Duplex-Guided Refolding into Novel G-Quadruplex (3+1) Hybrid Conformations.

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• DNA G-quadruplexes are four-stranded nucleic acid structures formed in guanine-rich sequences.
• These structures play roles in various biological processes, including telomere maintenance and gene regulation.
• The folding pathways and structural diversity of G-quadruplexes are complex and continue to be investigated.

Purpose of the Study:

• To investigate the folding behavior of a specific DNA oligomer with complementary flanking sequences.
• To characterize the different G-quadruplex structures formed by this oligomer.
• To elucidate the structural features of novel hybrid G-quadruplex topologies.

Main Methods:

• Synthesis of a DNA oligomer with complementary 5' and 3' flanking sequences.
• Spectroscopic analysis (e.g., NMR, UV-Vis) to identify and characterize DNA structures.
• Comparison with G-quadruplexes containing 8-bromoguanosine analogues to confirm structural assignments.

Main Results:

• The DNA oligomer with complementary flanking sequences folded into three distinct G-quadruplex species.
• A single parallel G-quadruplex was observed for an oligomer lacking complementary flanking sequences.
• Two novel (3+1) hybrid G-quadruplex structures with a lateral-propeller-propeller loop architecture were identified, coexisting with the parallel fold.

Conclusions:

• Complementary flanking sequences promote the formation of diverse G-quadruplex structures.
• Novel hybrid G-quadruplex topologies with unique loop architectures can be formed.
• Structural characterization using modified nucleosides aids in the unambiguous identification of complex DNA folds.