J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M400389-JLR200 on January 1, 2005

Papers In Press, published online ahead of print April 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400389-JLR200
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Journal of Lipid Research, Vol. 46, 650-657, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Identification of mosquito sterol carrier protein-2 inhibitors

Min-sik Kim, Vilena Wessely and Que Lan1

Department of Entomology, University of Wisconsin–Madison, Madison, Wisconsin

The online version of this article (available at http://www.jlr.org) contains an additional two figures.

Published, JLR Papers in Press, January 1, 2005. DOI 10.1194/jlr.M400389-JLR200

1 To whom correspondence should be addressed. e-mail: qlan{at}entomology.wisc.edu

A mosquito sterol carrier protein-2, AeSCP-2, has been shown to aid in the uptake of cholesterol in mosquito cells. The discovery of chemical inhibitors of AeSCP-2 is reported here. AeSCP-2 inhibitors (SCPIs) belong to several chemotypes of hydrophobic compounds. Those inhibitors competed with cholesterol for AeSCP-2, binding with relatively high binding affinities. In cultured insect cells, SCPIs reduced cholesterol uptake by as much as 30% at 1–5 µM concentrations. SCPIs were potent larvicides to the yellow fever mosquito, Aedes aegypti, and to the tobacco hornworm, Manduca sexta, with 50% lethal doses (LD50s) of 5–21 µM and 0.013–15 ng/mg diet, respectively.

The results indicate that sterol carrier protein-2 has functional similarity in two different insect species.

Supplementary key words cholesterol • insecticide • high throughput screening

Abbreviations: GST, glutathione S-transferase; HDLp, high density lipophorin; RBA, relative binding affinity; SCP, sterol carrier protein; SCP-2, sterol carrier protein-2; SCP-x, sterol carrier protein-x; SCPI, sterol carrier protein-2 inhibitor


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