Metal sensitive and DNA concentration dependent structural rearrangement of short oligonucleotide into large suprastructures

Abstract

Formation of higher order structures, such as G-quadruplexes and G-quadruplex based large suprastructures into long G-wires and liquid crystals is promising elements for use in healthcare for drug delivery as they are mechanically and thermally stable. In this study, we studied the structures of short 11-mer oligonucleotide 5′-G₂AG₅AG₂-3′(11Pu) which is observed in 3′-UTR region of c-jun protooncogene. We used circular dichroism, UV-thermal melting, native gel electrophoresis and atomic force microscopy to determine the structure of 11Pu. CD results showed that 11Pu formed a mixed G-quadruplex in the presence of Na⁺ with and without Mg²⁺, while it formed a parallel G-quadruplex in the presence of 100 mM K⁺ with or without Mg²⁺. Cation selectivity in inducing the formation of large superstructures was observed in the presence of 100 mM K⁺ with 10 mM Mg²⁺. On the contrary, 10 mM Ca²⁺ did not induce the suprastructures. It was further demonstrated that Mg²⁺ at low concentration induced a parallel G-quadruplex of 11Pu, whereas at 10 mM Mg²⁺ induced a large suprastructure. AFM Images showed that 11Pu formed a G-wire, a liquid crystals and a crystalline lattice depending on the concentration of 11Pu and Mg²⁺. These insights may be employed to design G quadruplex-based nanowires for targeted drug delivery as well as interesting candidates for molecular nanowires.

Communicated by Ramaswamy H. Sarma

Keywords:

• G-wire
• G-quadruplex
• UV-thermal denaturation
• native gel electrophoresis
• atomic force microscopy
• DNA nanodevice

Acknowledgement

The timely help from Dr. Anupama Kumari, IGIB, CSIR is greatly acknowledged in AFM measurements.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the research grant of “Department of Science and Technology (DST)”, Govt of India [No. SR/FT/LS-21/2010].