Stapling a G-quadruplex specific peptide

Biochem Biophys Res Commun. 2020 Oct 8;531(1):62-66. doi: 10.1016/j.bbrc.2020.02.144. Epub 2020 Mar 25.

Abstract

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.

Keywords: G-quadruplex; G-quadruplex-binding protein; RHAU helicase; Stapled peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • DEAD-box RNA Helicases / chemical synthesis
  • DEAD-box RNA Helicases / chemistry*
  • DEAD-box RNA Helicases / metabolism
  • G-Quadruplexes*
  • Humans
  • Models, Molecular
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / metabolism
  • Protein Binding
  • Protein Conformation, alpha-Helical

Substances

  • Peptides
  • DHX36 protein, human
  • DEAD-box RNA Helicases