Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:<sup>31</sup>P NMR chemical shift and relaxation investigation

Wilson, W. David; Jones, Robert L.

doi:10.1093/nar/10.4.1399

Cited by 48 publications

(32 citation statements)

References 26 publications

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“…Purely electrostatic associations between drug and nucleic acid, however, produce only small and generally upfield 31 P chemical shifts. [31,32] Our results on large observed downfield shift of 1.29 and 1.05 ppm in T1pG2 and C5pA6, respectively, are supportive of intercalation of adriamycin chromophore between T1 . .…”

Section: Resultssupporting

confidence: 64%

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Agrawal¹,

Govil²,

Barthwal³

2009

Magnetic Reson in Chemistry

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The complexes of adriamycin-d-(TGATCA)(2) and 4'-epiadriamycin-d-(CGATCG)(2) are studied by one- and two-dimensional (31)P nuclear magnetic resonance spectroscopy (NMR) at 500 MHz in the temperature range 275-328 K and as a function of drug to DNA ratio (0.0-2.0). The binding of drug to DNA is clearly evident in (31)P-(31)P exchange NOESY spectra that shows two sets of resonances in slow chemical exchange. The phosphate resonances at the intercalating steps, T1pG2/C1pG2 and C5pA6/C5pG6, shift downfield up to 1.7 ppm and that at the adjacent step shift downfield up to 0.7 ppm, whereas the central phosphate A3pT4 is relatively unaffected. The variations of chemical shift with drug to DNA ratio and temperature as well as linewidths are different in each of the two complexes. These observations reflect change in population of B(I)/B(II) conformation, stretching of backbone torsional angle zeta, and distortions in O-P-O bond angles that occur on binding of drug to DNA. To the best of our knowledge, there are no solution studies on 4'-epiadriamycin, a better tolerated drug, and binding of daunomycin or its analogue to d-(TGATCA)(2) hexamer sequence. The studies report the use of (31)P NMR as a tool to differentiate various complexes. The specific differences may well be the reasons that are responsible for different antitumor action of these drugs due to different binding ability and distortions in DNA.

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Section: Resultssupporting

confidence: 64%

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Agrawal¹,

Govil²,

Barthwal³

2009

Magnetic Reson in Chemistry

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“…Also, 31 P chemical shift of the DNA phosphate bond is a valuable addition technique for monitoring conformational changes in DNA [31]. The 31 P chemical shift is sensitive to interactions of metal complexes with DNA [32,33]. The two amino acids chosen contain an aromatic and an aliphatic side chain and their comparison was attempted.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and DNA binding properties of oligopyridine-ruthenium(II)-amino acid conjugates

Karidi

Reedijk

Hadjiliadis

et al. 2007

Journal of Inorganic Biochemistry

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“…Intercalators induce a downfield shift of the phosphorous resonances in DNA, which is roughly proportional to the unwinding angle of the bases surrounding the binding site (24). On titration with the monomer, the three 31P signals in d(CpGpCpG) continuously moved downfield by 0.06-0.18 ppm depending on the resonance (not shown).…”

Section: Methodsmentioning

confidence: 97%

Geometry of the antitumor drug ditercalinium bisintercalated into d(CpGpCpG)2 by 1H NMR.

Delbarre¹,

Delepierre²,

Garbay³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Rigid 7H-pyrido[4,3-c]carbazole dimers, such as Ditercalinium, are DNA bisintercalators that display high DNA affinity and strong antitumor properties. This activity appears crucially dependent on the geometry of their complexes with DNA. Therefore, structures of the complexes formed by the self-complementary tetranucleotide d(CpGpCpG) with Ditercalinium and with a related monomer were investigated in 0.1 M [2H]acetate buffer (pH 5.5) by using 400-MHz 1H NMR. In both cases, d(CpGpCpG) retained a right-handed duplex structure as shown by exchangeableproton analysis and intramolecular nuclear Overhauser effect measurements. According to the large upfield shifts measured on the base protons (including the iimino proton) and on the aromatic protons of the pyridocarbazole rings, the monomer appears to monointercalate and the dimer to bisintercalate into the tetranucleotide duplex. Ditercalinium dissociates from its complex about 100-1000 times slower than does the monomer. The negative intermolecular nuclear Overhauser effects observed on protons corresponding to the convex edge of the pyridocarbazole rings when the sugar protons are saturated suggest that both ligands intercalate with their chain oriented to the wide groove side of the helix, a situation mimicking that encountered with repressors. Antitumor activity of 7H-pyridocarbazole derivatives is discussed in terms of geometry of the intercalated complexes., is a potent antitumor 7H-pyridocarbazolium dimer under clinical trials in human cancer chemotherapy (1, 2). As expected for this kind of molecule designed to behave as a small synthetic repressor, Ditercalinium bisintercalates into DNA with a binding affinity greater than 108 M-1 (3). The rigid bipiperidine linker has been selected both to inhibit the intramolecular stacking of the two aromatic rings and to increase the lifetime of the complex by hampering displacement of the ligand along the DNA helix. These factors have been shown to favor the emergence of antitumor properties (4). Despite the presence of a rigid linker, any change in the position of the pyridine nitrogen within the tetracycle as well as replacement of the intercalative 7H-pyridocarbazole moiety by a more elongated ellipticine ring (6H-pyrido [4,3-b] (7), which then was assumed to faithfully mimic DNA. Intercalation of the monomer I and bisintercalation of the dimer H into the tetranucleotide helix was deduced from the large shielding effects undergone by the pyridocarbazole, base, and imino protons in the complexes. Nuclear Overhauser effects (NOE), which can probe short contacts between protons and upfield shifts induced by ring-ring stacking, were used to obtain details on the DNA helix conformation and on the positioning of the intercalated ligands in each complex. At variance with classical intercalating agents or with natural bisintercalative antibiotics, Ditercalinium bisintercalates with its linker protruding into the large groove, a situation which mimics that encountered with repressors. MATERIALS AND METHODSThe deoxyt...

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Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:³¹P NMR chemical shift and relaxation investigation

Cited by 48 publications

References 26 publications

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Synthesis, characterization and DNA binding properties of oligopyridine-ruthenium(II)-amino acid conjugates

Geometry of the antitumor drug ditercalinium bisintercalated into d(CpGpCpG)2 by 1H NMR.

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Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:31P NMR chemical shift and relaxation investigation

Cited by 48 publications

References 26 publications

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)2 and 4′‐epiadriamycin–d‐(CGATCG)2, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)2 and 4′‐epiadriamycin–d‐(CGATCG)2, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Synthesis, characterization and DNA binding properties of oligopyridine-ruthenium(II)-amino acid conjugates

Geometry of the antitumor drug ditercalinium bisintercalated into d(CpGpCpG)2 by 1H NMR.

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Product

Resources

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Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:³¹P NMR chemical shift and relaxation investigation

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂, by phosphorus‐31 nuclear magnetic resonance spectroscopy

Studies on drug–DNA complexes, adriamycin–d‐(TGATCA)₂ and 4′‐epiadriamycin–d‐(CGATCG)₂, by phosphorus‐31 nuclear magnetic resonance spectroscopy