Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783683401880961024 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8070144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ballpatrick theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT hobbsrobert theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT andersonsimon theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT thompsonemma theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT gweninvanessa theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT vonruhlandchristopher theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT gweninchristopher theyfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT ballpatrick yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT hobbsrobert yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT andersonsimon yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT thompsonemma yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT gweninvanessa yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT vonruhlandchristopher yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach AT gweninchristopher yfkonitroreductasefrombacilluslicheniformisongoldcoatedsuperparamagneticnanoparticlestowardsanoveldirectedenzymeprodrugtherapyapproach |