File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Mapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads

TitleMapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads
Authors
Issue Date2012
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/is/journals/current/mbs/mbspub.htm
Citation
Molecular Biosystems, 2012, v. 8 n. 6, p. 1678-1685 How to Cite?
AbstractThe parasite Plasmodium falciparum is the main agent responsible for malaria. In this study, we exploited a recently published chemical library from GlaxoSmithKline (GSK) that had previously been confirmed to inhibit parasite growth of the wild type (3D7) and the multi-drug resistance (D2d) strains, in order to uncover the weak links in the proteome of the parasite. We predicted 293 proteins of P. falciparum, including the six out of the seven verified targets for P. falciparum malaria treatment, as targets of 4645 GSK active compounds. Furthermore, we prioritized druggable targets, based on a number of factors, such as essentiality for growth, lack of homology with human proteins, and availability of experimental data on ligand activity with a non-human homologue of a parasite protein. We have additionally prioritized predicted ligands based on their polypharmacology profile, with focus on validated essential proteins and the effect of their perturbations on the metabolic network of P. falciparum, as well as indication of drug resistance emergence. Finally, we predict potential off-target effects on the human host with associations to cancer, neurological and dermatological disorders, based on integration of available chemical-protein and protein-protein interaction data. Our work suggests that a large number of the P. falciparum proteome is potentially druggable and could therefore serve as novel drug targets in the fight against malaria. At the same time, prioritized compounds from the GSK library could serve as lead compounds to medicinal chemists for further optimization. © 2012 The Royal Society of Chemistry.
Persistent Identifierhttp://hdl.handle.net/10722/181266
ISSN
2015 Impact Factor: 2.829
2015 SCImago Journal Rankings: 1.238
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJensen, Ken_US
dc.contributor.authorPlichta, Den_US
dc.contributor.authorPanagiotou, Gen_US
dc.contributor.authorKouskoumvekaki, Ien_US
dc.date.accessioned2013-02-21T02:03:37Z-
dc.date.available2013-02-21T02:03:37Z-
dc.date.issued2012en_US
dc.identifier.citationMolecular Biosystems, 2012, v. 8 n. 6, p. 1678-1685en_US
dc.identifier.issn1742-206Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/181266-
dc.description.abstractThe parasite Plasmodium falciparum is the main agent responsible for malaria. In this study, we exploited a recently published chemical library from GlaxoSmithKline (GSK) that had previously been confirmed to inhibit parasite growth of the wild type (3D7) and the multi-drug resistance (D2d) strains, in order to uncover the weak links in the proteome of the parasite. We predicted 293 proteins of P. falciparum, including the six out of the seven verified targets for P. falciparum malaria treatment, as targets of 4645 GSK active compounds. Furthermore, we prioritized druggable targets, based on a number of factors, such as essentiality for growth, lack of homology with human proteins, and availability of experimental data on ligand activity with a non-human homologue of a parasite protein. We have additionally prioritized predicted ligands based on their polypharmacology profile, with focus on validated essential proteins and the effect of their perturbations on the metabolic network of P. falciparum, as well as indication of drug resistance emergence. Finally, we predict potential off-target effects on the human host with associations to cancer, neurological and dermatological disorders, based on integration of available chemical-protein and protein-protein interaction data. Our work suggests that a large number of the P. falciparum proteome is potentially druggable and could therefore serve as novel drug targets in the fight against malaria. At the same time, prioritized compounds from the GSK library could serve as lead compounds to medicinal chemists for further optimization. © 2012 The Royal Society of Chemistry.en_US
dc.languageengen_US
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/is/journals/current/mbs/mbspub.htmen_US
dc.relation.ispartofMolecular BioSystemsen_US
dc.subject.meshAntimalarials - Chemistry - Pharmacologyen_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshCluster Analysisen_US
dc.subject.meshDrug Discovery - Methodsen_US
dc.subject.meshGenome, Protozoanen_US
dc.subject.meshGenomics - Methodsen_US
dc.subject.meshPlasmodium Falciparum - Drug Effects - Geneticsen_US
dc.subject.meshSmall Molecule Libraries - Chemistry - Pharmacologyen_US
dc.titleMapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leadsen_US
dc.typeArticleen_US
dc.identifier.emailPanagiotou, G: gipa@hku.hken_US
dc.identifier.authorityPanagiotou, G=rp01725en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1039/c2mb00008cen_US
dc.identifier.pmid22446744-
dc.identifier.scopuseid_2-s2.0-84861142400en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84861142400&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume8en_US
dc.identifier.issue6en_US
dc.identifier.spage1678en_US
dc.identifier.epage1685en_US
dc.identifier.isiWOS:000303776200008-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridJensen, K=7401675251en_US
dc.identifier.scopusauthoridPlichta, D=55220409000en_US
dc.identifier.scopusauthoridPanagiotou, G=8566179700en_US
dc.identifier.scopusauthoridKouskoumvekaki, I=6602787035en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats