Methods of screening for compounds that inhibit the...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/54 (2006.01) A61K 31/44 (2006.01) A61K 31/472 (2006.01) A61P 33/06 (2006.01) C07K 14/445 (2006.01) C12N 9/10 (2006.01) C12N 15/12 (2006.01) C12P 21/02 (2006.01) C12Q 1/02 (2006.01) C12Q 1/18 (2006.01) C12Q 1/68 (2006.01) G01N 33/50 (2006.01) G01N 33/569 (2006.01) G01N 33/573 (2006.01)

Patent

CA 2505067

The present inventors succeeded in isolating GWT1 (PfGWT1), which is one of the enzymes involved in GPI biosynthesis in the malaria parasite P. falciparum. In addition, the inventors revealed that degenerate mutant DNAs, with a lower AT content than the DNA encoding the PfGWT1 protein, can complement the phenotype of GWT1-deficient yeast. Based on the findings, the present invention provides the GWT1 protein of malaria parasites and the use of the protein in methods of screening for antimalarial drugs. The present invention also provides degenerate mutant DNAs encoding proteins involved in GPI biosynthesis, and which have a lower AT content than the original DNAs. The present invention also provides methods of screening for antimalarial drugs which use the degenerate mutant DNAs.

Les auteurs de la présente invention ont réussi à isoler la GWT1 (PfGWT1), qui est l'une des enzymes impliquées dans la biosynthèse de GPI chez le parasite de la malaria P. falciparum. En outre, ils ont révélé que des ADN mutants dégénérés, avec une teneur AT inférieure à l'ADN codant pour la protéine PfGWT1, pouvant complémenter le phénotype de levure à déficience de GWT1. Sur la base de ces découvertes, la présente invention a trait à la protéine GWT1 des parasites de la malaria et l'utilisation de la protéine dans des procédés de criblage pour des médicaments antipaludiques. La présente invention a également trait à des ADN mutants dégénérés codant pour les protéines impliquées dans la biosynthèse de GPI, et qui présentent une teneur en AT inférieure à celle des ADN d'origine. Enfin, la présente invention a trait à des procédés de criblage pour des médicaments antipaludiques. mettant en oeuvre les ADN mutants dégénérés.

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