The impact of spermine competition on the efficacy of DNA-binding Fe(II), Co(II), and Cu(II) complexes of dimeric chromomycin A3

Lu, Wen-Je; Wang, Hui‐Min David; Yuann, Jeu-Ming P.; Huang, Chun-Yu; Hou, Ming-Hon

doi:10.1016/j.jinorgbio.2009.09.003

Cited by 11 publications

(12 citation statements)

References 48 publications

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“…The anticancer antibiotic chromomycin A 3 (Chro), a DNA minor groove binding drug which interferes with replication and transcription is a member of the aureolic family of drugs isolated from Streptomyces griseus [27–29]. This drug contains di- and trisaccharide moieties connected to a β-ketophenol chromophore via O -glycosidic bonds disposed in a 2, 6 relationship about the anthracene ring, with the disaccharide at the two position and the trisaccharide attached at the 6 position (Figure 1).…”

Section: Conformational Polymorphism Of Dna and Dna-drug Complexesmentioning

confidence: 99%

Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Chang

Chen

Hou

2012

IJMS

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175

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Circular dichroism (CD) spectroscopy is an optical technique that measures the difference in the absorption of left and right circularly polarized light. This technique has been widely employed in the studies of nucleic acids structures and the use of it to monitor conformational polymorphism of DNA has grown tremendously in the past few decades. DNA may undergo conformational changes to B-form, A-form, Z-form, quadruplexes, triplexes and other structures as a result of the binding process to different compounds. Here we review the recent CD spectroscopic studies of the induction of DNA conformational changes by different ligands, which includes metal derivative complex of aureolic family drugs, actinomycin D, neomycin, cisplatin, and polyamine. It is clear that CD spectroscopy is extremely sensitive and relatively inexpensive, as compared with other techniques. These studies show that CD spectroscopy is a powerful technique to monitor DNA conformational changes resulting from drug binding and also shows its potential to be a drug-screening platform in the future.

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Section: Conformational Polymorphism Of Dna and Dna-drug Complexesmentioning

confidence: 99%

Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Chang

Chen

Hou

2012

IJMS

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175

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“…complex as observed by ESI-MS measurements A previous report exploring the effect of spermine on the DNA binding efficacy of different [CHR:metal] complexes has shown that [(CHR) 2 :Cu 2? ] complex binds to DNA with a very low efficacy (Lu et al 2009). However, the studies were performed using biotinylated synthetic hairpin DNA with the following sequence-biotin-d(TTGGCCAATGTTTGGCCAA).…”

Section: Discussionmentioning

confidence: 99%

“…Lu et al has proposed a square planar structure for the [(CHR) 2 :Cu 2? ] complex from MD simulation studies (Lu et al 2009). However, the sugar moieties of the antibiotics were not taken into account for the computation of the structure.…”

Section: Discussionmentioning

confidence: 99%

Association of aureolic acid antibiotic, chromomycin A3 with Cu2+ and its negative effect upon DNA binding property of the antibiotic

et al. 2011

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Here we have examined the association of an aureolic acid antibiotic, chromomycin A3 (CHR), with Cu(2+). CHR forms a high affinity 2:1 (CHR:Cu(2+)) complex with dissociation constant of 0.08 × 10(-10) M(2) at 25°C, pH 8.0. The affinity of CHR for Cu(2+) is higher than those for Mg(2+) and Zn(2+) reported earlier from our laboratory. CHR binds preferentially to Cu(2+) in presence of equimolar amount of Zn(2+). Complex formation between CHR and Cu(2+) is an entropy driven endothermic process. Difference between calorimetric and van't Hoff enthalpies indicate the presence of multiple equilibria, supported from biphasic nature of the kinetics of association. Circular dichroism spectroscopy show that [(CHR)(2):Cu(2+)] complex assumes a structure different from either of the Mg(2+) and Zn(2+) complex reported earlier. Both [(CHR)(2):Mg(2+)] and [(CHR)(2):Zn(2+)] complexes are known to bind DNA. In contrast, [(CHR)(2):Cu(2+)] complex does not interact with double helical DNA, verified by means of Isothermal Titration Calorimetry of its association with calf thymus DNA and the double stranded decamer (5'-CCGGCGCCGG-3'). In order to interact with double helical DNA, the (antibiotic)(2) : metal (Mg(2+) and Zn(2+)) complexes require a isohelical conformation. Nuclear Magnetic Resonance spectroscopy shows that the Cu(2+) complex adopts a distorted octahedral structure, which cannot assume the required conformation to bind to the DNA. This report demonstrates the negative effect of a bivalent metal upon the DNA binding property of CHR, which otherwise binds to DNA in presence of metals like Mg(2+) and Zn(2+). The results also indicate that CHR has a potential for chelation therapy in Cu(2+) accumulation diseases. However cytotoxicity of the antibiotic might restrict the use.

