Structural and Thermodynamic Analysis of Daunomycin Binding with Desoxyhexanucleotides with Different Base Sequences by NMR Spectroscopy

摘要: Complexation of the anthracycline antibiotic daunomycin (DAU) with self-complementary desoxyhexanucleotides different base sequences in chain, 5′-d(CGTACG) and 5′-d(CGCGCG), is studied aqueous solution. Homonuclear 2D-1H NMR spectroscopy (TOCSY NOESY) heteronuclear 1H–31P (HMBC) are used for complete assignment nonexchangeable proton resonances phosphorus signals qualitative determination preferable DAU binding sites, respectively. Daunomycin preferably intercalated into first d(CG)-site each hexanucleotide, aminosaccharide ring lies minor groove hexamer duplex, partly overlapping third pair. Quantitative analysis complexation was done by analyzing concentration temperature dependences chemical shifts; equilibrium reaction constants thermodynamic parameters formation 1:1, 1:2, 2:1, 2:2 complexes hexamers, as well limiting values shifts were determined The binds triplet sections nucleotide sequence containing two neighboring CG-pairs nitrogen bases flanked AT-pair compared to triplets consisting a three 5′-d(CGCGCG) hexamer. specific depends on character hydrophobic interactions DNA double helix. Calculations have been carried out determine most probable spatial structures 1:2 DAU–desoxyhexanucleotide complexes; results agree X-ray diffraction data.