Fullerene derivatives as a new class of inhibitors of protein tyrosine phosphatases

Kobzar, Oleksandr; Trush, Viacheslav V.; Tanchuk, Vsevolod Yu.; Zhilenkov, Alexander V.; Troshin, Pavel A.; Vovk, А. I.

doi:10.1016/j.bmcl.2014.04.110

Cited by 25 publications

(10 citation statements)

References 69 publications

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“… 23 , 24 As a result, fullerene and its derivatives have been utilized as inhibitors for certain proteins like neuronal nitric oxide synthase, 25 human immunodeficiency virus protease, 26 glutathione reductase, 27 and tyrosine phosphatases. 28 Studies on fullerene are, however, limited due to its poor solubility in aqueous medium. In aqueous solution, it has a solubility of less than 10 –9 mg/L with an octanol–water partition coefficient log K OW of 6.67 and readily forms aggregates of n C 60 , thereby making it sparingly soluble in water.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Inhibitory and Antioxidant Effects of Fullerene and Fullerenol on Ribonuclease A

et al. 2018

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Fullerene–protein interaction studies have been a key topic of investigation in recent times, but the lower water solubility of fullerene somewhat limits its application in the biological system. In this work, we have compared the activities of fullerene and its water-soluble hydrated form, that is fullerenol, on ribonuclease A (RNase A) under physiological conditions (pH 7.4). The interaction studies of fullerene and fullerenol with protein suggest that the binding depends on the hydrophobic interactions between the protein and the ligand. In addition, fullerene and fullerenol slow down the ribonucleolytic activity of RNase A through noncompetitive and mixed types of inhibition, respectively. This precisely gives the idea about the ligand-binding sites in RNase A, which has further been explored using docking studies. Both these nanoparticles show a reduction in dityrosine formation in RNase A caused due to oxidative stress and also prevent RNase A dimer formation to different extents depending on their concentration.

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Section: Introductionmentioning

confidence: 99%

Exploring the Inhibitory and Antioxidant Effects of Fullerene and Fullerenol on Ribonuclease A

et al. 2018

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“…Since that time our laboratory has produced several fullerene amino acids [23][24][25] and peptide derivatives [26,27] to investigate their cellular penetrating properties [28,29], their transport through skin [30], their inhibition of neuroblastoma [26], and their ability to inhibit carbonic anhydrase [31]. Others have investigated the cytotoxicity, DNA cleavage, and enzyme inhibition by fullerene amino acids, peptides, and other C 60 derivatives [32][33][34][35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Fullerene-based inhibitors of HIV-1 protease

et al. 2015

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A series of Fmoc-Phe(4-aza-C60)-OH of fullerene amino acid derived peptides have been prepared by solid phase peptide synthesis, in which the terminal amino acid, Phe(4-aza-C60)-OH, is derived from the dipolar addition to C60 of the Fmoc-Nα-protected azido amino acids derived from phenylalanine: Fmoc-Phe(4-aza-C60)-Lys3-OH (1), Fmoc-Phe(4-aza-C60)-Pro-Hyp-Lys-OH (2), and Fmoc-Phe(4-aza-C60)-Hyp-Hyp-Lys-OH (3). The inhibition constant of our fullerene aspartic protease PRIs utilized FRET-based assay to evaluate the enzyme kinetics of HIV-1 PR at various concentrations of inhibitors. Simulation of the docking of the peptide Fmoc-Phe-Pro-Hyp-Lys-OH overestimated the inhibition, while the amino acid PRIs were well estimated. The experimental results show that C60-based amino acids are a good base structure in the design of protease inhibitors and that their inhibition can be improved upon by the addition of designer peptide sequences.

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“…Fullerene derivative with 2-(3-phenylpropyl)malonic acid-based addends homological to compound FF1 demonstrated prolonged antioxidant activity in vitro [ 15 ]. Additionally, a fullerene functionalized with eight residues of 3-phenylpropanoic acid was reported as an efficient tyrosine phosphatase inhibitor with IC 50 values in the high nanomolar range [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Functionalized Fullerenes on ROS Homeostasis Determine Their Cytoprotective or Cytotoxic Properties

et al. 2020

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Background: Functionalized fullerenes (FF) can be considered regulators of intracellular reactive oxygen species (ROS) homeostasis; their direct oxidative damage—as well as regulation of oxidant enzymes and signaling pathways—should be considered. Methods: Uptake of two water-soluble functionalized C70 fullerenes with different types of aromatic addends (ethylphenylmalonate and thienylacetate) in human fetal lung fibroblasts, intracellular ROS visualization, superoxide scavenging potential, NOX4 expression, NRF2 expression, oxidative DNA damage, repair genes, cell proliferation and cell cycle were studied. Results & conclusion: The intracellular effects of ethylphenylmalonate C70 derivative (FF1) can be explained in terms of upregulated NOX4 activity. The intracellular effects of thienylacetate C70 derivative (FF2) can be probably resulted from its superoxide scavenging potential and inhibition of lipid peroxidation. FF1 can be considered a NOX4 upregulator and potential cytotoxicant and FF2, as a superoxide scavenger and a potential cytoprotector.

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Fullerene derivatives as a new class of inhibitors of protein tyrosine phosphatases

Cited by 25 publications

References 69 publications

Exploring the Inhibitory and Antioxidant Effects of Fullerene and Fullerenol on Ribonuclease A

Exploring the Inhibitory and Antioxidant Effects of Fullerene and Fullerenol on Ribonuclease A

Fullerene-based inhibitors of HIV-1 protease

Effects of Functionalized Fullerenes on ROS Homeostasis Determine Their Cytoprotective or Cytotoxic Properties

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