English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/214566
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Benchmarking of laboratory evolved unspecific peroxygenases for the synthesis of human drug metabolites

AuthorsGómez de Santos, Patricia ; Cervantes, Fadia V.; Tieves, Florian; Plou Gasca, Francisco José ; Hollmann, Frank; Alcalde Galeote, Miguel
KeywordsUnspecific peroxygenase
Human drug metabolites
Heme access channel
Issue Date29-Mar-2019
CitationTetrahedron 75: 1827- 1831 (2019)
Abstract[EN] By mimicking the role of human liver P450 monooxygenases, fungal unspecific peroxygenases (UPOs) can perform a range of highly selective oxyfunctionalization reactions on pharmacological compounds, including O-dealkylations and hydroxylations, thereby simulating drug metabolism. Here we have benchmarked human drug metabolite (HDM) synthesis by several evolved UPO mutants, focusing on dextromethorphan, naproxen and tolbutamide. The HDM from dextromethorphan was prepared at the semi-preparative scale as a proof of production. The structural analysis of mutations involved in the synthesis of HDMs highlights the heme access channel as the main feature on which to focus when designing evolved UPOs. These variants are becoming emergent tools for the cost-effective synthesis of HDMs from next-generation drugs.
Publisher version (URL)http://dx.doi.org/10.1016/j.tet.2019.02.013
Identifiersdoi: 10.1016/j.tet.2019.02.013
issn: 1464-5416
e-issn: 0040-4020
Appears in Collections:(ICP) Artículos
Files in This Item:
File Description SizeFormat 
Gomez_Benchmarking_tetrahedron_postprint_2019.pdf1,56 MBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.