In silico design and molecular modeling of peptidic stabilizers of G-quadruplex

Document Type : Research Paper


1 Department of medicinal chemistry, school of pharmacy, hamadan university of medical sciences, hamadan, iran

2 Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

3 Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran


Molecular modeling has a key role in drug discovery and development projects. Virtual screening methods reduce the cost of drug discovery. The role of molecular modeling methods are undeniable in development of anticancer drugs. G-quadruplexes are distinct secondary structures adopted in some guanine-rich DNA sequences. G-quadruplex forms in the promoter of oncogenes and suppresses transcriptional activity. So G-quadruplex stabilizing agents are one of the most potential anticancer agents. In the present contribution, we evaluate the interaction of DSM peptide with G-quadruplex and also design and molecular modeling of new G-quadruplex peptidic stabilizers. According to obtained results, two basic groups are the main parameter in binding to G-quadruplex. In two best designed chains, KGREIGYAK and KGREIGMYAK, lysine and arginine residues place in optimum distance and showed high affinity to G-quadruplex. These basic residues formed ionic bond with phosphate groups of DNA. Tyrosine residue formed π-π interaction with guanine ring of G4.


Main Subjects

Volume 35, Issue 2
June 2022
Pages 316-331
  • Receive Date: 09 July 2019
  • Revise Date: 28 March 2020
  • Accept Date: 28 September 2020
  • First Publish Date: 26 November 2020