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.

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.  

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.

scholarly journals Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 198
Author(s):  
Lijun Lang ◽  
Alberto Perez
Keyword(s):  
Bayesian Inference ◽  
Virtual Screening ◽  
Statistical Mechanics ◽  
Small Molecules ◽  
Rational Design ◽  
Driving Forces ◽  
Peptide Inhibitors ◽  
Atomistic Simulations ◽  
Binding Mechanism ◽  
Intrinsically Disordered

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).

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