No abstract

UV absorption and fluorescence techniques with a thermal denaturation procedure were used in studies of the anchorage of an oligonucleotide hybridization by a covalently tethered nucleoside analogue of an intercalating imidazophenazine derivative (Pzn). The formation by the (dT)(10)Pzn conjugate of the duplex complex with (dA)(15) and the triplex complex with (dA)(15) or poly(dA).poly(dT) was studied in buffered solutions with 0.11 and/or 1M sodium ions at the oligomer strand concentration of 10 microM. Because of the Pzn emission sensitivity to the interaction with adenine bases, a fluorescence technique was found to be effective in the detection of melting transitions. The attached Pzn substantially enhanced the thermal stability of complexes formed by (dT)(10) because of the intercalation mechanism, which increased the temperature of half-dissociation of the duplex by 10-12 degrees C and of the triplexes by approximately 13 degrees C. With the assumption of a two-state model of transition, the thermodynamic parameters for duplex formations were derived. The investigated variant of conjugation has a certain advantage over the widely used attachment via a flexible linker, consisting of a predetermined location of the Pzn chromophore in target sequences that makes it useful as a fluorescent reporter of the hybridization correctness. Molecular modeling was used to construct the geometries of the intercalation sites that turned out to be in conformity with the behavior of the Pzn fluorescence.

Carboxyalkyl derivative of the intercalating agent imidazo[4,5-b]phenazine was used for the postsynthetic oligonucleotide modification. Model pentadecathymidylate-imidazophenazine conjugate was prepared from 5'-aminoalkyl-modified (dT)(15) by using phosphonium coupling reagent BOP in the presence of 1-hydroxybenzotriazole. Spectral-fluorescent properties of the conjugate were studied. The attachment of the dye was found to increase the thermal stability of (dT)(15) duplex with poly(dA) by more than 4°C, probably by the intercalation mechanism.

Запорізький національний університет Вул. Жуковського, 66, Запоріжжя, 69600, Україна * Інститут біоорганічної хімії та нафтохімії НАН України Вул. Мурманська, 1, Київ, 02094, Україна ефект виявлено у f$-(8метокси-2-метилхінолін-4-ілтіо)-молочної кислоти, яка наближає до норми рівень ферментатив ної активності та білоксинтезувальну функцію печінки. Показано, що досліджені сполуки перспек тивні як потенційні гепатопротектори. На моделі гострого токсичного гепатиту досліджено біологічну дію (8-метокси-2-метилхінолін-4-ілтіо)-карбонових кислот. Найвираженіший мембраностабілізувальний

The preparation of 3'-mono-and 3', 5'-bis-labeled oligonucleotides on a new fluorescein-functionalized polymer support based on Silochrom-2 microspherical silica is described. Oligonucleotide (dT) 15 containing a dye residue at 3'-end was synthesized on this support by solid-phase phosphoramidite method. Post-synthetic 5'-modification of 3'-conjugate allowed obtaining double dye-labeled oligomer.