INTERACTION OF BIOACTIVE HYDROPHOBIC PEPTIDES WITH THE HUMAN MULTIDRUG TRANSPORTER

In this report we demonstrate that various biologically active hydroph obic peptide derivatives, e.g., proteinase inhibitors, chemoattractant s, ionophores, enkephalins, and immunosuppressants, stimulate a membra ne ATPase activity associated with the human multidrug transporter (MD R1). The stimulation of the MDR1-ATPase by these agents does not corre late with their known biochemical or pharmacological activities but ra ther with their hydrophobicity. The peptides that show high-affinity i nteraction with the MDR1-ATPase also interfere strongly with fluoresce nt dye extrusion catalyzed by the multidrug transporter in intact cell s and some have been shown to reverse drug resistance in cultured cell s. These data suggest that several hydrophobic peptides behave as subs trates of the multidrug transporter and may be used to modulate the ch emotherapy resistance of tumor cells.