Book of Abstracts: Albany 2003
June 17-21 2003
The Minor Groove Binding SN-ligands? Influence On The Oligonucleotide Triplex-Duplex-Coil Transitions
The ?paper-clip? type DNA-triplex formation and stability by means of UV-specrtophotometric melting and titration, as well as CD-spectral methods have been investigated. Oligonucleotides (1) Oli-ATT: (5?-A12-L-T12-L-T12-3?) and (2) Oli-TAT: (5?-T12--L-A12-L-T12-3?) can fold both to duplexes and triplexes through linkers (L≡C4). Triplexes (1) and (2) differ by the third strand direction and the hydrogen bonds? type. Synthetic antitumour bis-quarternary heterocyclic compounds SN are AT-specific nonintercalating minor groove binders with two terminal positive charges. These ligands differ from each other by chemical structure variations. The results serve as basis for mathematical analysis of the binding and self-association processes. The molecular modeling to find the best structural conformity, triplex optimization and the complex energy minimization has been made.
It was shown, that any variation of the ligand molecule structure has a strong effect on binding with triple- and double-helical oligonucleotides. Conformational changes of both interactiing molecules were demonstrated. The contribution of each main factor in the triplex-ligand interaction, including electrostatic and desolvation effects, as well as the size and configuration of oligonucleotide minor groove, has been discussed.
1Institute of Molecular Biology