04-09 /pmc/articles/PMC8070144/ /pubmed/33918536 http://dx.doi.org/10.3390/pharmaceutics13040517 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ball, Patrick
Hobbs, Robert
Anderson, Simon
Thompson, Emma
Gwenin, Vanessa
Von Ruhland, Christopher
Gwenin, Christopher
The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
title The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
title_full The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
title_fullStr The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
title_full_unstemmed The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
title_short The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
title_sort yfko nitroreductase from bacillus licheniformis on gold-coated superparamagnetic nanoparticles: towards a novel directed enzyme prodrug therapy approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070144/
https://www.ncbi.nlm.nih.gov/pubmed/33918536
http://dx.doi.org/10.3390/pharmaceutics13040517
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