Nucleic acid-binding molecules with high affinity and base sequence specificity: intercalating agents covalently linked to oligodeoxynucleotides.

摘要: Abstract Oligodeoxyribonucleotides covalently linked to an intercalating agent via a polymethylene linker were synthesized. Oligothymidylates attached acridine dye (Acr) through the 3'-phosphate group [(Tp)n(CH2) mAcr ] specifically interact with complementary sequence. The interaction is strongly stabilized by agent. By using absorption and fluorescence spectroscopies, it shown that complex formation between (Tp)n(CH2) poly(rA) involves of n A X T base pairs, where number thymines in oligonucleotide. ring intercalates pairs. Fluorescence excitation spectra reveal existence two environments for ring, whose relative contributions depend on length (m). binding (Tp)4(CH2) analyzed terms site cooperative interactions oligonucleotides along polynucleotide lattice. Thermodynamic parameters show covalent attachment stabilizes oligonucleotide its stabilization depends length; compound m = 5 gives more stable than 3. These results open way synthesis family molecules exhibiting both high-affinity high-specificity nucleic acid