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Updated: Jan 30, 2026
08:28
Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
8.6K
From alkylating to shape-shifting G-quadruplex ligands: the RHAU peptide story
Lessandro De Paepe1, Simona Marzano2, Camille Vesschemoet1
1Department of Organic and Macromolecular Chemistry, Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281, Building S4, B-9000 Gent, Belgium.
Nucleic Acids Research
|January 29, 2026
Summary
Researchers developed a peptide-based method for covalent targeting of G-quadruplexes (G4s). Modifications to a RHAU helicase-derived peptide enhanced G4 stabilization and alkylation, offering a new tool for G4 research.
Area of Science:
- Biochemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- G-quadruplexes (G4s) are crucial non-canonical nucleic acid structures involved in telomere maintenance and gene regulation.
- Small molecules and peptide ligands are explored for G4 targeting, with peptides offering high specificity and modularity.
Purpose of the Study:
- To develop a peptide-based methodology for covalent G4 targeting.
- To investigate the G4-stabilizing and alkylation potential of modified peptides derived from the RHAU helicase.
Main Methods:
- Design and synthesis of nine photoactivatable peptides based on the RHAU helicase sequence.
- Evaluation of peptide G4-stabilizing effects and alkylation yields.
- Systematic modification of N-terminal residues to assess individual amino acid contributions to G4 stabilization.
Main Results:
- Moderate to high alkylation yields were achieved for G4 targeting.
- N-terminal modifications significantly enhanced the G4 stabilizing potential of the RHAU18 peptide.
- A comprehensive understanding of modified RHAU peptide binding behavior was established.
Conclusions:
- Peptide-based covalent G4 targeting is feasible and effective.
- N-terminal modifications are key to optimizing G4 stabilization by RHAU-derived peptides.
- This study provides a versatile platform for developing novel G4-targeting agents.
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