scholarly journals Developing Novel G-Quadruplex Ligands: from Interaction with Nucleic Acids to Interfering with Nucleic Acid–Protein Interaction

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 396 ◽  
Author(s):  
Zhi-Yin Sun ◽  
Xiao-Na Wang ◽  
Sui-Qi Cheng ◽  
Xiao-Xuan Su ◽  
Tian-Miao Ou
Keyword(s):  
Dna Damage ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Related Protein ◽  
Damage Repair ◽  
Acid Protein ◽  
G Quadruplex ◽  
Tumor Drugs ◽  
The Relationship

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.

scholarly journals Nucleic acid protein crystallography facilitated by selenium nucleic acids (SeNA)

2019 ◽  
Vol 75 (a1) ◽  
pp. a158-a158
Author(s):  
Zhen Huang ◽  
Andrey Kovalevsky ◽  
Qianwei Zhao ◽  
Lillian Hu
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Protein Crystallography ◽  
Acid Protein

scholarly journals How ‘Protein-Docking’ Translates into the New Emerging Field of Docking Small Molecules to Nucleic Acids?

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2749
Author(s):  
Francesca Tessaro ◽  
Leonardo Scapozza
Keyword(s):  
Molecular Docking ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Mrna Level ◽  
Protein Docking ◽  
Structural Nature ◽  
Rigid Docking

In this review, we retraced the ‘40-year evolution’ of molecular docking algorithms. Over the course of the years, their development allowed to progress from the so-called ‘rigid-docking’ searching methods to the more sophisticated ‘semi-flexible’ and ‘flexible docking’ algorithms. Together with the advancement of computing architecture and power, molecular docking’s applications also exponentially increased, from a single-ligand binding calculation to large screening and polypharmacology profiles. Recently targeting nucleic acids with small molecules has emerged as a valuable therapeutic strategy especially for cancer treatment, along with bacterial and viral infections. For example, therapeutic intervention at the mRNA level allows to overcome the problematic of undruggable proteins without modifying the genome. Despite the promising therapeutic potential of nucleic acids, molecular docking programs have been optimized mostly for proteins. Here, we have analyzed literature data on nucleic acid to benchmark some of the widely used docking programs. Finally, the comparison between proteins and nucleic acid targets docking highlighted similarity and differences, which are intrinsically related to their chemical and structural nature.

scholarly journals Nucleic Acid Immunity and DNA Damage Response: New Friends and Old Foes

2021 ◽  
Vol 12 ◽  
Author(s):  
Clara Taffoni ◽  
Alizée Steer ◽  
Johanna Marines ◽  
Hanane Chamma ◽  
Isabelle K. Vila ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Dna Damage Response ◽  
Immune Activation ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Fine Tuning ◽  
Innate Immune Activation ◽  
Damage Response

The maintenance of genomic stability in multicellular organisms relies on the DNA damage response (DDR). The DDR encompasses several interconnected pathways that cooperate to ensure the repair of genomic lesions. Besides their repair functions, several DDR proteins have emerged as involved in the onset of inflammatory responses. In particular, several actors of the DDR have been reported to elicit innate immune activation upon detection of cytosolic pathological nucleic acids. Conversely, pattern recognition receptors (PRRs), initially described as dedicated to the detection of cytosolic immune-stimulatory nucleic acids, have been found to regulate DDR. Thus, although initially described as operating in specific subcellular localizations, actors of the DDR and nucleic acid immune sensors may be involved in interconnected pathways, likely influencing the efficiency of one another. Within this mini review, we discuss evidences for the crosstalk between PRRs and actors of the DDR. For this purpose, we mainly focus on cyclic GMP-AMP (cGAMP) synthetase (cGAS) and Interferon Gamma Inducible Protein 16 (IFI16), as major PRRs involved in the detection of aberrant nucleic acid species, and components of the DNA-dependent protein kinase (DNA-PK) complex, involved in the repair of double strand breaks that were recently described to qualify as potential PRRs. Finally, we discuss how the crosstalk between DDR and nucleic acid-associated Interferon responses cooperate for the fine-tuning of innate immune activation, and therefore dictate pathological outcomes. Understanding the molecular determinants of such cooperation will be paramount to the design of future therapeutic approaches.

scholarly journals Nucleic Acid Oxidation in DNA Damage Repair and Epigenetics

2014 ◽  
Vol 114 (8) ◽  
pp. 4602-4620 ◽  
Author(s):  
Guanqun Zheng ◽  
Ye Fu ◽  
Chuan He
Keyword(s):  
Dna Damage ◽  
Nucleic Acid ◽  
Dna Damage Repair ◽  
Acid Oxidation ◽  
Damage Repair

scholarly journals A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids

2020 ◽  
Vol 8 (37) ◽  
pp. 8558-8572
Author(s):  
Sudhakar Godeshala ◽  
Bhavani Miryala ◽  
Subhadeep Dutta ◽  
Matthew D. Christensen ◽  
Purbasha Nandi ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Small Molecule ◽  
Nucleic Acid Delivery ◽  
Small Molecule Drug

A library of lipopolymer nanoparticles for nucleic acid, small-molecule drug, and simultaneous drug and nucleic acid delivery.

scholarly journals Exogenous damage causes cell DNA damage through mediated reactive oxygen levels

2019 ◽  
Vol 131 ◽  
pp. 01018
Author(s):  
Peiyan Guo ◽  
Ning Ma ◽  
Jingbo Shan ◽  
Techang Chen ◽  
Yujie Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Recognition Mechanism ◽  
Exogenous Dna ◽  
Damage Recognition ◽  
Damage Repair ◽  
Intracellular Ros ◽  
Accumulation Of Damage ◽  
Tumor Drugs

Many anti-tumor drugs can induce tumor apoptosis by increasing intracellular ROS. In the present study, we build a model which did not directly cause DNA damage, but simulated damage products. The model of this injury was transferred into the cell so that the cell’s damage recognition mechanism mistakenly recognized that its own DNA was damaged, which in turn induced a response. Based on this model, the damaged plasmids (exogenous DNA damage) were transferred into the cells and the amount of reactive oxygen in the cells was improved, and DNA damage of the cells was increased. Therefore, exogenous DNA damage can affect the accumulation of damage in cells by affecting the level of reactive oxygen species, which provides a reference for DNA damage repair research.

scholarly journals Energy Transfer as A Driving Force in Nucleic Acid–Protein Interactions

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1443
Author(s):  
Zavyalova ◽  
Kopylov
Keyword(s):  
Energy Transfer ◽  
Nucleic Acid ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Protein Structures ◽  
Quantitative Structure Activity Relationship ◽  
Efficient Energy Transfer ◽  
Acid Protein ◽  
G Quadruplex ◽  
Interface Organization

Many nucleic acid–protein structures have been resolved, though quantitative structure-activity relationship remains unclear in many cases. Thrombin complexes with G-quadruplex aptamers are striking examples of a lack of any correlation between affinity, interface organization, and other common parameters. Here, we tested the hypothesis that affinity of the aptamer–protein complex is determined with the capacity of the interface to dissipate energy of binding. Description and detailed analysis of 63 nucleic acid–protein structures discriminated peculiarities of high-affinity nucleic acid–protein complexes. The size of the amino acid sidechain in the interface was demonstrated to be the most significant parameter that correlates with affinity of aptamers. This observation could be explained in terms of need of efficient energy transfer from interacting residues. Application of energy dissipation theory provided an illustrative tool for estimation of efficiency of aptamer–protein complexes. These results are of great importance for a design of efficient aptamers.

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