Effect of DNA Local Conformation on the Binding
of bis-Netropsins in the DNA Minor Groove

A. N. Surovaya1, S. L. Grokhovsky2, V. F. Pis’menskii1, G. Burkhardt3,
C. Zimmer3, and G. V. Gursky1

1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 117984 Russia
2 Oslo University, Center of Medical Studies, Oslo, Norway
3 Institute of Molecular Biology, Friedrich Schiller University, Jena, Germany

Received May 27, 1998

Abstract—The interactions of oligonucleotide duplexes with two bis-netropsins (bis-Nt) containing a short linker,
cis-diammineplatinum(II) (frame0Nt-Pt(NH3)2-Ntframe1) or a flexible pentamethylene chain (frame2Nt-(CH2)5-Ntframe3),
were studied using CD, UV, and fluorescent spectroscopy. In both ligands, the netropsin moieties were linked
in the same orientation (tail to tail). It was shown that frame4Nt-Pt(NH3)2-Ntframe5 has the strongest affinity to sequence
5'-TTTTAAAA-3'. If the tetra(A) block is situated at the 5' end, the affinity of frame6Nt-Pt(NH3)2-Nt frame7 to DNA
drops. This effect may be due to the ability of the 5'-TTTTAAAA-3' block to bend toward the major groove
to widen the minor one, which favors the binding of frame8Nt-Pt(NH3)2-Ntframe9. Another bis-netropsin,
frame10Nt-(CH2)5-Ntframe11, having a flexible linker and the same orientation of the netropsin fragments as
frame12 Nt-Pt(NH3)2-Ntframe13, has affinity to DNA regardless of the mutual location of the tetra(T) and tetra(A)
blocks. Differential CD spectra simulated for complexes of frame14Nt-Pt(NH3)2-Ntframe15 with oligonucleotide
duplexes having a widened minor groove acquire a characteristic shape with two long-wavelength maxima.
This indicates binding of frame16Nt-Pt(NH3)2-Ntframe17 in the hairpin conformation, in which the netropsin fragments
form a parallel double-stranded motif. It was shown that specific binding of frame18Nt-Pt(NH3)2-Ntframe19 requires
both a certain nucleotide sequence and a certain local conformation of the DNA minor groove.

Key words: bis-netropsins, platinum, specific recognition in DNA minor groove, CD spectroscopy

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