Interaction of a Short Peptide with G-Quadruplex-Forming Sequences: An SRCD and CD Study

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• DNA G-quadruplexes (G4) are crucial in regulating genomic processes and are implicated in diseases.
• Controlling G4 structures offers therapeutic potential for modulating cellular events.
• Peptides are promising candidates for targeting G4 structures due to their tunable nature.

Purpose of the Study:

• To investigate the interaction between a RHAU helicase-derived peptide and G-quadruplex forming oligonucleotide sequences.
• To determine the peptide's affinity and specificity for different G4 DNA structures (parallel, antiparallel, hybrid).
• To assess the impact of peptide binding on G4 DNA stability under various conditions.

Main Methods:

• Circular dichroism (CD) and synchrotron radiation circular dichroism (SRCD) spectroscopies were employed.
• Interactions were studied in sodium- and potassium-containing buffers.
• Temperature melting and UV denaturation experiments assessed structural stability.

Main Results:

• The peptide exhibited higher affinity for parallel G4 DNA structures.
• The peptide interacted with antiparallel and hybrid G4 structures, inducing a conversion to the parallel conformation.
• Peptide binding stabilized G4 oligonucleotide structures under stress conditions.

Conclusions:

• The RHAU helicase-derived peptide is a potent binder and stabilizer of DNA G-quadruplexes.
• The peptide's ability to convert and stabilize G4 structures has implications for therapeutic strategies.
• This study highlights the potential of peptide-based G4 targeting agents.