Elsamicin A binding to DNA. A comparative thermodynamic characterization.
The antitumor drug elsamicin A contains a coumarin-related chartarin chromophore that intercalates into DNA. It differs from other related molecules in its disaccharide moiety, which bears an amino sugar. Its binding to DNA was analyzed using isothermal titration calorimetry and UV thermal denaturation, and characterized thermodynamically. For the association of elsamicin A with DNA we found DeltaG degrees = -8.6 kcal mol(-1), DeltaH = -10.4 kcal mol(-1), DeltaS = -6.1 cal mol(-1) K(-1), and Kobs = 2.8(+/- 0.2) x 10(6) M(-1) at 20 degrees C in 18 mM Na+. The contributions to the free energy of binding that lead to the DNA-elsamicin complex are compared with the binding to DNA of chartreusin, another chartarin-containing drug. The results are discussed in terms of the contributions of the disaccharide moieties into the strength of binding.
Departament de Biologia Fundamental, i Ciencies de la Salut, Universitat de les Illes Balears, E-07122 Palma de Mallorca, Spain.
Francisca
F
Barceló
José
J
Portugal
D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism*; D001578:Benzopyrans / Q000737:chemistry / Q000378:metabolism; D002151:Calorimetry; D004247:DNA / Q000378:metabolism*; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D013696:Temperature; D013816:Thermodynamics
D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D001578:Benzopyrans; D004187:Disaccharides; D006027:Glycosides; D004247:DNA; C002185:chartreusin; C049904:elsamicin A