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Interaction of a short peptide with G-quadruplex-forming sequences: An SRCD and CD study

DOI: 10.3390/pharmaceutics13081104 DOI Help

Authors: Claudia Honisch (Institute of Biomolecular Chemistry of CNR; University of Padua) , Eugenio Ragazzi (University of Padua) , Rohanah Hussain (Diamond Light Source) , John Brazier (University of Reading) , Giuliano Siligardi (Diamond Light Source) , Paolo Ruzza (Institute of Biomolecular Chemistry of CNR)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Pharmaceutics , VOL 13

State: Published (Approved)
Published: July 2021
Diamond Proposal Number(s): 21245

Open Access Open Access

Abstract: G-quadruplex (G4) forming DNA sequences were recently found to play a crucial role in the regulation of genomic processes such as replication, transcription and translation, also related to serious diseases. Therefore, systems capable of controlling DNA and RNA G-quadruplex structures would be useful for the modulation of various cellular events. In particular, peptides represent good candidates for targeting G-quadruplex structures, since they are easily tailored to enhance their functionality. In this work, we analyzed, by circular dichroism and synchrotron radiation circular dichroism spectroscopies, the interaction of a 25-residue peptide deriving from RHAU helicases (Rhau25) with three G-quadruplex-forming oligonucleotide sequences, in both sodium- and potassium-containing buffers, the most relevant monovalent cations in physiological conditions. The peptide displayed greater affinity for the G4 sequences adopting a parallel structure. However, it showed the ability to also interact with antiparallel or hybrid G-quadruplex structures, inducing a conformation conversion to the parallel structure. The stability of the oligonucleotide structure alone or in presence of the Rhau25 peptide was studied by temperature melting and UV denaturation experiments, and the data showed that the interaction with the peptide stabilized the conformation of oligonucleotide sequences when subjected to stress conditions.

Journal Keywords: G-quadruplex DNA; peptide; photo-stability

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: B23-Circular Dichroism

Added On: 26/07/2021 10:08


Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Discovery Structural biology Chemistry Biochemistry

Technical Tags:

Spectroscopy Circular Dichroism (CD)