G-quadruplexes (G4s) are nucleic acids secondary structures that form in DNA or RNA guanine (G)-rich strands. In recent years, the presence of G4s in microorganisms has attracted increasing interest. ...In prokaryotes, G4 sequences have been reported in several human pathogens. Bacterial enzymes able to process G4s have been identified. In viruses, G4s have been suggested to be involved in key steps of the viral life cycle: They have been associated with the human immunodeficiency virus (HIV), herpes simplex virus 1 (HSV-1), human papilloma virus, swine pseudorabies virus, and other viruses’ genomes. New evidence shows the presence of G4s in parasitic protozoa, such as the causative agent of malaria. G4 binding proteins and mRNA G4s have been implicated in the regulation of microorganisms’ genome replication and translation. G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle and as therapeutic agents. Moreover, new techniques to study G4 folding and their interactions with proteins have been developed. This Special Issue will focus on G4s present in microorganisms, addressing all the above aspects.
Guanine-rich DNA sequences can fold into four-stranded noncanonical secondary structures called G-quadruplexes (G4s) which are widely distributed in functional regions of the human genome, such as ...telomeres and gene promoter regions. Compelling evidence suggests their involvement in key genome functions such as gene expression and genome stability. Notably, the abundance of G4-forming sequences near transcription start sites suggests their potential involvement in regulating oncogenes.
This review provides an overview of current knowledge on G4s in human oncogene promoters. The most representative G4-binding ligands have also been documented. The objective of this work is to present a comprehensive overview of the most promising targets for the development of novel and highly specific anticancer drugs capable of selectively impacting the expression of individual or a limited number of genes.
Modulation of G4 formation by specific ligands has been proposed as a powerful new tool to treat cancer through the control of oncogene expression. Actually, most of G4-binding small molecules seem to simultaneously target a range of gene promoter G4s, potentially influencing several critical driver genes in cancer, thus producing significant therapeutic benefits.
G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, ...and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.
G-quadruplex is a high-level structure composed of folded DNA or RNA rich in tandem repeats of guanine (G). In recent years, G-quadruplex is widely used in various fields due to its unique structural ...properties. This article briefly introduces the structural properties of G-quadruplex, and provides a brief introduction to the research on DNA and RNA G-quadruplex in various detection and medical fields. It is hoped that this can provide some help to readers who want to understand G-quadruplex.
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•The development and spread of G-quadruplex are inextricably linked to the microenvironment in biosystem.•Two or more tetramers form a quadruplex by π-π superposition.•This paper reviews the research advances in G-quadruplex DNA, G-quadruplex aptamer and G-quadruplex DNAzyme.
G-quadruplexes (G4s) are extremely stable DNA or RNA secondary structures formed by sequences rich in guanine. These structures are implicated in many essential cellular processes, and the number of ...biological functions attributed to them continues to grow. While DNA G4s are well understood on structural and, to some extent, functional levels, RNA G4s and their functions have received less attention. The presence of bona fide RNA G4s in cells has long been a matter of debate. The development of G4-specific antibodies and ligands hinted on their presence in vivo, but recent advances in RNA sequencing coupled with chemical footprinting suggested the opposite. In this review, we will critically discuss the biology of RNA G4s focusing on the molecular mechanisms underlying their proposed functions.
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•RNA G-quadruplexes exhibit key differences from DNA G-quadruplexes.•RNA G-quadruplexes exist in vitro but unfolded in vivo.•Specific protein factors recognize and bind RNA G-quadruplexes.•RNA G-quadruplexes regulate multiple aspects of RNA metabolism.•Emerging roles of RNA G-quadruplexes in non-coding transcriptome•Combinations of structural, biophysical, chemical, computational and molecular biology tools can be used to understand the mechanisms that underlie RNA G-quadruplex functions.
G-quadruplexes constitute an important type of nucleic acid structure, which can be found in living cells and applied by cell machinery as pivotal regulatory elements. Importantly, robust development ...of SELEX technology and modern, nucleic acid-based therapeutic strategies targeted towards various molecules have also revealed a large group of potent aptamers whose structures are grounded in G-quadruplexes. In this review, we analyze further extension of tetraplexes by additional structural elements and investigate whether G-quadruplex junctions with duplex, hairpin, triplex, or second G-quadruplex motifs are favorable for aptamers stability and biological activity. Furthermore, we indicate the specific and pivotal role of the G-quadruplex domain and the additional structural elements in interactions with target molecules. Finally, we consider the potency of G-quadruplex junctions in future applications and indicate the emerging research area that is still waiting for development to obtain highly specific and effective nucleic acid-based molecular tools.
