• Home
  • Search Results
  • Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.

Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.

Nature chemical biology (2009-09-08)
Jing Yuan, Ronald L Johnson, Ruili Huang, Jennifer Wichterman, Hongying Jiang, Karen Hayton, David A Fidock, Thomas E Wellems, James Inglese, Christopher P Austin, Xin-zhuan Su
ABSTRACT

Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in inhibiting parasite growth; 607 differential chemical phenotypes, defined as pairwise IC(50) differences of fivefold or more between parasite lines, were cataloged. We mapped major determinants for three differential chemical phenotypes between the parents of a genetic cross, and we identified target genes by fine mapping and testing the responses of parasites in which candidate genes were genetically replaced with mutant alleles. Differential sensitivity to dihydroergotamine methanesulfonate (1), a serotonin receptor antagonist, was mapped to a gene encoding the homolog of human P-glycoprotein (PfPgh-1). This study identifies new leads for antimalarial drugs and demonstrates the utility of a high-throughput chemical genomic strategy for studying malaria traits.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Retinoic acid, ≥98% (HPLC), powder
Sigma-Aldrich
Dopamine hydrochloride
Sigma-Aldrich
Hydroxylamine hydrochloride, ReagentPlus®, 99%
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
2,2′-Bipyridyl, ReagentPlus®, ≥99%
Sigma-Aldrich
L-Tryptophan, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
Resveratrol, ≥99% (HPLC)
Sigma-Aldrich
Rotenone, ≥95%
Sigma-Aldrich
Thapsigargin, ≥98% (HPLC), solid film
Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Sigma-Aldrich
Hydroquinone, ReagentPlus®, ≥99%
Sigma-Aldrich
Calcium Ionophore A23187, ≥98% (TLC), powder
Sigma-Aldrich
Nocodazole, ≥99% (TLC), powder
Sigma-Aldrich
Hydrocortisone solution, 50 μM, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
Colchicine, ≥95% (HPLC), powder
Sigma-Aldrich
Hydroxylamine hydrochloride, ACS reagent, 98.0%
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
1,2-Dihydroxybenzene, ReagentPlus®, ≥99%
Sigma-Aldrich
Progesterone, ≥99%
Sigma-Aldrich
(±)-Verapamil hydrochloride, ≥99% (titration), powder
Sigma-Aldrich
(±)-Propranolol hydrochloride, ≥99% (TLC), powder
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Cyclosporin A, 98.5-101.5% (on dried basis)
Sigma-Aldrich
Trimethoprim, ≥98% (HPLC)
Sigma-Aldrich
Brefeldin A, from Penicillium brefeldianum, ≥99% (HPLC and TLC)
Sigma-Aldrich
Isoprenaline hydrochloride
Sigma-Aldrich
Progesterone, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Suramin sodium salt, ≥98% (TLC)
Sigma-Aldrich
(S)-(+)-Camptothecin, ≥90% (HPLC), powder