title: Oligonucleotides covalently linked to intercalating agents. Influence of positively charged substituents on binding to complementary sequences.
abstract: A pentamethylene chain was used to covalently link the 3'-phosphate of oligothymidylates to the 9-amino group of an acridine derivative. Positively charged substituents were further attached to the 3'-phosphate group to form 3'-phosphotriesters. These molecules form specific complexes with poly(rA) which involve the formation of a number of A X T base pairs equal to that of thymines in the oligonucleotide. Absorption changes induced in the acridine absorption bands are similar to those expected upon intercalation of the acridine dye between A X T base pairs. The acridine covalently linked to the 3'-phosphate strongly stabilizes the complexes formed with poly(rA) as compared with the corresponding unsubstituted oligodeoxynucleotide. The presence of a positively charged substituent on the 3'-phosphate together with the acridine dye further enhances the interaction. The effect of salt concentration on complex stability depends on the number of negatively charged phosphate groups of the oligodeoxynucleotide and on the nature of the substituents borne by the 3'-phosphate group. When the oligothymidylate is substituted by an acridine dye, the stability of the poly(rA) complexes increases when salt concentration increases. If an additional positively charged substituent is present on the 3'-phosphate group, stability decreases when salt concentration increases for the shortest oligonucleotide (trimer) and increases with longer oligonucleotides. Thermodynamic parameters have been calculated from the concentration dependence of melting temperatures.
authors.forename: U
authors.initials: U
authors.lastname: Asseline
authors.forename: T T
authors.initials: TT
authors.lastname: Nguyen
authors.forename: C
authors.initials: C
authors.lastname: Hélène
mesh_terms: D001483:Base Sequence; D005092:Exonucleases / Q000494:pharmacology; D007364:Intercalating Agents; D009841:Oligonucleotides; D009994:Osmolar Concentration; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D007364:Intercalating Agents; D009841:Oligonucleotides; D005092:Exonucleases