Strand directionality affects cation binding and movement within tetramolecular G-quadruplexes.

Area of Science:

• Biochemistry
• Structural Biology
• Nucleic Acid Chemistry

Background:

• G-quadruplexes are four-stranded nucleic acid structures with significant biological relevance.
• Understanding G-quadruplex formation and stability is crucial for therapeutic applications.
• Modifications to DNA backbones can alter G-quadruplex topology and cation interactions.

Purpose of the Study:

• To investigate the structural consequences of polarity inversion sites in G-rich DNA sequences.
• To determine the cation-binding preferences and ion dynamics within these modified G-quadruplexes.
• To explore the formation of unusual G-quartet arrangements.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study G-quadruplex structures.
• Synthesis of modified oligonucleotides with 5'-5' or 3'-3' polarity inversion sites.
• Analysis of cation binding stoichiometry and ion exchange kinetics.

Main Results:

• All studied oligonucleotides, including modified analogs, formed tetrameric G-quadruplex structures.
• Modified G-quadruplexes exhibited distinct cation-binding preferences and could bind one or two cations.
• Ion exchange was faster at the 3'-end compared to the 5'-end, influenced by strand directionality and all-syn G-quartet formation.
• A novel tetramolecular parallel G-quadruplex containing an all-syn G-quartet was observed for the unmodified d(TG(3)T).

Conclusions:

• Inversion of polarity sites in G-rich sequences leads to G-quadruplexes with altered cation binding and ion dynamics.
• The formation of an all-syn G-quartet represents a significant structural finding in unmodified G-quadruplexes.
• These findings provide insights into the structural plasticity of G-quadruplexes and their potential for cation recognition.