scholarly journals G-Quadruplex targeting ligands: A hope and a new horizon in Cancer Therapeutics

2018 ◽  
Author(s):  
Nilanjan Banerjee ◽  
Suman Panda ◽  
Subhrangsu Chatterjee
Keyword(s):  
Secondary Structure ◽  
Cancer Treatment ◽  
Small Molecules ◽  
Human Genome ◽  
Cancer Therapeutics ◽  
Structural Diversity ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Therapeutic Research ◽  
Widespread Interest

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 G-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.

Up- and downregulation of mature miR-1587 function by modulating its G-quadruplex structure and using small molecules

2019 ◽  
Vol 121 ◽  
pp. 127-134 ◽  
Author(s):  
Fangyuan Li ◽  
Wei Tan ◽  
Han Chen ◽  
Jiang Zhou ◽  
Ming Xu ◽  
...  
Keyword(s):  
Small Molecules ◽  
Quadruplex Structure ◽  
G Quadruplex

scholarly journals Recent Progress of Targeted G-Quadruplex-Preferred Ligands Toward Cancer Therapy

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 429 ◽  
Author(s):  
Sefan Asamitsu ◽  
Shunsuke Obata ◽  
Zutao Yu ◽  
Toshikazu Bando ◽  
Hiroshi Sugiyama
Keyword(s):  
Nucleic Acid ◽  
Secondary Structure ◽  
Recent Progress ◽  
Development Process ◽  
Protein Targeting ◽  
Molecular Probe ◽  
Drug Development Process ◽  
Quadruplex Structure ◽  
G4 Dna ◽  
G Quadruplex

A G-quadruplex (G4) is a well-known nucleic acid secondary structure comprising guanine-rich sequences, and has profound implications for various pharmacological and biological events, including cancers. Therefore, ligands interacting with G4s have attracted great attention as potential anticancer therapies or in molecular probe applications. To date, a large variety of DNA/RNA G4 ligands have been developed by a number of laboratories. As protein-targeting drugs face similar situations, G-quadruplex-interacting drugs displayed low selectivity to the targeted G-quadruplex structure. This low selectivity could cause unexpected effects that are usually reasons to halt the drug development process. In this review, we address the recent research on synthetic G4 DNA-interacting ligands that allow targeting of selected G4s as an approach toward the discovery of highly effective anticancer drugs.

Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent

2016 ◽  
Vol 12 (8) ◽  
pp. 2506-2518 ◽  
Author(s):  
Soma Mondal ◽  
Jagannath Jana ◽  
Pallabi Sengupta ◽  
Samarjit Jana ◽  
Subhrangsu Chatterjee
Keyword(s):  
Small Molecules ◽  
Anticancer Agent ◽  
New Class ◽  
Quadruplex Structure ◽  
Mechanistic Approach ◽  
G Quadruplex ◽  
Anticancer Therapeutics ◽  
Potential Strategy

The use of small molecules to arrest G-quadruplex structure has become a potential strategy for the development and design of a new class of anticancer therapeutics.

scholarly journals Engineering yellow fluorescent protein probe for visualization of parallel DNA G-quadruplex

2018 ◽  
Vol 21 (3) ◽  
pp. 84-89 ◽  
Author(s):  
Tuom TT Truong ◽  
Trang PT Phan ◽  
Linh TT Le ◽  
Dung H Nguyen ◽  
Hoang D Nguyen ◽  
...  
Keyword(s):  
Small Molecules ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Biological Processes ◽  
Naked Eye ◽  
High Affinity ◽  
Quadruplex Structure ◽  
G Quadruplex

Introduction: The formation of G-quadruplex plays a key role in many biological processes. Therefore, visualization of G-quadruplex is highly essential for design of G-quadruplex-targeted small molecules (drugs). Herein, we report on an engineered fluorescent protein probe which was able to distinguish G-quadruplex topologies. Methods: The fluorescent protein probe was generated by genetically incorporating yellow fluorescent protein (YFP) to RNA helicase associated with AU-rich element (RHAU) peptide motif. Results: This probe could selectively bind and visualize parallel G-quadruplex structure (T95-2T) at high affinity (Kd~130 nM). Visualization of the parallel G-quadruplex by RHAU-YFP could be easily observed in vitro by using normal Gel Doc or the naked eye. Conclusion: The YFP probe could be encoded in cells to provide a powerful tool for detection of parallel G-quadruplexes both in vitro and in vivo.  

scholarly journals Restriction of telomerase capping by short non-toxic peptides via arresting telomeric G-quadruplex

RSC Advances ◽  
2017 ◽  
Vol 7 (34) ◽  
pp. 20888-20899 ◽  
Author(s):  
Jagannath Jana ◽  
Pallabi Sengupta ◽  
Soma Mondal ◽  
Subhrangsu Chatterjee
Keyword(s):  
Cancer Therapeutics ◽  
Telomeric Dna ◽  
Quadruplex Structure ◽  
Promising Strategy ◽  
G Quadruplex ◽  
Toxic Peptides

The stabilization of a G-quadruplex structure in human telomeric DNA has become a promising strategy in the development of cancer therapeutics.

scholarly journals In Silico Screening and Binding Characterization of Small Molecules toward a G-Quadruplex Structure Formed in the Promoter Region ofc-MYCOncogene

