Identification of mosquito sterol carrier protein-2 inhibitors.
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 microM 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 microM and 0.013-15 ng/mg diet, respectively. The results indicate that sterol carrier protein-2 has functional similarity in two different insect species.
Kim
Min-sik
MS
Department of Entomology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Wessely
Vilena
V
Lan
Que
Q
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D009033:Culicidae / Q000187:drug effects / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D019476:Insect Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007814:Larva / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D013261:Sterols / Q000378:metabolism*
D002352:Carrier Proteins; D019476:Insect Proteins; D013261:Sterols; D002784:Cholesterol