Role of magnesium ion on the interaction between chromomycin A<sub>3</sub> and deoxyribonucleic acid

Nayak, R.; Sirsi, M

doi:10.1016/0014-5793(73)80641-6

Cited by 32 publications

(28 citation statements)

References 10 publications

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“…The spectral changes are similar to those observed for chromomycin As [9,13], the absorption maximum shifts from 405-440 nm with an isobestic point at 411 nm. Similar spectral changes also occur with DNA-proflavin, DNA-ethidium bromide and DNA-actinomycin D interactions for all of which intercalation is the preferred mode of binding [ 14-161.…”

Section: Resultssupporting

confidence: 76%

“…For this drug to bind to DNA, a divalent cation like Mg2+ is necessary [7], and mithramycin and other structurally related antibiotics like chromomycin A3 and olivomycin are known to be anionic in nature [8]. Nayak et al [9] have shown that the divalent cation is required to counterbalance the electrostatic repulsion between the anionic drug and the negatively charged phosphate groups of DNA. However, it is not clear whether Mg2+ is actually a part of the drug-DNA complex or is independent of it.…”

Section: Introductionmentioning

confidence: 99%

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Nature of interaction of antitumor antibiotic mithramycin with DNA

Prasad

Nayak

1976

FEBS Letters

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Section: Resultssupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Nature of interaction of antitumor antibiotic mithramycin with DNA

Prasad

Nayak

1976

FEBS Letters

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“…However, the interactions of these two drugs with DNA have been the subject of numerous studies. It has been recognized for a long time that such an interaction requires the presence of Mg2+ (Nayak et al, 1973;Van Dyke and Dervan, 1983;Cons and Fox, 1989;Gao and Patel, 1989;Itzhaki et al, 1990;Aich and Dasgupta, 1990;Aich et al, 1992). More recently, it has been proved that Zn2+ can replace and are even more efficient than Mg2+ in promoting the drug/DNA and drug/polynucleotide interactions (Itzhaki et al, 1990 ;Demicheli and Garnier-Suillerot, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies of the interaction of mithramycin with Mg2+ and to a lesser extent with Znz+ have already been made (Nayak et al, 1973;Van Dyke and Dervan, 1983;Cons and Fox, 1989;Gao and Patel, 1989;Itzhaki et al, 1990;Aich and Dasgupta, 1990;Demicheli and Garnier-Suillerot, 1991 ;Aich et al, 1992). However, most of these studies were performed using the calcium complex of mithramycin instead of the free drug as the starting material.…”

Section: Interaction Of Mithramycin With Mg2+ and Zn"mentioning

confidence: 99%

Chirality of the interaction of mithramycin with phospatidylcholine‐bilayer membranes in the presence of Mg²⁺ or Zn²⁺

Demicheli

Garnier‐Suillerot

1994

European Journal of Biochemistry

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Binding of the antitumor compound mithramycin to dipalmitoyl-sn-glycerophosphocholine and dimyristoyl-sn-glycerophosphocholine (Myr,GroPCho) model membrane (small unilamellar vesicles, SUV) bilayers was shown to be dependent on the molecular packing of the lipids and on the presence of Zn2+ or Mg2+. The CD properties of mithramycin have been used to follow its complexation to Zn" and to Mg". In the absence of SUV, Mg2+ and Zn2+ are each able to form with mithramycin two types of complexes of different chirality: at low molar ratios of M2+ to mithramycin, a complex in the left-handed conformation is obtained whereas at high molar ratios the complex formed has the right-handed conformation. In the presence of Znz+ or Mg2+, mithramycin binds to SUV in the gel-phase state as a dimer in the left-handed conformation. No binding is observed when SUV are in liquid-crystal state. Mithramycin (structure shown in Scheme 1) is an antitumor antibiotic produced by Streptomyces tanashiensis. This antibiotic, along with structurally related antibiotics like chromomycin A, and olivomycin, belongs to the aureolic acid group (Remers, 1979). Mithramycin is a DNA-binding antibiotic which binds specifically to G+C rich sequences in the presence of Mg2+, resulting in the selective inhibition of DNA-dependent RNA synthesis (Ward et al., 1965;Kennedy et al., 1968). We have recently shown that, in the presence of Mg" or Zn2+, mithramycin binds to DNA and to the righthanded poly(dG-m'dC) as a dimer in a right-handed conformation (m5dC, 5-methyldeoxycytosine ; Abbreviations. Pam,GroPCho, dipalmitoyl-sn-glycerophosphocholine; Myr,GroPCho, dimyristoyl-sn-glycerophosphocholine; SUV, small unilamellar vesicles ; m5dC, 5-methyldeoxycytosine.pose we have used CD spectroscopy which is in this case a very useful tool because of the large CD signal exhibited by these molecules and its sensitivity to small modifications in the molecular conformation.The interactions of mithramycin and chromomycin A, with DNA or polynucleotides have been greatly investigated. However, to reach the DNA inside the cell the drug molecule has to cross the plasma membrane and, as for other antitumor compounds an action at the membrane level cannot be excluded. The phospholipid polar-head-group conformation is an important component of the structure of the phospholipid bilayers, both in pure lipid systems and in cell membranes. They are the first part of a bilayer with which a molecule must contend in order to cross or to interact with the membrane. In this context we have studied the interaction of mithramycin with dipalmitoyl-sn-glycerophosphocholine (Pam,GroPCho) and dimyristoyl-sn-glycerophosphocholine (Myr,GroPCho) model membranes (small unilamellar vesicles, SUV). In both cases we observed that in the presence of Mg2+ or Zn2+, mithramycin binds to SUV in the gel phase but not in the liquid-crystal state and that the M2+ :mithramycin:SUV entities are in a left-handed conformation. MATERIALS AND METHODS Drugs and chemicalsMithramycin was kindly provided by Pfizer Labo...

