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241.
Matteo Moretti Isabella Marzi Cristina Cantarutti Mirella Vivoli Vega Walter Mandaliti Maria Chiara Mimmi Francesco Bemporad Alessandra Corazza Fabrizio Chiti 《Molecules (Basel, Switzerland)》2022,27(13)
TAR DNA-binding protein 43 (TDP-43) forms intraneuronal cytoplasmic inclusions associated with amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. Its N-terminal domain (NTD) can dimerise/oligomerise with the head-to-tail arrangement, which is essential for function but also favours liquid-liquid phase separation and inclusion formation of full-length TDP-43. Using various biophysical approaches, we identified an alternative conformational state of NTD in the presence of Sulfobetaine 3-10 (SB3-10), with higher content of α-helical structure and tryptophan solvent exposure. NMR shows a highly mobile structure, with partially folded regions and β-sheet content decrease, with a concomitant increase of α-helical structure. It is monomeric and reverts to native oligomeric NTD upon SB3-10 dilution. The equilibrium GdnHCl-induced denaturation shows a cooperative folding and a somewhat lower conformational stability. When the aggregation processes were compared with and without pre-incubation with SB3-10, but at the identical final SB3-10 concentration, a slower aggregation was found in the former case, despite the reversible attainment of the native conformation in both cases. This was attributed to protein monomerization and oligomeric seeds disruption by the conditions promoting the alternative conformation. Overall, the results show a high plasticity of TDP-43 NTD and identify strategies to monomerise TDP-43 NTD for methodological and biomedical applications. 相似文献
242.
Marília Vilela Salvador Flvio Vinícius Crizstomo Kock Isabella Laporte Santos Jean Fausto Carvalho Paulino Calo Panhoca de Almeida Rodrigo Henrique dos Santos Garcia Luciana Lasry Benchimol-Reis Luiz Alberto Colnago Antonio Gilberto Ferreira 《Molecules (Basel, Switzerland)》2022,27(7)
The use of UV-C cool white light on bean (Phaseolus vulgaris L.) seeds significantly increases the biochemical seed coat post-harvest darkening process, whilst preserving seed germination. The aim of this work consists in monitoring the effect caused by the incidence of UV-C light on different bean genotypes using NMR spectroscopy. The genotype samples named IAC Alvorada; TAA Dama; BRS Estilo and BRS Pérola from the Agronomic Institute (IAC; Campinas; SP; Brazil) were evaluated. The following two methodologies were used: a prolonged darkening, in which the grain is placed in a room at a controlled temperature (298 K) and humidity for 90 days, simulating the supermarket shelf; an accelerated darkening, where the grains are exposed to UV-C light (254 nm) for 96 h. The experiments were performed using the following innovative time-domain (TD) NMR approaches: the RK-ROSE pulse sequence; one- and two-dimensional high resolution (HR) NMR experiments (1H; 1H-1H COSY and 1H-13C HSQC); chemometrics tools, such as PLS-DA and heat plots. The results suggest that the observed darkening occurs on the tegument after prolonged (90 days) and accelerated (96 h) conditions. In addition, the results indicate that phenylalanine is the relevant metabolite within this context, being able to participate in the chemical reactions accounted for by the darkening processes. Additionally, it is possible to confirm that a UV-C lamp accelerates oxidative enzymatic reactions and that the NMR methods used were a trustworthy approach to monitor and understand the darkening in bean seeds at metabolite level. 相似文献
243.
Umpolung strategies, defined as synthetic approaches which reverse commonly accepted reactivity patterns, are broadly recognized as enabling tools for small molecule synthesis and catalysis. However, methods which exploit this logic for peptide and protein functionalizations are comparatively rare, with the overwhelming majority of existing bioconjugation approaches relying on the well-established reactivity profiles of a handful of amino acids. This perspective serves to highlight a small but growing body of recent work that masterfully capitalizes on the concept of polarity reversal for the selective modification of proteinogenic functionalities. Current applications of umpolung chemistry in organic synthesis and chemical biology as well as the vast potential for further innovations in peptide and protein modification will be discussed.This perspective highlights the growing body of literature that leverages polarity reversal (umpolung reactivity) for the selective modification of proteinogenic functionalities and identifies opportunities for further innovation. 相似文献
244.
Nayara Júnia de Souza Bontempo Drielly Aparecida Paixo Paula Marynella Alves Pereira Lima Deysse Carla Tolentino Barros Dayanne Silva Borges Priscila Capelari Orsolin Isabella Castro Martins Pedro Henrique Alves Machado Ricardo Campos Lino Tiago Rodrigues de Souza Luana Munique Sousa Ramos Samuel Cota Teixeira Raoni Pais Siqueira Luiz Ricardo Goulart Filho Wendell Guerra Robson Jos de Oliveira Júnior Thaise Gonalves de Araújo 《Molecules (Basel, Switzerland)》2022,27(20)
Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa. 相似文献
245.
