Nucleotide Analogues as Probes for DNA and RNA Polymerases

Kuchta, Robert D.

doi:10.1002/9780470559277.ch090203

Cited by 14 publications

(10 citation statements)

References 74 publications

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“… 39 In addition to 5-medCTP, previous studies also demonstrated that many other modified NTPs can be incorporated into DNA and RNA during in vitro replication and transcription. 14 , 16 , 40 – 42 In this respect, these detectable endogenous modified NTPs can be theoretically incorporated into DNA and RNA, which may compromise the regulatory roles of modifications.…”

Section: Resultsmentioning

confidence: 99%

Modified nucleoside triphosphates exist in mammals

et al. 2018

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Section: Resultsmentioning

confidence: 99%

Modified nucleoside triphosphates exist in mammals

et al. 2018

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“…Nucleoside or nucleotide analogue is an important class of antiviral therapeutics [83]. It is a powerful tool for dissecting the mechanisms and functions of viral DNA and RNA polymerases [84,85]. This screening selected top-ranking compounds with better binding scores than control compounds for further analysis.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…Khasianine formed hydrogen bonding with a Gln997 side chain with a binding score of −7.1 kcal/mol (Figure 4C), while VER155008 was involved in making −8.7 Monensin [83]. It is a powerful tool for dissecting the mechanisms and functions of viral DNA and RNA polymerases [84,85]. This screening selected top-ranking compounds with better binding scores than control compounds for further analysis.…”

Section: Molecular Dockingmentioning

confidence: 99%

Structural Elucidation of Rift Valley Fever Virus L Protein towards the Discovery of Its Potential Inhibitors

et al. 2022

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Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes a significant clinical burden in domestic and wild ruminants. Major outbreaks of the virus occur in livestock, and contaminated animal products or arthropod vectors can transmit the virus to humans. The viral RNA-dependent RNA polymerase (RdRp; L protein) of the RVFV is responsible for viral replication and is thus an appealing drug target because no effective and specific vaccine against this virus is available. The current study reported the structural elucidation of the RVFV-L protein by in-depth homology modeling since no crystal structure is available yet. The inhibitory binding modes of known potent L protein inhibitors were analyzed. Based on the results, further molecular docking-based virtual screening of Selleckchem Nucleoside Analogue Library (156 compounds) was performed to find potential new inhibitors against the RVFV L protein. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analysis of these compounds was also performed. Besides, the binding mechanism and stability of identified compounds were confirmed by a 50 ns molecular dynamic (MD) simulation followed by MM/PBSA binding free energy calculations. Homology modeling determined a stable multi-domain structure of L protein. An analysis of known L protein inhibitors, including Monensin, Mycophenolic acid, and Ribavirin, provide insights into the binding mechanism and reveals key residues of the L protein binding pocket. The screening results revealed that the top three compounds, A-317491, Khasianine, and VER155008, exhibited a high affinity at the L protein binding pocket. ADME analysis revealed good pharmacodynamics and pharmacokinetic profiles of these compounds. Furthermore, MD simulation and binding free energy analysis endorsed the binding stability of potential compounds with L protein. In a nutshell, the present study determined potential compounds that may aid in the rational design of novel inhibitors of the RVFV L protein as anti-RVFV drugs.

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“…Cordycepin has been considered as a nucleoside analogue [ 4 ], which is able to be involved in the actions of DNA and/or RNA polymerases [ 17 ]. After entering into the cell, it becomes mono-, di-, and tri-phosphates of 3-deoxyadenosine [ 18 ].…”

Section: An Active Constituent Of Cordyceps Cmentioning

confidence: 99%

The Anticancer Properties of Cordycepin and Their Underlying Mechanisms

Yoon

Park

2018

IJMS

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Cordyceps is a genus of ascomycete fungi that has been used for traditional herbal remedies. It contains various bioactive ingredients including cordycepin. Cordycepin, also known as 3-deoxyadenosine, is a major compound and has been suggested to have anticancer potential. The treatment of various cancer cells with cordycepin in effectively induces cell death and retards their cancerous properties. However, the underlying mechanism is not fully understood. Recent evidence has shed light on the molecular pathways involving cysteine-aspartic proteases (caspases), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase 3 beta (GSK-3β). Furthermore, the pathways are mediated by putative receptors, such as adenosine receptors (ADORAs), death receptors (DRs), and the epidermal growth factor receptor (EGFR). This review provides the molecular mechanisms by which cordycepin functions as a singular or combinational anticancer therapeutic agent.

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Nucleotide Analogues as Probes for DNA and RNA Polymerases

Cited by 14 publications

References 74 publications

Modified nucleoside triphosphates exist in mammals

Modified nucleoside triphosphates exist in mammals

Structural Elucidation of Rift Valley Fever Virus L Protein towards the Discovery of Its Potential Inhibitors

The Anticancer Properties of Cordycepin and Their Underlying Mechanisms

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