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

Date

2018-12-06

Author

Tutuncu, Serra
Guloglu, Sercan
Kucukakdag, Ayca
Persil Çetinkol, Özgül

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

115
views

0
downloads

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.

Subject Keywords

Benzimidazole, Triplex, Small molecule binding, Drug design, DNA structure

URI

https://hdl.handle.net/11511/37608

Journal

CHEMISTRYSELECT

DOI

https://doi.org/10.1002/slct.201802802

Collections

Department of Chemistry, Article

Suggestions

OpenMETU
Core

Characterisation of immune responses in type I interferon associated diseases Gül, Ersin; Gürsel, Mayda; Department of Biology (2016) Type-I interferonopathies are a heterogeneous group of diseases arising from deregulation in nucleic acid sensing pathways, leading to constitutive type-I interferon release and pathology. DNA damage, if not repaired can also potentially activate such pathways. To test the hypothesis that 2 different DNA damage repair and immune deficiencies, Ataxia telangiectasia (AT) and Artemis deficiency could suffer from clinical manifestations associated with elevated type I IFN response, we compared the immune status...
CpG DNA: recognition by and activation of monocytes. Klinman, DM; Takeshita, F; Gursel, I; Leifer, C; Ishii, KJ; Verthelyi, D; Gürsel, Mayda (2002-07-01) Unmethylated CpG motifs present in bacterial DNA rapidly trigger an innate immune response characterized by the activation of Ig- and cytokine-secreting cells. Synthetic oligonucleotides (ODNs) containing CpG motifs mimic this activity, triggering monocytes to proliferate, secrete and/or differentiate. Analysis of hundreds of novel ODNs led to the identification of two structurally distinct classes of CpG motif that differentially activate human monocytes. ODNs of the "K"-type interact with Toll-like recept...
Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9. Takeshita, F; Gursel, I; Ishii, KJ; Suzuki, K; Gürsel, Mayda; Klinman, DM (2004-02-01) Synthetic oligodeoxynucleotides (ODN) expressing non-methylated "CpG motifs" patterned after those present in bacterial DNA have characteristic immunomodulatory effects. CpG DNA is recognized as a pathogen-associated molecular pattern, and triggers a rapid innate immune response. CpG ODN are being harnessed for a variety of therapeutic uses, including as immune adjuvants, for cancer therapy, as anti-allergens, and as immunoprotective agents. The signal transduction pathway mediated by the engagement of CpG ...
Stepwise Reversal of Immune Dysregulation Due to STAT1 Gain-of-Function Mutation Following Ruxolitinib Bridge Therapy and Transplantation Kayaoğlu, Başak; Yilmaz, Naz Surucu; Charbonnier, Louis Marie; Geckin, Busranur; Akcay, Arzu; Eltan, Sevgi Bilgic; Ozturk, Gulyuz; ÖZEN, AHMET OĞUZHAN; Karakoc-Aydiner, Elif; Chatila, Talal A.; Gürsel, Mayda (2021-01-01) Purpose Patients with heterozygous gain-of-function (GOF) mutations in STAT1 frequently exhibit chronic mucocutaneous candidiasis (CMC), immunodeficiency and autoimmune manifestations. Several treatment options including targeted therapies and hematopoietic stem cell transplantation (HSCT) are available for STAT1 GOF patients but modalities and outcomes are not well established. Herein, we aimed to unravel the effect of ruxolitinib as a bridge therapy in a patient with sporadic STAT1 T385M mutation to manag...
Targeting human telomeric DNA with azacyanines Küçükakdağ Doğu, Ayça; Persil Çetinkol, Özgül; Department of Chemistry (2019) Small molecules targeting telomeric DNA or its interactions with telomerase have been an active area of cancer research. Within this thesis, a series of five new benzimidazole compounds differing from each other in alkyl chain length and branching in the benzimidazole ring (ethyl, propyl, isopropyl, butyl, and isobutyl) were synthesized and characterized using Nuclear Magnetic Resonance (NMR) spectroscopy, High Resolution Mass spectroscopy and C/H/N elemental analysis. Their interactions with human telomeri...

Citation Formats

S. Tutuncu, S. Guloglu, A. Kucukakdag, and Ö. Persil Çetinkol, “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,” CHEMISTRYSELECT, pp. 12878–12887, 2018, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/37608.