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dc.contributor.authorBELL, ANGUS
dc.date.accessioned2008-07-04T13:17:34Z
dc.date.available2008-07-04T13:17:34Z
dc.date.issued2005
dc.date.submitted2005en
dc.identifier.citationMonaghan, P. and Fardis, M. and Revill, W.P. and Bell, A. 'Anti-malarial effects of macrolactones related to FK520 (ascomycin) are independent of the immunosuppressive properties of the compounds' in Journal of Infectious Diseases, 191, (8), 2005, pp.1342 - 1349.en
dc.identifier.issn29182
dc.identifier.otherY
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/18020
dc.descriptionPUBLISHEDen
dc.description.abstractThe polyketide macrolactone FK506 inhibits the growth of Plasmodium falciparum in culture and the enzymatic (peptidyl-prolyl cis-trans isomerase [PPIase]) and chaperone activities of a recently identified P. falciparum FK506-binding protein (PfFKBP35). However, the potent immunosuppressive properties of FK506 exclude it from consideration as an antimalarial drug. We describe the antimalarial actions of the related compound FK520 and a number of its nonimmunosuppressive analogues. All compounds were shown to be strong inhibitors of parasite growth, regardless of their immunosuppressive potency. Although some of the compounds inhibited the PPIase activity of recombinant PfFKBP35, they all inhibited the chaperone activity of this bifunctional protein. These findings suggest that the antimalarial effects of this class of drug may be mediated via inhibition of the chaperone activity rather than via the enzymatic activity of PfFKBP35. Elucidating the precise intracellular functions of PfFKBP35 may facilitate the design of more potent inhibitors that retain their specificity for parasite target protein.en
dc.description.sponsorshipFinancial support: Health Research Board of Ireland (grant 40/99 to A.B.).en
dc.format.extent1342en
dc.format.extent1349en
dc.format.extent234174 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherUniversity of Chicago Pressen
dc.relation.ispartofseries191en
dc.relation.ispartofseries8en
dc.rightsYen
dc.subjectmalariaen
dc.subjectPlasmodium falciparumen
dc.titleAnti-malarial effects of macrolactones related to FK520 (ascomycin) are independent of the immunosuppressive properties of the compoundsen
dc.typeJournal Articleen
dc.contributor.sponsorHealth Research Board
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/abell
dc.identifier.rssinternalid29182
dc.identifier.rssurihttp://www.journals.uchicago.edu/doi/pdf/10.1086/428454


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