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