Abstract
DNA is the chemotherapeutic target for treating diseases of genetic origin. Besides well-known double-helical structures (A, B, Z, parallel stranded-DNA etc.), DNA is capable of forming several multi-stranded structures (triplex, tetraplex, i-motif etc.) which have unique biological significance. The G-rich 3’-ends of chromosomes, called telomeres, are synthesized by telomerase, a ribonucleoprotein, and over-expression of telomerase is associated with cancer. The activity of telomerase is suppressed if the G-rich region is folded into the four stranded structures, called G-quadruplexes (G4-DNAs) using small synthetic ligands. Thus design and synthesis of new G4- DNA ligands is an attractive strategy to combat cancer. G4-DNA forming sequences are also prevalent in other genomic regions of biological significance including promoter regions of several oncogenes. Effective gene regulation may be achieved by inducing a G4-DNA structure within the G-rich promoter sequences. To date, several G4-DNA stabilizing ligands are known. DNA groove binders interact with the duplex B-DNA through the grooves (major and minor groove) in a sequence-specific manner. Some of the groove binders are known to stabilize the G4-DNA. However, this is a relatively under explored field of research. In this review, we focus on the recent advances in the understanding of the G4-DNA structures, particularly made from the human telomeric DNA stretches. We summarize the results of various investigations of the interaction of various organic ligands with the G4-DNA while highlighting the importance of groove binder-G4-DNA interactions.
Keywords: Telomere, telomerase, G-quadruplex, G-quadruplex ligands, groove binding ligands, i-motif, chromosomes, BMVC, transcriptional regulatory regions, alkylating agents
Current Pharmaceutical Design
Title:Recent Developments in the Chemistry and Biology of G-Quadruplexes with Reference to the DNA Groove Binders
Volume: 18 Issue: 14
Author(s): Akash K. Jain and Santanu Bhattacharya
Affiliation:
Keywords: Telomere, telomerase, G-quadruplex, G-quadruplex ligands, groove binding ligands, i-motif, chromosomes, BMVC, transcriptional regulatory regions, alkylating agents
Abstract: DNA is the chemotherapeutic target for treating diseases of genetic origin. Besides well-known double-helical structures (A, B, Z, parallel stranded-DNA etc.), DNA is capable of forming several multi-stranded structures (triplex, tetraplex, i-motif etc.) which have unique biological significance. The G-rich 3’-ends of chromosomes, called telomeres, are synthesized by telomerase, a ribonucleoprotein, and over-expression of telomerase is associated with cancer. The activity of telomerase is suppressed if the G-rich region is folded into the four stranded structures, called G-quadruplexes (G4-DNAs) using small synthetic ligands. Thus design and synthesis of new G4- DNA ligands is an attractive strategy to combat cancer. G4-DNA forming sequences are also prevalent in other genomic regions of biological significance including promoter regions of several oncogenes. Effective gene regulation may be achieved by inducing a G4-DNA structure within the G-rich promoter sequences. To date, several G4-DNA stabilizing ligands are known. DNA groove binders interact with the duplex B-DNA through the grooves (major and minor groove) in a sequence-specific manner. Some of the groove binders are known to stabilize the G4-DNA. However, this is a relatively under explored field of research. In this review, we focus on the recent advances in the understanding of the G4-DNA structures, particularly made from the human telomeric DNA stretches. We summarize the results of various investigations of the interaction of various organic ligands with the G4-DNA while highlighting the importance of groove binder-G4-DNA interactions.
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Cite this article as:
K. Jain Akash and Bhattacharya Santanu, Recent Developments in the Chemistry and Biology of G-Quadruplexes with Reference to the DNA Groove Binders, Current Pharmaceutical Design 2012; 18 (14) . https://dx.doi.org/10.2174/138161212799958396
DOI https://dx.doi.org/10.2174/138161212799958396 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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