Special Issue "G-Quadruplexes & i-Motif DNA"
A special issue of Molecules (ISSN 1420-3049).
Deadline for manuscript submissions: closed (31 August 2013)
Prof. Dr. Edwin A. Lewis
Department of Chemistry, 1115 Hand Lab, Box 9573, Mississippi State, MS 39762, USA
Phone: +1 662 325 3354
Fax: +1 662 325 1618
Interests: structure, stability, and drug binding properties of G-quadruplex and i-Motif DNA's; biological function of G-quadruplex and i-Motif forming sequences located in the regulatory regions of more than 40% of all human genes; drugability of G-quadruplex and i-Motif features found in the promoter regions of many oncogenes, e.g. c-MYC, Bcl-2, and K-ras; the use of thermodynamics for specific DNA-small molecule interactions in rational drug design
Guanine has long been known to self associate by π-π stacking or into G-tetrads stabilized by Hoogsteen H-bonds between N2 and N7, and N1 and O6 on adjacent guanines. Short G-rich DNA (or RNA) sequences can also form intermolecular G-quadruplexes containing from 1 to 4 DNA strands while longer G-rich sequences can fold back onto themselves forming intramolecular G-quadruplexes. It is now known that G-quadruplex forming sequences are found throughout the genome with more than 40% of all human genes having a potential G-quadruplex forming sequence located within 1 kb of the gene start site. Obviously, wherever there is a G-quadruplex forming sequence in one strand the complimentary strand contains a C-rich sequence capable of forming an i-motif. Even though G-quadruplexes have been studied for more than 20 years, the exact nature of their biological significance, other than in the single strand telomere overhang, is not well understood. It is commonly thought that G-quadruplexes and i-motif DNA must be important in gene regulation. For this reason, the G-quadruplex and i-motif structures represent attractive drug targets; small molecules that can stabilize these structures have been investigated as anti-cancer therapeutics. The stabilized higher order structures cannot bind to proteins required to form the transcriptionally active complex thereby down regulating the gene (or oncogene) having G-rich promoter sequences. Several proteins have been found that recognize quadruplex structure including loop bases and sequence. Other than their biological interest, the g-quadruplex and i-motif structures are gaining interest in the materials and nano-materials areas. G-quadruplex structure is known to be sensitive the stabilizing cation (e.g. Na+ vs. K+) while the i-motif structure is known to be sensitive to pH. These properties raise the possibility that sensors or switches could be fabricated using G-quadruplexes or i-motifs. The general focus of this special issue of Molecules will be to look at the structure, stability and ligand binding properties of G-quadruplexes and i-motifs, particularly from the standpoint of their biological activity or their materials properties.
Dr. Edwin A. Lewis
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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 monthly journal published by MDPI.
- intercalative motif
- drug discovery/design
- ligand binding
- hoogsteen hydrogen bonding
- gene regulation
- conformational switches
Article: A Highly Sensitive Telomerase Activity Assay that Eliminates False-Negative Results Caused by PCR Inhibitors
Molecules 2013, 18(10), 11751-11767; doi:10.3390/molecules181011751
Received: 9 August 2013; in revised form: 5 September 2013 / Accepted: 11 September 2013 / Published: 25 September 2013| Download PDF Full-text (981 KB) | Supplementary Files
Article: Macrocyclic Pyridyl Polyoxazoles: Structure-Activity Studies of the Aminoalkyl Side-Chain on G-Quadruplex Stabilization and Cytotoxic Activity
Molecules 2013, 18(10), 11938-11963; doi:10.3390/molecules181011938
Received: 22 August 2013; in revised form: 10 September 2013 / Accepted: 17 September 2013 / Published: 26 September 2013| Download PDF Full-text (357 KB)
Article: Identification of New Natural DNA G-Quadruplex Binders Selected by a Structure-Based Virtual Screening Approach
Molecules 2013, 18(10), 12051-12070; doi:10.3390/molecules181012051
Received: 4 September 2013; in revised form: 18 September 2013 / Accepted: 22 September 2013 / Published: 30 September 2013| Download PDF Full-text (2354 KB) | Supplementary Files
Molecules 2013, 18(10), 12368-12395; doi:10.3390/molecules181012368
Received: 14 August 2013; in revised form: 24 September 2013 / Accepted: 27 September 2013 / Published: 8 October 2013| Download PDF Full-text (1219 KB)
Article: The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH
Molecules 2013, 18(10), 12751-12767; doi:10.3390/molecules181012751
Received: 16 August 2013; in revised form: 26 September 2013 / Accepted: 10 October 2013 / Published: 15 October 2013| Download PDF Full-text (423 KB) | Supplementary Files
Review: Effect of Pressure on Thermal Stability of G-Quadruplex DNA and Double-Stranded DNA Structures