Thomas Scattolin Sonia Giust Paola Bergamini Isabella Caligiuri Luciano Canovese Nicola Demitri Roberto Gambari Ilaria Lampronti Flavio Rizzolio Fabiano Visentin 《应用有机金属化学》2019,33(6)
A complete protocol for the synthesis of new palladacyclopentadienyl complexes with purine‐based carbenes as supporting ligands is described. The new organometallic compounds were exhaustively characterized using NMR and infrared spectroscopies and elemental analysis. The single‐crystal X‐ray structure of complex 2b coordinating also a triphenylphosphine was resolved. Some of these complexes showed an antiproliferative activity comparable to or better than that of cisplatin on two human ovarian cancer lines: A2780 (cisplatin‐sensitive) and A2780cis (cisplatin‐resistant). Moreover, for complexes 2 and 3 (coordinating one purine‐based N‐heterocyclic carbene ligand and one phosphine) the cytotoxicity is associated with an evident induction of apoptosis. Finally, complexes 3 , bearing one purine‐based N‐heterocyclic carbene ligand and one 1,3,5‐triaza‐7‐phosphaadamantane, proved practically inactive on non‐tumour fibroblast cells (MRC‐5). 相似文献
246.
247.
Dr. Laura Zanetti-Polzi Dr. Ryan Djemili Dr. Stéphanie Durot Prof. Valérie Heitz Prof. Isabella Daidone Dr. Barbara Ventura 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(72):17514-17524
The complexation processes of N,N’-dibutyl-1,4,5,8-naphthalene diimide ( NDI ) into two types of π-electron-rich molecular containers consisting of two Zn(II)-porphyrins connected by four flexible linkers of two different lengths, were characterized by means of absorption and emission spectroscopies and molecular dynamics simulation. Notably, the addition of NDI leads to a strong quenching of the fluorescence of both cages only when they are in an open conformation suitable for guest encapsulation, a situation triggered by silver(I) ions binding to the lateral triazoles. Molecular dynamics simulations confirm the fast binding of NDI , likely assisted by NDI -silver(I) interactions. Upon NDI complexation, the two porphyrin macrocycles get closer, with an optimized face to face orientation, suggesting an induced-fit mechanism through π–π interactions with the NDI aromatic cycle. Ultrafast transient absorption experiments allowed to identify the process of quenching of the Zn-porphyrin fluorescence as an efficient photoinduced electron transfer reaction between the cage porphyrin and the included NDI guest. The process occurs on fast and ultrafast time scales in the two complexes (1.5 ps and ≤300 fs) leading to a short-lived charge separated state (charge recombination lifetimes in the order of 30–40 ps). The combined computational and experimental approach used here is able to furnish a reliable model of the NDI -cage complexation mechanism and of the corresponding electron transfer reaction, attesting the allosteric control of both processes by the silver(I) ions. 相似文献
248.
Henry W. Orton Jan Stanek Tobias Schubeis Dylan Foucaudeau Claire Ollier Adrian W. Draney Tanguy Le Marchand Diane Cala‐De Paepe Isabella C. Felli Roberta Pierattelli Sebastian Hiller Wolfgang Bermel Guido Pintacuda 《Angewandte Chemie (International ed. in English)》2020,59(6):2380-2384
Narrow proton signals, high sensitivity, and efficient coherence transfers provided by fast magic‐angle spinning at high magnetic fields make automated projection spectroscopy feasible for the solid‐state NMR analysis of proteins. We present the first ultrahigh dimensional implementation of this approach, where 5D peak lists are reconstructed from a number of 2D projections for protein samples of different molecular sizes and aggregation states, which show limited dispersion of chemical shifts or inhomogeneous broadenings. The resulting datasets are particularly suitable to automated analysis and yield rapid and unbiased assignments of backbone resonances. 相似文献
249.
Fei Lu Julia Rodriguez-Garcia Isabella Van Damme Nicholas J. Westwood Liz Shaw James S. Robinson Geoff Warren Afroditi Chatzifragkou Simon McQueen Mason Leonardo Gomez Laura Faas Kelvin Balcombe Chittur Srinivasan Fiorella Picchioni Paul Hadley Dimitris Charalampopoulos 《Current Opinion in Green and Sustainable Chemistry》2018
250.
Isabella G. Alonso Lais T. Yamane Verônica S. de Freitas-Blanco Luiz F.T. Novaes Michelle Franz-Montan Eneida de Paula Marili V.N. Rodrigues Rodney A.F. Rodrigues Julio C. Pastre 《Tetrahedron》2018,74(38):5192-5199
A 5-step synthesis of spilanthol (affinin) is reported, where the route features complete control of alkene geometry during the assembling of the double bonds, with the use of a Sonogashira cross-coupling reaction, a Z-selective alkyne semi-reduction and a HWE olefination reaction as the key steps. A simplified analogue was also prepared in 4 steps. Both compounds were found to permeate dermatomed pig ear skin through an in vitro Franz-type diffusion cell. The simplified analogue presented a superior anesthetic effect in vivo, using the tail flick model, when compared to spilanthol and to the commercial standard EMLA®. These results suggest that both spilanthol and its analogue could be useful as a topical anesthetic in clinical practice. 相似文献