Noncovalent Interaction of G-Quadruplex DNA with Acridine at Low Concentration Monitored by MALDI-TOF Mass Spectrometry

Abstract

The telomeric G-rich single-stranded DNA d(T₂G₈) can adopt in vitro G-quadruplex structure, even at low DNA concentration. Studies on stability of telomeric structures, has gained importance recently as the molecules, which can stabilize quadruplex structure, can inhibit cancer progression. In this study, G-quadruplex structure is formed by 1.0 mM NH₄(I) ion. Stability of G-quadruplex complex is studied on interaction with acridine using CD and MALDI-TOF mass spectrometry. MALDI-TOF mass spectrometric experiments were carried out mainly to observe the noncovalent drug-DNA interactions at low concentration. From MALDI-TOF spectrum, it is identified that three ammonium ions are required for the formation of G-quadruplex structure and to provide stability to NH₄(I)-G-quadruplex complex. With MALDI-TOF it is evident that two acridine molecules interact with NH₄(I) G-quadruplex complex. CD studies, shows that stability of NH₄(I) G-quadruplex, decreases and conformation change takes place on interaction with acridine. Interaction with drug reduces mostly due to transformation of G-quadruplex complex to single stranded DNA.

Keywords:

• G-quadruplex DNA
• acridine
• noncovalent interactions
• MALDI-TOF
• CD

Acknowledgments

We are thankful to Director, CCMB, Hyderabad for allowing us to use the facilities. We are thankful to Dr. K. Thangaraj for the suggestions and discussions during the preparation of this manuscript. We are thankful to Mrs. Mehar Sultana for providing the oligonucleotides.