Special Issue "G-Quadruplex Ligands and Cancer"
Deadline for manuscript submissions: 15 March 2019
Prof. Danzhou Yang
Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, Purdue Center for Cancer Research, 201 S. University St., West Lafayette, IN 47907, USA
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Interests: DNA structures and functions; G-quadruplexes; anticancer drugs; NMR; ligand interactions
G-quadruplexes are four-stranded nucleic acid secondary structures, which form in guanine-rich DNA and RNA sequences. Once a laboratory curiosity, these non-canonical structures are now known to form readily under physiological conditions in regions of biological significance, such as human telomeres, oncogene promoter regions, replication initiation sites, and 5’ and 3’-untranslated (UTR) regions. Many G-quadruplex forming sequences are found to be associated with cancer, thus, these non-canonical nucleic acid structures are considered to be attractive molecular targets for cancer therapeutics with novel mechanisms of action. In recent years, G-quadruplexes have received elevated research interest, and G-quadruplex interactive ligands have been identified to exhibit antiproliferative and chemosensitizing effects against tumor models both in vitro and in vivo. Notably, quarfloxin, a G-quadruplex-interactive fluoroquinoline derivative, reached phase II clinical trials for the treatment of carcinoid/neuroendocrine tumors. While significant advances have been made towards targeting G-quadruplex structures, many questions and challenges on the subject remain to be addressed. This Special Issue aims to provide opportunity to share new findings and recent advances on G-quadruplex targeted small-molecules toward the development of new anticancer drugs.
Prof. Danzhou Yang
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access bimonthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- G-quadruplexes nucleic acid secondary structures
- molecular targets for cancer therapeutics
- G-quadruplex-targeted ligands
- anticancer and chemosensitizing effects
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Design and property of ligand-conjugated guanine tract for recovery of mutated G-quadruplexes
Authors: Naoki Sugimoto and Takahashi Shuntaro; [email protected] (N.S.) [email protected] (T.S.)
Abstract: Because the formation of G4 represses the expression of some cancer-related genes, the mutation in a G4 sequence might affect G4 formation and induce cancer progression. In this study, we will report about the development of an oligonucleotide consisting of a ligand-modified guanine tract that replaces the mutated guanine tract and forms stable intermolecular G4s with the other intact guanine tracts. We will show the effect of ligand molecule and the structure of the modified guanine tract on the recovery of the formation of the mutated G4 derived from the human vascular endothelial growth factor (VEGF).
Title: G-Quadruplex targeting ligands: A hope and a new horizon in Cancer therapeutics
Anthors: Nilanjan Banerjee, Suman Panda and Subhrangsu Chatterjee*
Affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Road, Scheme VIIM, Kankurgachi, Kolkata, Pin-700054, India
Abstract: G-quadruplex, a unique secondary structure in nucleic acids found throughout human genome elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, G-quadruplex structure regulates transcription, translation, splicing, telomere stability etc. Changes in its structure and stability lead to differential expression of oncogenes causing cancer. Thus, targeting quadruplex structures with small molecules/ other biologics has shown elevated research interest. Covering previous reports, in this review we try to enlighten the facts on the structural diversity in G-quadruplex ligands aiming to provide newer insights to design first-in-class drugs for the next generation cancer treatment.
Title: Synthetic ligands targeted to selected G-quadruplex as potential anticancer drugs
Authors: Sefan Asamitsu, Shunsuke Obata, Zutao Yu, Toshikazu Bando and Hiroshi Sugiyama*
Affiliation: Department of Chemistry, Graduate School of Science Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, 606-8502, Japan
Abstract: A G-quadruplex (G4) is a well-known nucleic acid secondary structure adopted by guanine-rich sequences and is deeply relevant to various pharmacological/biological events and cancers. Therefore, G4 ligands have attracted great attention as potential anticancer therapies or in molecular probe applications. To date, a large variety of DNA/RNA G4 ligands has been developed by a number of laboratories. In this review, we would like to address the recent researches on synthetic G4 ligands that allow targeting of selected G4s toward the discovery of highly effective anticancer drugs.
Title: Synthesis of macrocyclic hexaoxoazoles with tri-substituted side chains and their stabilization ability of telomeric G-quadruplex
Authors: Kazuo Nagasawa, Yue Ma and Keisuke Iida
Abstract:G-quadruplexes (G4s), forms in guanine rich regions, have been recognized to involve in variety of significant biological functions, thus selective stabilization agents for specific G-quadruplex are required for regulation of the corresponding functions. In this article, we will describe about our recent efforts for developing new series of macrocyclic hexaoxazole type G4 ligands. These ligands enable us to stabilize telomeric G4 preferentially by introducing groove recognition moiety of side chain in the macrocyclic core structure.
Title: Binding of BRACO19 to human Telomeric G-Quadruplexes Probed by All-Atom Molecular Dynamics Simulations with Explicit Solvent
Authors: Babitha Machireddy, Holli-Joi Sullivan and Chun Wu*
Affiliation: College of Science and Mathematics, Rowan University, Glassboro, NJ, 08028 USA
To whom correspondence should be addressed: [email protected]
Abstract: BRACO19, a potent human telomeric DNA G-quadruplex binder, has shown high efficacy to inhibit various tumor cell growth, however its low (62-fold) preferential binding affinity towards DNA G-quadruplex over DNA duplex limits its clinic applications as a cancer drug. High resolution structures of BRACO19 in complex with neither single-stranded telomeric DNA G-quadruplexes nor B-DNA duplex are available yet. Consequently, the binding nature of BRACO19 to these DNA forms remain elusive. In this study, the binding pathway of BRACO19 is characterized by a total of 26 µs molecular dynamics binding simulations with a free ligand (BRACO19) to a DNA duplex and three different topological folds of the human telomeric DNA G-quadruplex (parallel, antiparallel and hybrid).