English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/139768
Share/Impact:
Statistics
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
Exportar a otros formatos:

Title

Finding the Right Candidate for the Right Position: A Fast NMR-Assisted Combinatorial Method for Optimizing Nucleic Acids Binders

AuthorsJiménez-Moreno, E.; Montalvillo-Jiménez, L.; Santana, A.G.; Gómez, Ana M. ; Jiménez-Osés, Gonzalo ; Corzana, F.; Bastida, Agatha ; Jiménez-Barbero, Jesús ; Cañada, F. Javier ; Gomez-Pinto, Irene ; González, Carlos ; Asensio, J.L.
Issue Date2016
PublisherAmerican Chemical Society
CitationJournal of the American Chemical Society 138: 6463- 6474 (2016)
AbstractDevelopment of strong and selective binders from promiscuous lead compounds represents one of the most expensive and time-consuming tasks in drug discovery. We herein present a novel fragment-based combinatorial strategy for the optimization of multivalent polyamine scaffolds as DNA/RNA ligands. Our protocol provides a quick access to a large variety of regioisomer libraries that can be tested for selective recognition by combining microdialysis assays with simple isotope labeling and NMR experiments. To illustrate our approach, 20 small libraries comprising 100 novel kanamycin-B derivatives have been prepared and evaluated for selective binding to the ribosomal decoding A-Site sequence. Contrary to the common view of NMR as a low-throughput technique, we demonstrate that our NMR methodology represents a valuable alternative for the detection and quantification of complex mixtures, even integrated by highly similar or structurally related derivatives, a common situation in the context of a lead optimization process. Furthermore, this study provides valuable clues about the structural requirements for selective A-site recognition.
URIhttp://hdl.handle.net/10261/139768
DOI10.1021/jacs.6b00328
Identifiersdoi: 10.1021/jacs.6b00328
issn: 1520-5126
Appears in Collections:(IQFR) Artículos
(IQOG) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


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