Selective High Binding Affinity of Azacyanines to polyd(A) center dot polyd(T) center dot polyd(T) Triplex: The Effect of Chain Length and Branching on Stabilization, Selectivity and Affinity

Tutuncu S., Guloglu S., Kucukakdag A., Persil Çetinkol Ö.

CHEMISTRYSELECT, vol.3, no.45, pp.12878-12887, 2018 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 3 Issue: 45
  • Publication Date: 2018
  • Doi Number: 10.1002/slct.201802802
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.12878-12887
  • Keywords: Benzimidazole, DNA structure, Drug design, Small molecule binding, Triplex, DNA-BINDING, ACID, RECOGNITION, LIGANDS, HELICES, DESIGN
  • Middle East Technical University Affiliated: Yes


Triplex nucleic acid structures receive considerable attention due to their possible role in anti-gene therapy, several diseases as Friedreich's ataxia and Deoxyribonucleic acid (DNA) based nano-structures. The modulation of triplex formation and its stabilization using small molecules is one way to enhance their utility in such applications. Here, we synthesized five new Azacyanines (Azaethyl (2 b), Azapropyl (2 c), Azaisopropyl (2 d), Azabutyl (2 e), Azaisobutyl (2 f)) and assessed their affinity and selectivity towards polyd(A), polyd(T), polyd(A) polyd(T) and polyd(A) polyd(T) polyd(T) along with the previously synthesized Azamethyl (2 a). Our UV-Vis, CD and competition dialysis results revealed that Azacyanines were selective towards polyd(A) polyd(T) polyd(T) triplex. They were stabilizing triplex structure to different degrees, the degree of stabilization being dependent on the alkyl chain length and branching on the benzimidazole ring. Thermal denaturation temperature of the triplex in the presence of Azacyanines was increasing in order: Azamethyl (2 a) > Azaethyl (2 b) > Azapropyl (2 c) > Azabutyl (2 e)> Azaisobutyl (2 f) > Azaisopropyl (2 d). Our results also demonstrate that, Azamethyl (2 a) was able to disproportionate polyd(A)polyd(T) into intercalated polyd(A)center dot polyd(T)polyd(T) complex.