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51.
Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase
Dr. Simone Vitiello Dr. Monica Caselli Dr. Giorgia Pavesi Dr. Matteo Santucci Dr. Stefania Ferrari Prof. Maria Paola Costi Prof. Glauco Ponterini 《Chembiochem : a European journal of chemical biology》2021,22(10):1800-1810
The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided. 相似文献
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53.
Paola Riolo Roxana L. Minuz Gianfranco Anfora Marco V. Rossi Stacconi Silvia Carlin Nunzio Isidoro Roberto Romani 《Journal of chemical ecology》2012,38(8):1017-1030
The Palearctic planthopper Hyalesthes obsoletus is the natural vector of the grapevine yellow disease Bois noir. Grapevine is an occasional host plant of this polyphagous planthopper. To deepen our knowledge of the role of plant volatile organic compounds for H. obsoletus host plant searching, we carried out behavioral, morphological, and electrophysiological studies. We tested the attraction of H. obsoletus to nettle, field bindweed, hedge bindweed, chaste tree, and grapevine by using a Y-shaped olfactometer. The results showed a significant attraction of male H. obsoletus to chaste tree, and of the females to nettle. Male H. obsoletus were repelled by odor from hedge bindweed. Ultrastructural studies of the antennae showed at least two types of olfactory sensilla at the antennal pedicel: plaque organs and trichoid sensilla. Volatile organic compounds from nettle and chaste tree were collected, and the extracts were analyzed by coupling gas-chromatography to both mass-spectrometry and electroantennography. The volatile organic compounds that elicited electrophysiological responses in male and female antennae were identified. These findings are discussed with respect to behavior of H. obsoletus males and females in the field. 相似文献
54.
Salvatore Mirabile Dr. Serena Vittorio Prof. Maria Paola Germanò Dr. Ilenia Adornato Dr. Laura Ielo Prof. Antonio Rapisarda Prof. Rosaria Gitto Francesca Pintus Dr. Antonella Fais Prof. Laura De Luca 《ChemMedChem》2021,16(19):3083-3093
There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC50=0.18 μM) that proved to be ∼100-fold more active than reference compound kojic acid (IC50=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR. 相似文献
55.
Natalia Brossard Beatriz Gonzalez-Muñoz Carolina Pavez Arianna Ricci Xinmiao Wang Fernando Osorio Edmundo Bordeu Giuseppina Paola Parpinello Jianshe Chen 《International Journal of Food Science & Technology》2021,56(10):5382-5394
Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication. 相似文献
56.
We investigate the performance of the Mimetic Finite Difference (MFD) method for the approximation of a constraint optimal control problem governed by an elliptic operator. Low-order and high-order mimetic discretizations are considered and a priori error estimates are derived, in a suitable discrete norm, for both the control and the state variables. A wide class of numerical experiments performed on a set of examples selected from the literature assesses the robustness of the MFD method and confirms the convergence analysis. 相似文献
57.
Pedrini Matteo Langella Valentina Battaglia Mario Alberto Zaratin Paola 《Scientometrics》2018,114(3):1227-1250
Scientometrics - In recent year, a growing attention is dedicated to the assessment of research’s social impact. While prior research has often dealt with results of research, the last decade... 相似文献
58.
Paola Pellegrini Franco Mascia Thomas Stützle Mauro Birattari 《Soft Computing - A Fusion of Foundations, Methodologies and Applications》2014,18(11):2177-2190
In this paper, we assess the sensitivity of reactive tabu search to its meta-parameters. Based on a thorough experimental analysis of reactive tabu search applications to the quadratic assignment and the maximum clique problem, we show that its performance is relatively insensitive to its meta-parameters. This is particularly evident when compared to the sensitivity of tabu search to its parameters: tabu search is rather penalized if used with sub-optimal parameter settings. Reactive tabu search does not strongly pay its high parameter robustness in terms of performance, although it does not improve the peak performance of tabu search. 相似文献
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60.
Adele Chimento Anna Santarsiero Domenico Iacopetta Jessica Ceramella Arianna De Luca Vittoria Infantino Ortensia Ilaria Parisi Paola Avena Maria Grazia Bonomo Carmela Saturnino Maria Stefania Sinicropi Vincenzo Pezzi 《International journal of molecular sciences》2021,22(10)
Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer. 相似文献