Molecules 2013, 18(11), 13297-13319; doi:10.3390/molecules181113297
Received: 30 August 2013; in revised form: 5 October 2013 / Accepted: 24 October 2013 / Published: 29 October 2013| Download PDF Full-text (1527 KB)
Molecules 2013, 18(11), 13446-13470; doi:10.3390/molecules181113446
Received: 27 September 2013; in revised form: 21 October 2013 / Accepted: 23 October 2013 / Published: 30 October 2013| Download PDF Full-text (798 KB)
Molecules 2013, 18(11), 13588-13607; doi:10.3390/molecules181113588
Received: 30 August 2013; in revised form: 26 October 2013 / Accepted: 29 October 2013 / Published: 4 November 2013| Download PDF Full-text (1736 KB) | Supplementary Files
Article: Targeting C-myc G-Quadruplex: Dual Recognition by Aminosugar-Bisbenzimidazoles with Varying Linker Lengths
Molecules 2013, 18(11), 14228-14240; doi:10.3390/molecules181114228
Received: 7 October 2013; in revised form: 4 November 2013 / Accepted: 8 November 2013 / Published: 18 November 2013| Download PDF Full-text (831 KB) | Supplementary Files
Review: G-Quadruplexes as Sensing Probes
Molecules 2013, 18(12), 14760-14779; doi:10.3390/molecules181214760
Received: 9 September 2013; in revised form: 13 November 2013 / Accepted: 13 November 2013 / Published: 28 November 2013| Download PDF Full-text (684 KB)
Article: Helping Eve Overcome ADAM: G-Quadruplexes in the ADAM-15 Promoter as New Molecular Targets for Breast Cancer Therapeutics
Molecules 2013, 18(12), 15019-15034; doi:10.3390/molecules181215019
Received: 25 September 2013; in revised form: 25 November 2013 / Accepted: 26 November 2013 / Published: 5 December 2013| Download PDF Full-text (742 KB)
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.
Type Paper: Article
Title: DNA G-quadruplex-based Molecular Delivery System of Anticancer Agent in Response to Target mRNA
Authors: Hidenobu Yaku, Takashi Murashima, Daisuke Miyoshi and Naoki Sugimoto
Affiliations: Advanced Technology Research Laboratories, Panasonic Co., Ltd.
Frontier Institute for Biomolecular Engineering Research, Konan University
Faculty of Frontiers of Innovative Research in Science and Technology, Konan University,
Abstract: A G-quadruplex-based nanomachine, which can capture and release of a potent anticancer agent, copper(II) anionic phthalocyanine (CuAPC), in response to a target mRNA, is developed. The carrier G-quadruplex is designed to have a long loop, which is complementary to the target oligonucleotide. Since CuAPC can specifically bind to the G-quadruplex against duplex via π-π stacking interaction, unfolding of the G-quadruplex structure by the hybridization of the target oligonucleotide with its loop region should lead to release of the bound CuAPC. For the proof of the concept, G-quadruplexes with 10-30 mer loop, which can hybridize with a target sequence of the EGFR mRNA, were designed. Structural analysis showed that the designed G-quadruplexes form (3+1) or parallel conformations in the presence of 100 mM KCl and 10 mM MgCl2. By employing UV/vis and fluorescence titration experiments, it was found that the G-quadruplexes bind to CuAPC with Kd values of sub-micromolar or micromolar order, and that the G-quadruplexes bound with target RNAs with Kd values of around 10 nM. Furthermore, it was demonstrated that the target RNA allowed the release of CuAPC from the G-quadruplexes.
Type of Paper: Review
Title: High Pressure Effect on Thermal Stability of G-quadruplex DNA and Double Stranded DNA
Authors: Shuntaro Takahashi and Naoki Sugimoto
Affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), and Faculty of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
Abstract: Pressure is one of the thermodynamic parameters, and can induce structural changes according to the volumetric decrease. Although most proteins can denature triggered by pressure over 100 MPa due to the large cavities inside the molecules, a double stranded (ds) DNA rather is stabilized or destabilized very little depending on the sequence and salt conditions. However, the thermal stability of G-quadruplex DNA, which is one of the important non-canonical structures of nucleic acids for gene expressions in a cell, remarkably decreases with increasing pressure. The volumetric analysis determined that human telomeric DNA showed more than 50 cm3 mol-1 of volumetric change during transition of a coil to a quadruplex form. This value is approximately ten times larger than those of dsDNA in a physiological condition. The volumetric analysis also suggested that G-quadruplex DNA involves large amount of hydration change during the transition of coil to quadruplex. In fact, the presence of cosolute such as poly(ethylene glycol) largely repressed the pressure effect on the stability of G-quadruplex due to the alteration of circumstances of hydrating water. This review will provide the importance of gene expressions triggered by a local perturbation of pressure, and highlight the application of high-pressure chemistry in nucleic acids.
Last update: 10 October 2013