Cooperative binding of a platinum metallointercalation reagent to poly(A).poly(U)

Biochemistry. 1979 Jun 12;18(12):2661-8. doi: 10.1021/bi00579a036.

Abstract

The cationic complex (2-hydroxyethanethiolato)(2,2',2''-terpyridine)platinum(II), [(terpy)Pt(HET)]+, binds cooperatively to poly(A).poly(U) by intercalation. The melting temperature of poly(A).poly(U) in low-salt buffer is increased by 6 degrees C in the presence of [(terpy)Pt(HET)]+, indicating stabilization of the duplex structure by the bound platinum reagent. Viscosity measurements provide evidence for comparable lengthening of the polynucleotide in the presence of [(terpy)Pt(HET)]+ and the intercalating dye, ethidium bromide. Scatchard plots of the binding of [(terpy)Pt(HET)]+ to poly(A).poly(U) and poly(I).poly(C), determined through ultracentrifugation pelleting methods, show large positive curvature, reflecting the strong cooperativity associated with the platinum complex-RNA interaction. The characteristics of the binding isotherms are interpreted in terms of a model where cooperative pair units of [(terpy)Pt(HET)]+ intercalate into the double-stranded polymer. At saturation, two platinum molecules are bound for every three base pairs. This stoichiometry may be compared with the nearest-neighbor-exclusion binding observed previously in the interaction of [(terpy)Pt(HET)]+ and the ethidium cation with DNA, in which one intercalator occupies every other interbase-pair site at saturation. The striking differences observed in the interaction of [(terpy)Pt(HET)]+ with DNA and RNA suggest that drug recognition is sensitive to the constraints imposed by nucleic acid secondary structure.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Kinetics
  • Mathematics
  • Nucleic Acid Conformation
  • Nucleic Acid Denaturation
  • Organoplatinum Compounds*
  • Poly A-U*
  • Pyridines
  • Viscosity

Substances

  • Organoplatinum Compounds
  • Pyridines
  • Poly A-U