Format

Send to

Choose Destination
Exp Parasitol. 2014 Mar;138:55-62. doi: 10.1016/j.exppara.2014.02.001. Epub 2014 Feb 15.

Targeting Plasmodium falciparum protein kinases with adenosine analogue-oligoarginine conjugates.

Author information

1
Institute of Chemistry, University of Tartu, Estonia.
2
Department of Physiology, Institute of Biosciences, University of Sao Paulo, Brazil.
3
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
4
Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes Cité Sorbonne, Paris, France.
5
Department of Physiology, Institute of Biosciences, University of Sao Paulo, Brazil. Electronic address: cgarcia@usp.br.
6
Institute of Chemistry, University of Tartu, Estonia. Electronic address: asko.uri@ut.ee.

Abstract

During the last decade, a vast number of inhibitors, ligands and fluorescent probes have evolved for mammalian protein kinases; however, the suitability of these compounds for studies of evolutionarily divergent eukaryotes has mostly been left beyond the scope of research. Here, we examined whether adenosine analogue-oligoarginine conjugates that had been extensively characterized as efficient inhibitors of the human protein kinases are applicable for targeting Plasmodium protein kinases. We demonstrated that ARCs were not only able to bind to and inhibit a representative member of Plasmodium falciparum kinome (cGMP-dependent protein kinase) in biochemical assay, but also affected the general phosphorylation levels in parasites released from the infected red blood cells upon saponin treatment. These findings urge advantaging of already existing biochemical tools, whose initially generic, but intrinsically "tunable" selectivity profiles could be used for dissection of signaling pathways outside the initially defined group of biological targets.

KEYWORDS:

ARC; Fluorescence anisotropy; Malaria; PfPKG; Protein kinase

PMID:
24534615
DOI:
10.1016/j.exppara.2014.02.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center