The quinoline-based drug, N-{4-[1-hydroxy-2-(dibutylamino)ethyl] quinolin-8-yl}-4-azidosalicylamide, photoaffinity labels the multidrug resistance protein (MRP) at a biologically relevant site

Abstract

MRP is a member of the ABC trafficking proteins thought to mediate the transport of glutathione S-conjugates and amphiphilic natural products. However, unlike P-glycoprotein, the biochemical mechanism by which MRP mediates the resistance to cytotoxic drugs is not clear. In this report, we describe the interactions of a quinoline-based drug, N-{4-[1-hydroxy-2-(dibutylamino)ethyl] quinolin-8-yl}-4-azidosalicylamide (IAAQ), with MRP. Our results demonstrate the ability of IAAQ to photoaffinity label a 190 kDa protein in resistant Small Cell Lung Cancer cells (H69/AR) but not in the parental H69 cells. The photoaffinity labeling of the 190 kDa protein with IAAQ was both saturable and specific. T..