Stapling a G-quadruplex specific peptide

• Main Authors: Yaneva, Militsa Yavorova, Cheong, Vee Vee, Cheng, Jun Kee, Lim, Kah Wai, Phan, Anh Tuân
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Science::Chemistry; G-quadruplex; G-quadruplex-binding Protein
• Online Access: https://hdl.handle.net/10356/143224
• Institution: Nanyang Technological University

G-quadruplex (G4) is a non-canonical four-stranded nucleic acid structure and the RHAU helicase has been identified to have high specificity for recognition of parallel-stranded G4s. We have designed and synthesized two stapled peptide analogues of the G4-specfic motif of RHAU, which preserve the G4 binding ability. Characterization of these peptides identified the stapled variants to exhibit higher helical formation propensity in aqueous buffer in comparison to the native RHAU sequence. Moreover, the stapled peptides exhibit superior enzymatic stability towards α-chymotrypsin. Our stapled RHAU peptides can serve as a new tool for targeting G4 nucleic acid structures.