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Association of aureolic acid antibiotic, chromomycin A3 with Cu super(2+) and its negative effect upon DNA binding property of the antibiotic
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Association of aureolic acid antibiotic, chromomycin A3 with Cu super(2+) and its negative effect upon DNA binding property of the antibiotic
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Association of aureolic acid antibiotic, chromomycin A3 with Cu super(2+) and its negative effect upon DNA binding property of the antibiotic
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Journal Article
Association of aureolic acid antibiotic, chromomycin A3 with Cu super(2+) and its negative effect upon DNA binding property of the antibiotic
2012
Overview
Here we have examined the association of an aureolic acid antibiotic, chromomycin A3 (CHR), with Cu super(2+). CHR forms a high affinity 2:1 (CHR:Cu super(2+)) complex with dissociation constant of 0.08 10 super(-10) M super(2) at 25 degree C, pH 8.0. The affinity of CHR for Cu super(2+) is higher than those for Mg super(2+) and Zn super(2+) reported earlier from our laboratory. CHR binds preferentially to Cu super(2+) in presence of equimolar amount of Zn super(2+). Complex formation between CHR and Cu super(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) sub(2):Cu super(2+)] complex assumes a structure different from either of the Mg super(2+) and Zn super(2+) complex reported earlier. Both [(CHR) sub(2):Mg super(2+)] and [(CHR) sub(2):Zn super(2+)] complexes are known to bind DNA. In contrast, [(CHR) sub(2):Cu super(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) sub(2) : metal (Mg super(2+) and Zn super(2+)) complexes require a isohelical conformation. Nuclear Magnetic Resonance spectroscopy shows that the Cu super(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 super(2+)and Zn super(2+). The results also indicate that CHR has a potential for chelation therapy in Cu super(2+) accumulation diseases. However cytotoxicity of the antibiotic might restrict the use.
