Special Issue "G‐quadruplex Ligands: Recent Advances"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (25 November 2023) | Viewed by 1424

Special Issue Editors

Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, via Elio Chianesi, 53, 00146 Rome, Italy
Interests: cancer; G-quadruplex; aging
Dr. Sara Iachettini
E-Mail Website
Guest Editor
IRCCS - Regina Elena National Cancer Institute, 00144 Rome, Italy
Interests: antitumor activity of G-quadruplex ligands; functions of the shelterin protein TRF2; biochemistry, molecular and cellular biology

Special Issue Information

Dear Colleagues,

G-quadruplexes (G4s) are guanine-rich non-canonical secondary structures of nucleic acids which were discovered in vitro almost a half century ago. From the early 1980s onward, these structures have also been identified in eukaryotic cells, first at the level of telomeres and more recently in regulatory regions of certain genes.

Due their involvement in numerous biological processes and in the pathogenesis of several disease, including cancer, the interest in G4s and their targeting has undergone exponential growth over the last few years. Notably, G4 ligands constitute a large family of heterogeneous molecules which exert their functions through recognition, binding and stabilization of G4 structures. In terms of anti-cancer activity, the efficacy of G4 ligands can be attributed to their capability to inhibit telomerase activity (long-term effects) and induce DNA damage and/or modulation of cancer-related genes (short-term effects). Interestingly, while the knowledge concerning the structural organization of G4s has been extensively characterized, the functions, the potential application of these structures and the development of novel G4s are still active research topics worthy of further investigation.

Dr. Zizza Pasquale
Dr. Sara Iachettini
Guest Editors

Manuscript Submission Information

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Keywords

  • G-quadruplex
  • telomeres
  • aging
  • cancer
  • genomic stability
  • G4-ligands
  • DNA damage

Published Papers (1 paper)

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Research

11 pages, 1794 KiB  
Article
Taq-Polymerase Stop Assay to Determine Target Selectivity of G4 Ligands in Native Promoter Sequences of MYC, TERT, and KIT Oncogenes
Pharmaceuticals 2023, 16(4), 544; https://doi.org/10.3390/ph16040544 - 05 Apr 2023
Viewed by 1151
Abstract
Computational and high-throughput experimental methods predict thousands of potential quadruplex sequences (PQSs) in the human genome. Often these PQSs contain more than four G-runs, which introduce additional uncertainty into the conformational polymorphism of the G4 DNA. G4-specific ligands, which are currently being actively [...] Read more.
Computational and high-throughput experimental methods predict thousands of potential quadruplex sequences (PQSs) in the human genome. Often these PQSs contain more than four G-runs, which introduce additional uncertainty into the conformational polymorphism of the G4 DNA. G4-specific ligands, which are currently being actively developed as potential anticancer agents or tools for studying G4 structures in genomes, may preferentially bind to specific G4 structures over the others that can be potentially formed in the extended G-rich genomic region. We propose a simple technique that identifies the sequences that tend to form G4 in the presence of potassium ions or a specific ligand. Thermostable DNA Taq-polymerase stop assay can detect the preferential position of the G4 –ligand binging within a long PQS-rich genomic DNA fragment. This technique was tested for four G4 binders PDS, PhenDC3, Braco-19, and TMPyP4 at three promoter sequences of MYC, KIT, and TERT that contain several PQSs each. We demonstrate that the intensity of polymerase pausing reveals the preferential binding of a ligand to particular G4 structures within the promoter. However, the strength of the polymerase stop at a specific site does not always correlate with the ligand-induced thermodynamic stabilization of the corresponding G4 structure. Full article
(This article belongs to the Special Issue G‐quadruplex Ligands: Recent Advances)
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