Abstract
Flavonoids are well known to inhibit the function of the multi-drug-resistance (mdr) transporter by interacting with their ATP binding domains. The precise orientation of these molecules inside the ATP binding pocket is still unclear. We applied the saturation transfer difference (STD) NMR technique to investigate the binding of the flavonoid luteolin and its 7-O-β-D-glycopyranoside to the recombinant nucleotide binding domain (NBD2) of mouse-mdr. First, this NMR technique confirmed binding of both ligands to NBD2, as was determined from tryptophan fluorescence-quenching experiments. Further, the results suggest binding of both luteolin and its 7-O-β-D-glycopyranoside by their polar groups at positions 4, 5, and 3′ to the protein.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- pgp:
-
p-Glycoprotein
- NBD2:
-
C-Terminal nucleotide binding domain of mouse multi drug resistance protein (mdr)
References
Di Carlo G, Mascolo N, Izzo AA, Capasso F (1999) Life Sci 65:337–353
Depeint F, Gee JM, Williamson G, Johnson IT (2002) Proc Nutr Soc 61:97–103
Rice-Evans CA (1994) Free radical damage and its control. Elsevier, Amsterdam
Guthrie N, Carroll KK (1998) Adv Exp Med Biol 439:227–236
Gebhardt R (2002) Planta Med 68:776–779
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA (2001) Am J Clin Nutr 74:418–425
Jinsart W, Ternai B, Polya GM (1991) Biol Chem Hoppe Seyler 372:819–827
Hagiwara M, Inoue S, Tanaka T, Nunoki K, Ito M, Hidaka H (1988) Biochem Pharmacol 37:2987–2992
Hooijberg JH, Broxterman HJ, Heijn M, Fles DL, Lankelma J, Pinedo HM (1997) FEBS Lett 413:344–348
Maitrejean M, Comte G, Barron D, El Kirat K, Conseil G, Di Pietro A (2000) Bioorg Med Chem Lett 10:157–160
De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH (1996) Proc Natl Acad Sci U S A 93:2735–2740
Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL (2000) Mol Cell 6:909–919
Conseil G, Baubichon-Cortay H, Dayan G, Jault JM, Barron D, Di Pietro A (1998) Proc Natl Acad Sci U S A 95:9831–9836
Ferte J, Kuhnel JM, Chapuis G, Rolland Y, Lewin G, Schwaller MA (1999) J Med Chem 42:478–489
Perez-Victoria JM, Chiquero MJ, Conseil G, Dayan G, Di Pietro A, Barron D, Castanys S, Gamarro F (1999) Biochemistry 38:1736–1743
Tchamo DN, Dijoux-Franca MG, Mariotte AM, Tsamo E, Daskiewicz JB, Bayet C, Barron D, Conseil G, Di Pietro A (2000) Bioorg Med Chem Lett 10:1343–1345
Meyer B, Peters T (2003) Angew Chem Int Ed Engl 42:864–890
Yan J, Kline AD, Mo H, Shapiro MJ, Zartler ER (2003) J Magn Reson 163:270–276
Baubichon-Cortay H, Baggetto LG, Dayan G, Di Pietro A (1994) J Biol Chem 269:22983–22989
Di Pietro A, Conseil G, Perez-Victoria JM, Dayan G, Baubichon-Cortay H, Trompier D, Steinfels E, Jault JM, de Wet H, Maitrejean M, Comte G, Boumendjel A, Mariotte AM, Dumontet C, McIntosh DB, Goffeau A, Castanys S, Gamarro F, Barron D (2002) Cell Mol Life Sci 59:307–322
Scambia G, Ranelletti FO, Panici PB, De Vincenzo R, Bonanno G, Ferrandina G, Piantelli M, Bussa S, Rumi C, Cianfriglia M (1994) Cancer Chemother Pharmacol 34:459–464
Shapiro AB, Ling V (1997) Eur J Biochem 250:130–137
Agraval PK (1989) Carbon-C13 NMR of flavonoids. Elsevier, Amsterdam
Exarchou V, Nenadis N, Tsimidou M, Gerothanassis IP, Troganis A, Boskou D (2002) J Agric Food Chem 50:5294–5299
Markham KR, Ternai B, Stanly R, Geiger H, Mabry TJ (1978) Tetrahedron 34:1389–1394
Acknowledgements
This work was supported by grants (SFB 610 and Ge 465/7-1) from the Deutsche Forschungsgemeinschaft.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nissler, L., Gebhardt, R. & Berger, S. Flavonoid binding to a multi-drug-resistance transporter protein: an STD-NMR study. Anal Bioanal Chem 379, 1045–1049 (2004). https://doi.org/10.1007/s00216-004-2701-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-004-2701-3