Book of Abstracts: Albany 2003

category image Albany 2003
Conversation 13
Abstract Book
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.

Gabrielian Anna1*
Walter Axel2
Sch├╝tz Holger2
Birch-Hirshfeld Eckhard3

1Institute of Molecular Biology
Armenian Academy of Sciences
Hasratyan Str.7
375014, Yerevan, Armenia
Phone: (3741)566839, 524501
2Institute of Molecular Biology
Friedrich-Schiller University Jena
Winzerlayer Str.10
D-07745, Jena, Germany
3Institute of Virology
Friedrich-Schiller University
Jena, Germany