G-quadruplex, a structurally unique structure in nucleic acids present all throughout the human genome, has sparked great attention in therapeutic investigations. Targeting G-quadruplex structure is ...a new strategy for the drug development. Flavonoids are found in almost all dietary plant-based beverages and food products; therefore, they are ingested in significant proportions through the human diet. Although synthetically developed drug molecules are used vigorously but they have various adverse effects. While on the other hand, nature supplies chemically unique scaffolds in the form of distinct dietary flavonoids that are easily accessible, less poisonous, and have higher bioavailability. Because of their great pharmacological effectiveness and minimal cytotoxicity, such low molecular weight compounds are feasible alternatives to synthetic therapeutic medicines. Therefore, from a drug-development point of view, investigation on screening the binding capabilities of quadruplex-interactive small natural compounds like dietary flavonoids are expected to be highly effective, with a particular emphasis on the selectivity towards polymorphic G-quadruplex structures. In this respect, quadruplexes have scintillated research into their potential interaction with these dietary flavonoids. The purpose of this review is to offer an up-to-date close-up look at the research on their interaction with structurally varied dietary flavonoids with the goal of providing newer perspectives to construct novel therapeutic agents for next-generation disease managements.
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•Humans consume considerable amounts of dietary flavonoids through their diet, for making them viable substitutes for conventional medicinal drugs.•Functional characterization and novel interactions between different types of dietary flavonoids with G-quadruplexes has been explored.•Interactions between G-quadruplex DNA structures and dietary flavonoids studied as potential molecular targets for prospective disease control.•Enlighten the structural variation between dietary flavonoids with respect to their binding to G-quadruplex DNA structures for providing knowledge that can be used to develop novel drugs for next-generation disease managements.
Interaction of Metal Complexes with G-Quadruplex DNA Georgiades, Savvas N; Abd Karim, Nurul H; Suntharalingam, Kogularamanan ...
Angewandte Chemie (International ed.),
June 1, 2010, Volume:
49, Issue:
24
Journal Article
Peer reviewed
Guanine-rich sequences of DNA can assemble into tetrastranded structures known as G-quadruplexes. It has been suggested that these secondary DNA structures could be involved in the regulation of ...several key biological processes. In the human genome, guanine-rich sequences with the potential to form G-quadruplexes exist in the telomere as well as in promoter regions of certain oncogenes. The identification of these sequences as novel targets for the development of anticancer drugs has sparked great interest in the design of molecules that can interact with quadruplex DNA. While most reported quadruplex DNA binders are based on purely organic templates, numerous metal complexes have more recently been shown to interact effectively with this DNA secondary structure. This Review provides an overview of the important roles that metal complexes can play as quadruplex DNA binding molecules, highlighting the unique properties metals can confer to these molecules.
Guanine-rich DNA sequences may fold back into non-canonical four-stranded secondary structures termed as G-quadruplexes. The role of G-quadruplexes has already been well established in different ...diseases like cancer, neurological and viral disorders etc. Also, several small molecules have been reported, which can influence the involvement of G-quadruplexes either through stabilization or destabilization in the cellular environment. Growing statistics have associated G-quadruplex assemblies to a discrete biological process in vivo, including DNA replication, transcription, genomic stability, and epigenetic regulation. DNA G-quadruplex existence in human telomere is well recognized attractive target for anticancer drugs. G-quadruplex-interactive ligands have been known to prevent telomerase access as well as telomere capping. To the best of our understanding, the role of G-quadruplexes in virology, neuropharmacology, cancer progression and its treatment has not been discussed on a single platform till date. This review aims to enhance our knowledge regarding these magical sticky quadruplex structures, which have been quite significantly proved to be the part of many cellular processes along with their established in vivo existence. Understanding regarding stabilizing or destabilizing ligands of these multistranded guanine quadruplex structures might be proved as the facilitator of drug discovery process for many incurable diseases in future.
•G-quadruplexes play remarkable roles in cancer therapy, antiviral research and neuropharmacology.•Small molecules/ligands/proteins interact with G-quadruplex DNA to regulate the gene expression in several diseases.•Both stabilizing or destabilizing effect has been observed on G-quadruplex structure through these ligands.•Studying the interaction (stabilization or destabilization) on G-quadruplex is extremely important for exploring their biological roles.•Understanding G-quadruplex ligand interactions may facilitate the drug-discovery process even for many incurable diseases too.
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