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

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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Bibliographic Details
Main Authors: Patrick Ball, Robert Hobbs, Simon Anderson, Emma Thompson, Vanessa Gwenin, Christopher Von Ruhland, Christopher Gwenin
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Pharmaceutics
Subjects:
cancer
nitroreductase
prodrug
CB1954
DEPT
Online Access:https://www.mdpi.com/1999-4923/13/4/517
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spelling doaj-24a62a4fe0ae4f908ea6f8377f2c00412021-04-09T23:00:05ZengMDPI AGPharmaceutics1999-49232021-04-011351751710.3390/pharmaceutics13040517The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy ApproachPatrick Ball0Robert Hobbs1Simon Anderson2Emma Thompson3Vanessa Gwenin4Christopher Von Ruhland5Christopher Gwenin6School of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UKSchool of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UKSchool of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UKSchool of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UKSchool of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UKCollege of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XN, UKSchool of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UKThe 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.https://www.mdpi.com/1999-4923/13/4/517cancernitroreductaseprodrugCB1954DEPT
collection DOAJ
language English
format Article
sources DOAJ
author Patrick Ball
Robert Hobbs
Simon Anderson
Emma Thompson
Vanessa Gwenin
Christopher Von Ruhland
Christopher Gwenin
spellingShingle Patrick Ball
Robert Hobbs
Simon Anderson
Emma Thompson
Vanessa Gwenin
Christopher Von Ruhland
Christopher Gwenin
The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach
Pharmaceutics
cancer
nitroreductase
prodrug
CB1954
DEPT
author_facet Patrick Ball
Robert Hobbs
Simon Anderson
Emma Thompson
Vanessa Gwenin
Christopher Von Ruhland
Christopher Gwenin
author_sort Patrick Ball
title 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_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_sort yfko nitroreductase from bacillus licheniformis on gold-coated superparamagnetic nanoparticles: towards a novel directed enzyme prodrug therapy approach
publisher MDPI AG
series Pharmaceutics
issn 1999-4923
publishDate 2021-04-01
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.
topic cancer
nitroreductase
prodrug
CB1954
DEPT
url https://www.mdpi.com/1999-4923/13/4/517
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