Cyclization of a G4-specific peptide enhances its stability and G-quadruplex binding affinity

Area of Science:

• Biochemistry
• Molecular Biology
• Chemical Biology

Background:

• G-quadruplexes (G4) are non-canonical nucleic acid structures with significant biological roles.
• The RHAU helicase protein recognizes and interacts with parallel-stranded G-quadruplexes via an alpha-helical fragment.

Purpose of the Study:

• To cyclize an alpha-helical fragment of the RHAU helicase.
• To enhance the stability and G-quadruplex binding affinity of the peptide.
• To develop a novel tool for chemical biology investigations.

Main Methods:

• Utilized a high-efficiency ligase for head-to-tail cyclization of the RHAU helicase fragment.
• Characterized the resulting cyclic peptide's stability and binding properties.
• Assessed its utility as an investigational tool in chemical biology.

Main Results:

• Successfully achieved head-to-tail cyclization of the RHAU helicase-derived peptide.
• The cyclic peptide demonstrated superior stability compared to its linear counterpart.
• Enhanced binding affinity to G-quadruplex structures was observed.

Conclusions:

• Cyclic peptides derived from RHAU helicase fragments offer improved stability and binding.
• These cyclic peptides represent promising tools for studying G-quadruplex structures and functions.
• The findings open new avenues for chemical biology applications targeting G-quadruplexes.