PHOTOAFFINITY-LABELING OF CHLOROQUINE-BINDING PROTEINS IN PLASMODIUM-FALCIPARUM
- Author(s)
- Foley, M; Deady, LW; Ng, K; Cowman, AF; Tilley, L;
- Details
- Publication Year 1994-03-04,Volume 269,Issue #9,Page 6955-6961
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- A photoreactive analog of chloroquine, N-(4-(4-diethylamino-1 -methylbutylamino) quinolin-6-yl)-4-azido-2-hydroxybenzamide (referred to as ASA-Q), has been synthesized and shown to mimic the action of chloroquine in possessing substantial antimalarial activity against a chloroquine-sensitive strain of Plasmodium falciparum. As for chloroquine, ASA-Q is less effective at killing drug-resistant strains of malaria, and the resistance can be modulated using the reagent verapamil. ASA-Q has been radiolabeled with (NaI)-I-125 and used as a photoaffinity probe for labeling chloroquine-binding proteins in malaria-infected erythrocytes. Two proteins have been identified with apparent molecular masses of 42 and 33 kDa in both chloroquine-sensitive and chloroquine-resistant strains of malaria. Photoaffinity labeling of the two proteins by iodo-ASA-Q and was competitively inhibited by an excess of unlabeled chloroquine. The structurally related antimalarials amodiaquine and quinine also inhibited labeling of the two proteins, while verapamil and doxycyclin had no effect. We suggest that the two labeled proteins are the macromolecular targets of chloroquine action in malaria parasites.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- MULTIDRUG-RESISTANCE GENE; HUMAN MALARIA PARASITES; ANTIMALARIAL SCHIZONTOCIDES; MECHANISM; PH; IDENTIFICATION; PROTEASE; INVITRO
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- Refer to copyright notice on published article.
Creation Date: 1994-03-04 12:00:00