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“…Moreover, MTR has been found to cross the blood-brain barrier and is in its preclinical trials in Huntington's disease (Ferrante et al, 2004). Structural analysis revealed that, MTR binds to minor groove of DNA around GC-rich sequences in the presence of bivalent metal ions such as Mg 2+ , Zn 2+ , Co 2+ , Fe 2+ etc (Aich & Dasgupta, 1995;Devi, Pal, Banerjee, & Dasgupta, 2007;Gochin, 1998;Hou & Wang, 2005;Lu, Wang, Yuann, Huang, & Hou, 2009). Previous studies from our laboratory have shown that MTR binds to different types of bivalent metal ions like Mg 2+ , Zn 2+ , and Cu 2+ , of which Mg 2+ belongs to the main group element, whereas Zn 2+ and Cu 2+ are transition metal ions (Aich & Dasgupta, 1995;Devi et al, 2007;Lahiri et al, 2012).…”

Section: Please Scroll Down For Articlementioning

confidence: 99%

“…We can thus propose that the metal center in [(MTR) 2 Mn 2+ ] has an octahedral coordination. The positive value of the difference in the amplitudes of the observed Cotton effects (A = Δε 1 − Δε 2 ) suggests that this octahedral geometry has a right-handed screw conformation (Demicheli, Albertini, & Garnier-Suillerot, 1991;Lu et al, 2009 ] upon binding to chromatin and chromosomal DNA could be ascribed to perturbation of the π → π * transition by the chromomycinone ring upon interaction with DNA.…”

mentioning

confidence: 99%

Association of antitumor antibiotic Mithramycin with Mn²⁺and the potential cellular targets of Mithramycin after association with Mn²⁺

Dutta

Lahiri

Banerjee

et al. 2014

Journal of Biomolecular Structure and Dynamics

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Mithramycin (MTR), an aureolic acid group of antitumor antibiotic is used for the treatment of several types of tumors. We have reported here the association of MTR with an essential micronutrient, manganese (Mn(2+)). Spectroscopic methods have been used to characterize and understand the kinetics and mechanism of complex formation between them. MTR forms a single type of complex with Mn(2+) in the mole ratio of 2:1 [MTR: Mn(2+)] via a two step kinetic process. Circular dichroism (CD) spectroscopic study indicates that the complex [(MTR)2 Mn(2+)] has a right-handed twist conformation similar in structure with the complexes reported for Mg(2+) and Zn(2+). This conformation allows binding via minor groove of DNA with (G, C) base preference during the interaction with double-stranded B-DNA. Using absorbance, fluorescence, and CD spectroscopy we have shown that [(MTR)2 Mn(2+)] complex binds to double-stranded DNA with an apparent dissociation constant of 32 μM and binding site size of 0.2 (drug/nucleotide). It binds to chicken liver chromatin with apparent dissociation constant value 298 μM. Presence of histone proteins in chromatin inhibits the accessibility of the complex for chromosomal DNA. We have also shown that MTR binds to Mn(2+) containing metalloenzyme manganese superoxide dismutase from Escherichia coli.

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The impact of spermine competition on the efficacy of DNA-binding Fe(II), Co(II), and Cu(II) complexes of dimeric chromomycin A3

Cited by 11 publications

References 48 publications

Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Association of aureolic acid antibiotic, chromomycin A3 with Cu2+ and its negative effect upon DNA binding property of the antibiotic

Association of antitumor antibiotic Mithramycin with Mn²⁺and the potential cellular targets of Mithramycin after association with Mn²⁺

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The impact of spermine competition on the efficacy of DNA-binding Fe(II), Co(II), and Cu(II) complexes of dimeric chromomycin A3

Cited by 11 publications

References 48 publications

Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Association of aureolic acid antibiotic, chromomycin A3 with Cu2+ and its negative effect upon DNA binding property of the antibiotic

Association of antitumor antibiotic Mithramycin with Mn2+and the potential cellular targets of Mithramycin after association with Mn2+

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Product

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Association of antitumor antibiotic Mithramycin with Mn²⁺and the potential cellular targets of Mithramycin after association with Mn²⁺