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“…Numerous papers focus on the requirement of Mg2+ for the binding of Mit or chromomycin to DNA [12][13][14][15]18,191. We have previously shown that MgZf can be substituted by Zn2+, and that this cation is even more efficient than Mg" for the binding of Mit or chromomycin to DNA [l I].…”

Section: Interaction Of Mit With Mg2mentioning

confidence: 99%

Interaction of mithramycin with DNA

Demicheli

Albertini

Garnier‐Suillerot

1991

European Journal of Biochemistry

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The CD and fluorescence properties of mithramycin have been used to follow its complexation to cations such as Mg2+ and Zn2+ and the binding of these complexes to DNA. At low concentration (< 2 pM) in aqueous solution, mithramycin is always in the dimeric state, the conformation of the dimer being either a right-handed screw when the dimer is neutral, or a left-handed screw when the dimer is negatively charged. In the deprotonated state the dimer can bind one cation forming a complex [M2+(Mit-)*] which has a right-handed screw conformation. The stability constants of the complex at 37°C in 0.1 M KCI are 4 x lo5 and 1 x lo6 for Mg2+ and Zn2+, respectively. The complex in the right-handed screw conformation binds DNA. In this case the stability constants of the complex [M2+(Mit-)2] increase and are 3.6 x lo6 and 1.2 x lo7 for Mg2+ and Zn2+, respectively. We were interested by the recent paper of Itzhaki et al. [I21 reporting analogous data for chromomycin and this prompted us to publish the data of our complete study of the interaction of Mit with DNA in the presence either of Mg2+ or Zn". This was monitored using CD, absorption and fluorescence spectroscopy. We show that, in the presence of Mg2+ or Zn", Mit binds to DNA as a dimer in a right-handed screw conformation. MATERIALS AND METHODSMit was purchased from Pfizer Laboratory and used without further purification. The stock solution was prepared in aqueous 0.1 M KC1 and the concentration determined spectroscopically using an absorption coefficient of 10 000 M -'. cm-' at 400 nm. All experiments were carried out in the presence of 0.1 M KCl. For experiments at pH around 7.2, 0.05 M Hepes buffer was used. All other reagents were of the highest quality available and deionized double-distilled water was used throughout the experiments. DNA preparationHigh-molecular-mass calf thymus DNA was purchased from Sigma Chemical CO. and dissolved in Hepes buffer for 3 h under vigorous stirring. A nucleotide absorption coefficient of 6600 M-' . cm-' was used to calculate DNA concentrations from absorbance measurements at 260 nm.

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Role of magnesium ion on the interaction between chromomycin A₃ and deoxyribonucleic acid

Cited by 32 publications

References 10 publications

Nature of interaction of antitumor antibiotic mithramycin with DNA

Nature of interaction of antitumor antibiotic mithramycin with DNA

Chirality of the interaction of mithramycin with phospatidylcholine‐bilayer membranes in the presence of Mg²⁺ or Zn²⁺

Interaction of mithramycin with DNA

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Role of magnesium ion on the interaction between chromomycin A3 and deoxyribonucleic acid

Cited by 32 publications

References 10 publications

Nature of interaction of antitumor antibiotic mithramycin with DNA

Nature of interaction of antitumor antibiotic mithramycin with DNA

Chirality of the interaction of mithramycin with phospatidylcholine‐bilayer membranes in the presence of Mg2+ or Zn2+

Interaction of mithramycin with DNA

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Role of magnesium ion on the interaction between chromomycin A₃ and deoxyribonucleic acid

Chirality of the interaction of mithramycin with phospatidylcholine‐bilayer membranes in the presence of Mg²⁺ or Zn²⁺