Interaction of bioactive hydrophobic peptides with the human multidrug transporter

B. Sarkadi, M. Müller, L. Homolya, Zsolt Holló, J. Seprődi, Ursula A. Germann, Michael M. Gottesman, Elmer M. Price, R. C. Boucher

Research output: Contribution to journalArticle

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Abstract

In this report we demonstrate that various biologically active hydrophobic peptide derivatives, e.g., proteinase inhibitors, chemoattractants, ionophores, enkephalins, and immunosuppressants, stimulate a membrane ATPase activity associated with the human multidrug transporter (MDR1). The stimulation of the MDR1-ATPase by these agents does not correlate with their known biochemical or pharmacological activities but rather with their hydrophobicity. The peptides that show high-affinity interaction with the MDR1-ATPase also interfere strongly with fluorescent dye extrusion catalyzed by the multidrug transporter in intact cells and some have been shown to reverse drug resistance in cultured cells. These data suggest that several hydrophobic peptides behave as substrates of the multidrug transporter and may be used to modulate the chemotherapy resistance of tumor cells.

Original languageEnglish
Pages (from-to)766-770
Number of pages5
JournalFASEB Journal
Volume8
Issue number10
Publication statusPublished - 1994

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Hydrophobic and Hydrophilic Interactions
adenosinetriphosphatase
Adenosine Triphosphatases
transporters
peptides
Peptides
Cells
immunosuppressive agents
chemoattractants
Chemotherapy
Enkephalins
fluorescent dyes
Chemotactic Factors
Ionophores
ionophores
drug resistance
Immunosuppressive Agents
Hydrophobicity
proteinase inhibitors
hydrophobicity

Keywords

  • ATPase activity
  • fluorescent dye extrusion
  • MDR1
  • multidrug transporter
  • P-glycoprotein
  • peptides

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Interaction of bioactive hydrophobic peptides with the human multidrug transporter. / Sarkadi, B.; Müller, M.; Homolya, L.; Holló, Zsolt; Seprődi, J.; Germann, Ursula A.; Gottesman, Michael M.; Price, Elmer M.; Boucher, R. C.

In: FASEB Journal, Vol. 8, No. 10, 1994, p. 766-770.

Research output: Contribution to journalArticle

Sarkadi, B, Müller, M, Homolya, L, Holló, Z, Seprődi, J, Germann, UA, Gottesman, MM, Price, EM & Boucher, RC 1994, 'Interaction of bioactive hydrophobic peptides with the human multidrug transporter', FASEB Journal, vol. 8, no. 10, pp. 766-770.
Sarkadi, B. ; Müller, M. ; Homolya, L. ; Holló, Zsolt ; Seprődi, J. ; Germann, Ursula A. ; Gottesman, Michael M. ; Price, Elmer M. ; Boucher, R. C. / Interaction of bioactive hydrophobic peptides with the human multidrug transporter. In: FASEB Journal. 1994 ; Vol. 8, No. 10. pp. 766-770.
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AU - Müller, M.

AU - Homolya, L.

AU - Holló, Zsolt

AU - Seprődi, J.

AU - Germann, Ursula A.

AU - Gottesman, Michael M.

AU - Price, Elmer M.

AU - Boucher, R. C.

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