PHOTOAFFINITY-LABELING OF MEFLOQUINE-BINDING PROTEINS IN HUMAN SERUM,UNINFECTED ERYTHROCYTES SIND PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES

A photoreactive quinolinemethanol analog, lamino)ethyl]quinolin-8-yl]- 4-azido-2-salicylamide (ASA-MQ) has been synthesized which closely mim ics the action of mefloquine. ASA-MQ possesses potent antimalarial act ivity against a mefloquine-sensitive strain of Plasmodium falciparum a nd shows decreased activity against a mefloquine-resistant parasite st rain. Radioiodinated ASA-MQ has been used in photoaffinity labeling st udies to identify mefloquine-interacting proteins in serum, uninfected erythrocytes and Plasmodium falciparum-infected erythrocytes. We have shown that mefloquine interacts specifically with ape-Al, the major p rotein of serum high density lipoproteins. In addition, mefloquine was shown to interact specifically with the erythrocyte membrane protein, band 7.2b (stomatin). A further two high affinity mefloquine-binding proteins with apparent molecular masses of 22 and 36 kDa were identifi ed in three different strains of Plasmodium falciparum. We suggest tha t these two mefloquine-binding parasite proteins may be involved in th e uptake of mefloquine or may represent macromolecular targets of mefl oquine action in malaria parasites.