Investigating the interactions of azacyanines with triplex nucleic acids


Thesis Type: Postgraduate

Institution Of The Thesis: Middle East Technical University, Turkey

Approval Date: 2020

Student: Serra Tütüncü

Supervisor: ÖZGÜL PERSİL ÇETİNKOL

Abstract:

Triple helical nucleic acid structures have gained substantial attention with the emergence of anti-sense and anti-gene strategies. In anti-gene strategies, the idea is to form a triple helical structure in the gene by binding a third nucleic acid sequence into the major groove of that gene. Therefore, the binding of transcription proteins, polymerases, etc. to that gene could be prevented to ultimately result in the inhibition of the transcription. One of the challenges in anti-gene strategies is the fact that the third strand’s binding is weak for most triplex forming sequences and it dissociates from the stable duplex easily. One solution to get over this problem is to increase the stability of triplex structures by using small molecules. The design and synthesis of such triplex stabilizing small molecules have drawn considerable in the last decades due to the use of these molecules as therapeutic agents. Within this context, the importance of alkyl chain length and structure on the benzimidazole derivaties of Azacyanine molecules which tigtly and selectively bind to specific triple helix structures have been revealed by the UV-vis, CD and Fluorescence spectroscopies via the thermal denaturation and titration studies. Furthermore, the effect of pH and salt concentration on polyd(A)·polyd(T)·polyd(T)-Azacyanine interactions have also been studied by CD spectroscopy. With viscosity measurements, the binding mode of the Azacyanines to polyd(A)·polyd(T)·polyd(T)- triplex have been determined.