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.

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 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 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 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.

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1(MCL1)

2019 ◽  
Author(s):  
James Papatzimas ◽  
Evgueni Gorobets ◽  
Ranjan Maity ◽  
Mir Ishruna Muniyat ◽  
Justin L. MacCallum ◽  
...  
Keyword(s):  
Small Molecules ◽  
E3 Ligase ◽  
Myeloid Cell ◽  
Cell Leukemia ◽  
New Class ◽  
Apoptotic Protein ◽  
Family Protein ◽  
Ubiquitination Pathway

<div> <div> <div> <p>Here we show the development of heterobifunctional small molecules capable of selectively targeting MCL1 using a Proteolysis Targeting Chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon (CRBN) ubiquitination pathway, making these PROTACs a first step toward a new class of anti-apoptotic BCL-2 family protein degraders. </p> </div> </div> </div>

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

scholarly journals Radical cation transfer in a guanine pair: an insight to the G-quadruplex structure role using constrained DFT/MM

2021 ◽  
Vol 140 (7) ◽  
Author(s):  
Ranjitha Ravindranath ◽  
Padmabati Mondal ◽  
Natacha Gillet
Keyword(s):  
Radical Cation ◽  
Quadruplex Structure ◽  
G Quadruplex
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