A scanning calorimetric study of natural DNA and antitumoral anthracycline antibiotic-DNA complexes.
Thermal denaturation of natural DNA in the absence and presence of antitumor anthracycline antibiotics has been studied by adiabatic differential scanning calorimetry. The helix-coil transition is operationally irreversible as measured by DSC. Both the melting temperature and the overall molar transition enthalpy of the DNA samples was dependent on the percentage of GC base pairs. Calorimetric traces of anthracycline-DNA complexes have qualitatively similar features and the significance of this characteristic is discussed. The unsaturated drug-DNA complex melts through complex thermal transitions with one broad endotherm in the same temperature region as free DNA and the other at a higher temperature which is rf (mol ligand per mol DNA in base pairs) value dependent. Antibiotic binding at concentrations close to saturating conditions (rf = 0.2) reverts the melting range to a value near to its original one and increases the thermal stability of the duplex structure by around 30 degrees C. In addition, the calorimetric enthalpy is increased by between 64% and 150%, depending on which ligand was used.
Barceló
F
F
Department of Biology (School of Sciences), University of the Balearic Islands, Palma de Mallorca, Spain.
Escribá
P V
PV
Miralles
F
F
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics*; D004247:DNA / Q000187:drug effects*; D006358:Hot Temperature; D051379:Mice; D008811:Mice, Inbred DBA; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D051381:Rats; D013816:Thermodynamics
D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D004247:DNA