A short peptide that preferentially binds c-MYC G-quadruplex DNA

Area of Science:

• Molecular Biology
• Genomics
• Biochemistry

Background:

• G-quadruplexes (G4s) are non-canonical DNA structures with diverse biological roles.
• The human genome contains over 700,000 potential G4 structures.
• Targeting specific G4s requires selective molecular probes.

Purpose of the Study:

• To identify a selective tool for probing the MYC G-quadruplex.
• To understand the binding preferences of novel G4-interacting molecules.

Main Methods:

• Inspiration from crystal structure of bovine DHX36 helicase bound to MYC G4.
• Peptide identification and synthesis.
• Binding affinity assays against various G4 structures.

Main Results:

• A short peptide was identified that preferentially binds the MYC G4.
• The peptide exhibits nanomolar (nM) binding affinity for the MYC G4.
• Selective binding was observed over a panel of parallel and non-parallel G4s.

Conclusions:

• A novel peptide tool for selective MYC G4 targeting has been developed.
• This peptide can aid in elucidating the biological functions of the MYC G4.
• The findings pave the way for developing specific G4-interacting agents.