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http://hdl.handle.net/10261/256223
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Serran Aguilera, Lucia | es_ES |
dc.contributor.author | Nuti, Roberto | es_ES |
dc.contributor.author | López-Cara, Luisa C. | es_ES |
dc.contributor.author | Gallo Meza, Miguel Angel | es_ES |
dc.contributor.author | Macchiarulo, Antonio | es_ES |
dc.contributor.author | Entrena, Antonio | es_ES |
dc.contributor.author | Hurtado-Guerrero, Ramón | es_ES |
dc.date.accessioned | 2021-12-16T10:55:33Z | - |
dc.date.available | 2021-12-16T10:55:33Z | - |
dc.date.issued | 2015-06-01 | - |
dc.identifier.citation | Molecular Informatics 34 (6-7): 458-466 (2015) | es_ES |
dc.identifier.issn | 1868-1743 | - |
dc.identifier.uri | http://hdl.handle.net/10261/256223 | - |
dc.description | 10 pags, 5 figs, 1 tab | es_ES |
dc.description.abstract | Choline kinase (CK) catalyses the transfer of the ATP γ-phosphate to choline to generate phosphocholine and ADP in the presence of magnesium leading to the synthesis of phosphatidylcholine. Of the three isoforms of CK described in humans, only the α isoforms (HsCKα) are strongly associated with cancer and have been validated as drug targets to treat this disease. Over the years, a large number of Hemicholinium-3 (HC-3)-based HsCKα biscationic inhibitors have been developed though the relevant common features important for the biological function have not been defined. Here, selecting a large number of previous HC-3-based inhibitors, we discover through computational studies a pharmacophore model formed by five moieties that are included in the 1-benzyl-4-(N-methylaniline)pyridinium fragment. Using a pharmacophore-guided virtual screening, we then identified 6 molecules that showed binding affinities in the low μM range to HsCKα1. Finally, protein crystallization studies suggested that one of these molecules is bound to the choline and ATP-binding sites. In conclusion, we have developed a pharmacophore model that not only allowed us to dissect the structural important features of the previous HC-3 derivatives, but also enabled the identification of novel chemical tools with good ligand efficiencies to investigate the biological functions of HsCKα1. | es_ES |
dc.description.sponsorship | The research leading to these results has received funding from the European Community Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (Grant 724 No 283570). We thank the Ministerio de Ciencia e Innovacion of Spain (SAF2009-11955, BFU2010-19504, AP2009-0555) and the Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo (ARAID, Spain). The Diamond Light Source (DLS) at Oxford, especially beamline I04-1 (experiment MX 8035-11) is gratefully acknowledged. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley-VCH | es_ES |
dc.relation | MICINN/SAF2009-11955 | es_ES |
dc.relation | MICINN/BFU2010-19504 | es_ES |
dc.relation | MICINN/AP2009-0555 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/283570 | es_ES |
dc.rights | openAccess | es_ES |
dc.subject | Binding | es_ES |
dc.subject | Hits | es_ES |
dc.subject | Crystallization | es_ES |
dc.subject | Tryptophan fluorescence | es_ES |
dc.subject | Virtual screening | es_ES |
dc.subject | Choline kinase | es_ES |
dc.subject | Pharmacophore model | es_ES |
dc.title | Pharmacophore-Based Virtual Screening to Discover New Active Compounds for Human Choline Kinase α1 | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1002/minf.201400140 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1002/minf.201400140 | es_ES |
dc.identifier.e-issn | 1868-1751 | - |
dc.contributor.funder | European Commission | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Fundación Agencia Aragonesa para la Investigación y el Desarrollo | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100008767 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004837 | es_ES |
dc.identifier.pmid | 27490389 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.grantfulltext | open | - |
item.fulltext | With Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | artículo | - |
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Choline_kinase.pdf | artículo principal | 1,87 MB | Adobe PDF | Visualizar/Abrir |
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