NMR, UV-vis and CD study on the interaction of pradimicin BMY-28864 with divalent cations of alkaline earth metal.
In order to clarify the mechanism of the calcium-activated anti-fungal action of pradimicin derivatives, we investigated the compatibility of four divalent metal cations, Ca2+, Mg2+, Sr2+ and Ba2+, when combined with pradimicin BMY-28864 in an aqueous solution. The 1H NMR studies suggest that all the tested cations can induce a chemical exchange between two types of aggregation of BMY-28864 in an aqueous solution. The exchange rate, however, varies according to the cation species. In descending order they are: Ba2+ > Sr2+ > Ca2+ > Mg2+. The differences in the binding ability of BMY-28864 to the cations and the solubility of the chloride salts are explained by the electronegativity of these cations. The UV-Vis and CD spectra of these solutions show isosbestic points that correspond to an exchange process in the cations' binding to BMY-28864. The results provide experimental support for the hypothesis that there is a common mechanism underlying their cations interactions with the antibiotic. The CD study also provided evidence about the stoichiometric relation of the divalent metal ions to the antibiotic, 1:2, which was obtained by NMR analyses.
Hu
M
M
National Institute of Bioscience and Human-Technology, Tsukuba, Ibaraki, Japan.
Ishizuka
Y
Y
Igarashi
Y
Y
Oki
T
T
Nakanishi
H
H
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D001464:Barium / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002942:Circular Dichroism; D008274:Magnesium / Q000737:chemistry; D008673:Metals, Alkaline Earth / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013056:Spectrophotometry, Ultraviolet; D013324:Strontium / Q000737:chemistry; D017186:Titrimetry
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D008673:Metals, Alkaline Earth; C067714:N,N-dimethylpradimicin FA-2; D001464:Barium; D008274:Magnesium; D002118:Calcium; D013324:Strontium