Saint Petersburg, St. Petersburg, Russian Federation
The interaction of high molecular DNA with platinum compounds containing the dipeptide D, L-alanyl-L-leucine was studied. The influence of mononuclear and binuclear platinum compounds on DNA conformation in a solution was compared. The mononuclear compound (AL-1) contains a dipeptide in the form of a bidentate ligand attached to the platinum atom in a cis configuration. In the binuclear compound (AL-2), the dipeptide is a common ligand for two platinum atoms. The chlorine atom is in the cis position to this ligand for each platinum atom in AL-2. Compounds are electrolytes and are highly soluble in water. It was shown by the methods of spectrophotometry, circular dichroism, viscometry, and atomic force microscopy, that under the experimental conditions the AL-1 compound does not interact with the DNA molecule, while AL-2 binds to DNA with the coordination of a platinum atom to N7 guanine in the major groove. This is evidenced by an experiment with DNA protonation, that after the formation of DNA complexes with AL-2, the N7 guanine is not available to other agents. Binding appears at both low and high concentrations of supporting electrolyte (NaCl). Thus, not only electrostatic interactions play an important role in the formation of complexes of AL-2 with DNA. The change in the conformational parameters of DNA upon binding (molecular coil volume, bending stiffness or persistent length of DNA) is discussed.
DNA, platinum coordination compounds, solutions
1. Rosenberg B., Vancamp L., Trosko J. E., Mansour V. H. Platinum Compounds: a New Class of Potent Antitumour Agents. Nature, 1969, vol. 222, pp. 385-386.
2. Pinto A.L., Lippard S.J. Binding of the antitumor drug cis- diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim. Biophys. Acta, 1985, vol. 780, pp. 167-180.
3. Zamble D.B., Mu D., Reardon J.T., Sancar A., Lippard S.J. Repair of cisplatin-DNA adducts by the mammalian excision nuclease. Biochemistry, 1996, vol. 35, pp. 10004-10013.
4. Reedijk J., Improved understanding in platinium antitumour chemistry. Chem. Commun., 1996, vol. 7, pp. 801-806.
5. Fichtinger-Schepman A.M., van der Veer J.L., den Hartog J.H., Lohman P.H.M., Reedijk J. Adducts of the antitumor drug cis- diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. Biochemistry, 1985, vol. 24, pp. 707-713.
6. Brabec V., Kleinwächter V., Butour J.L., Johnson N.P. Biophysical studies of the modification of DNA by antitumour platinum coordination complexes. Biophys. Chem., 1990, vol. 35, pp. 129-141.
7. Kas'yanenko N.A., Bogdanov A.A., Defrene S. Vzaimodeystvie molekuly DNK s koordinacionnymi soedineniyami platiny i kobal'ta v rastvore. Biofizika, 2002, t. 47, c. 449-452. @@[Kasyanenko N.A., Bogdanov A.A., De fresne S. Interaction of DNA molecule with coordination compounds of platinum and cobalt in solution. Biofizika, 2002, vol. 47, pp. 449-452. (In Russ.)]
8. Barnham K.J., Bernens-Price S.J., Frenkiel T.A., Frey U., Sadler P.J., Platination Pathways for Reactions of Cisplatin with GG Single-Stranded and Double-Stranded Decanucleotides. Angew. Chem. Int. Ed. Engl., 1995, vol. 34, pp. 1874-1877.
9. Luscombe N.M., Laskowski R.A., Thornton J.M. Amino acid-base interactions: a three-dimensional analysis of protein-DNA interactions at an atomic level. Nucleic Acids Research, 2001, vol. 29, pp. 2860-2874.
10. Chardon E., Dahm G., Guichard G., Bellemin-Laponnaz S. Derivatization of Preformed Platinum N-Heterocyclic Carbene Complexes with Amino Acid and Peptide Ligands and Cytotoxic Activities toward Human Cancer Cells. Organometallics, 2012, vol. 31, pp. 7618-7621.
11. Moradell S., Lorenzo J., Rovira A., van Zutphen S., Avilés F. X., Moreno V., de Llorense R., Martinez M.A., Reedijk J., Llobeta A. Water-soluble platinum(II) complexes of diamine chelating ligands bearing amino-acid type substituents: the effect of the linked amino acid and the diamine chelate ring size on antitumor activity, and interactions with 5′-GMP and DNA. Journal of Inorganic Biochemistry, 2004, vol. 98, pp. 1933-1946.
12. Frisman E.V., Schagina L.V., Vorobiev V.I. A glass rotation viscometer. Biorheology, 1965, vol. 2, pp. 189-194.
13. Kas'ianenko N.A., Valueva S.V., Smorygo N.A., D'iachenko S.A., Frisman E.V. Study of the interaction of a DNA molecule with coordination compounds of divalent platinum I. Effect of cis-diaminodichloroplatinum on molecular parameters of DNA in solution. Mol. Biol. (Mosk.), 1995, vol. 29, pp. 345-353.
14. Kas'ianenko N.A., Karymov M.A., D'iachenko S.A., Smorygo N.A., Frisman E.V. Interaction of DNA molecules with divalent platinum coordination complexes. II. Effect of the nature and location of ligands in the first platinum coordination sphere. Mol. Biol. (Mosk.), 1995, vol. 29, pp. 585-596.
