Mass spectrometric investigation of the DNA-binding properties of an anthracycline with two trisaccharide chains

Kelso, Celine, Tillott, Vanessa, Rojas, Juan Diego, Furlan, Renata L.A., Padilla, Gabriel, and Beck, Jennifer L. (2008) Mass spectrometric investigation of the DNA-binding properties of an anthracycline with two trisaccharide chains. Archives of Biochemistry and Biophysics, 477 (2). pp. 348-355.

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Abstract

Cosmomycin D (CosD) is an anthracycline that has two trisaccharide chains linked to its ring system. Gel electrophoresis showed that CosD formed stable complexes with plasmid DNA under conditions where daunorubicin (Dn) and doxorubicin (Dx) dissociated to some extent during the experiments. The footprint and stability of CosD complexed with 10- and 16 mer DNA was investigated using several applications of electrospray ionisation mass spectrometry (ESI-MS). ESI-MS binding profiles showed that fewer CosD molecules bound to the sequences than Dn or Dx. In agreement with this, ESI-MS analysis of nuclease digestion products of the complexes showed that CosD protected the DNA to a greater extent than Dn or Dx. In tandem MS experiments, all CosD–DNA complexes were more stable than Dn- and Dx-DNA complexes. These results support that CosD binds more tightly to DNA and exerts a larger footprint than Dn or Dx. ESI-MS investigations of the binding properties of CosD could be carried out rapidly and using only small amounts of sample.

Item ID: 19407
Item Type: Article (Refereed Research - C1)
Keywords: anthracyclines; non-covalent complex; electrospray ionisation mass spectrometry; trisaccharide chains; gel mobility shift assay
ISSN: 1096-0384
Date Deposited: 20 Jan 2012 05:11
FoR Codes: 03 CHEMICAL SCIENCES > 0303 Macromolecular and Materials Chemistry > 030301 Chemical Characterisation of Materials @ 50%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060501 Bacteriology @ 50%
SEO Codes: 86 MANUFACTURING > 8608 Human Pharmaceutical Products > 860803 Human Pharmaceutical Treatments (e.g. Antibiotics) @ 100%
Citation Count from Web of Science Web of Science 2
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