ACS Omega ◽  
2017 ◽  
Vol 2 (8) ◽  
pp. 4382-4397 ◽  
Author(s):  
Jyotsna Bhat ◽  
Soma Mondal ◽  
Pallabi Sengupta ◽  
Subhrangsu Chatterjee
Keyword(s):  
Small Molecules ◽  
In Silico ◽  
Promoter Region ◽  
In Silico Screening ◽  
Quadruplex Structure ◽  
G Quadruplex

Study of the binding mechanism between aptamer GO18-T-d and gonyautoxin 1/4 by molecular simulation

2016 ◽  
Vol 18 (34) ◽  
pp. 23458-23461 ◽  
Author(s):  
Shunxiang Gao ◽  
Bo Hu ◽  
Xin Zheng ◽  
Dejing Liu ◽  
Mingjuan Sun ◽  
...  
Keyword(s):  
Small Molecules ◽  
Molecular Simulation ◽  
Molecular Diagnostics ◽  
Complex Structures ◽  
Binding Mechanism ◽  
Therapeutic Application ◽  
Induced Fit ◽  
Quadruplex Structure ◽  
G Quadruplex

GTX1/4 can induce the formation of an antiparallel G-quadruplex structure in aptamer GO18-T-d and combine steadily in the groove at the top of the G-quadruplex structure. The complex structures and special induced fit mechanism between aptamer and small molecules provide a reference for aptamer development in molecular diagnostics and therapeutic application.

Recognition of an important G-quadruplex in the HIV-1 promoter with natural small molecules

2016 ◽  
Vol 94 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Weixuan Wang ◽  
Yang Sui ◽  
Lulu Zhang ◽  
Wei Tan ◽  
Xiangwei He ◽  
...  
Keyword(s):  
Small Molecules ◽  
Ionization Mass ◽  
Binding Affinities ◽  
Quadruplex Structure ◽  
Novel Approach ◽  
G Quadruplex ◽  
Before And After ◽  
Anti Hiv ◽  
Thermal Stability Of ◽  
Hiv 1

Targeting a G-quadruplex with chemical small molecules is a useful strategy for gene therapy for disease. The guanine-rich sequence d(5′-TG1G2CCTG3G4G5CG6G7G8ACTG9G10G11-3′) in the HIV-1 promoter can form a G-quadruplex structure. In this study, circular dichroism was performed to study the conformation and thermal stability of the HIV-1 G-quadruplex before and after adding small molecules. A DMS footprinting assay was used to identify which guanosine can be integrated into the G-quadruplex structure. Electrospray ionization mass spectrometry was used to evaluate the binding affinities of the small molecules with the G-quadruplex. Our results showed that G1, G2, G3, G4, G7, G8, G9, and G10 of the above oligonucleotides formed a two G-tetrad antiparallel G-quadrulex, and nitidine chloride was found to have the highest binding affinity toward the HIV-1 G-quadruplex among the eight studied small molecules. The Tm value of the G-quadruplex was enhanced from 56.6 to 63.2 °C when fourfold nitidine chloride was added. This is potentially a novel approach for anti-HIV-1 drug development.

scholarly journals The role of G-quadruplex/i-motif secondary structures as cis-acting regulatory elements

2010 ◽  
Vol 82 (8) ◽  
pp. 1609-1621 ◽  
Author(s):  
Samantha Kendrick ◽  
Laurence H. Hurley
Keyword(s):  
Secondary Structure ◽  
Small Molecules ◽  
Dynamic Equilibrium ◽  
Double Helix ◽  
Regulatory Elements ◽  
Cis Acting ◽  
Secondary Structure Formation ◽  
G Quadruplex ◽  
Intracellular Proteins

The nature of DNA has captivated scientists for more than 50 years. The discovery of the double-helix model of DNA by Watson and Crick in 1953 not only established the primary structure of DNA, but also provided the mechanism behind DNA function. Since then, researchers have continued to further the understanding of DNA structure and its pivotal role in transcription. The demonstration of DNA secondary structure formation has allowed for the proposal that the dynamics of DNA itself can function to modulate transcription. This review presents evidence that DNA can exist in a dynamic equilibrium between duplex and secondary conformations. In addition, data demonstrating that intracellular proteins as well as small molecules can shift this equilibrium in either direction to alter gene transcription will be discussed, with a focus on the modulation of proto-oncogene expression.

scholarly journals Alternative approaches to target Myc for cancer treatment

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chen Wang ◽  
Jiawei Zhang ◽  
Jie Yin ◽  
Yichao Gan ◽  
Senlin Xu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Small Molecules ◽  
Drug Target ◽  
The Past ◽  
Physiological Processes ◽  
Alternative Approaches ◽  
Global Transcriptome ◽  
Factor C ◽  
Signaling Modules ◽  
Druggable Targets

AbstractThe Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL, which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc, respectively. Myc protein orchestrates diverse physiological processes, including cell proliferation, differentiation, survival, and apoptosis. Myc modulates about 15% of the global transcriptome, and its deregulation rewires the cellular signaling modules inside tumor cells, thereby acquiring selective advantages. The deregulation of Myc occurs in >70% of human cancers, and is related to poor prognosis; hence, hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades. Nevertheless, no specific drug is currently available to directly target Myc, mainly because of its “undruggable” properties: lack of enzymatic pocket for conventional small molecules to bind; inaccessibility for antibody due to the predominant nucleus localization of Myc. Although the topic of targeting Myc has actively been reviewed in the past decades, exciting new progresses in this field keep emerging. In this review, after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer, we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.

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