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排序方式: 共有99条查询结果,搜索用时 109 毫秒
1.
Andreas M. Küffner Miriam Linsenmeier Fulvio Grigolato Marc Prodan Remo Zuccarini Umberto Capasso Palmiero Lenka Faltova Paolo Arosio 《Chemical science》2021,12(12):4373
Biomolecular condensates are emerging as an efficient strategy developed by cells to control biochemical reactions in space and time by locally modifying composition and environment. Yet, local increase in protein concentration within these compartments could promote aberrant aggregation events, including the nucleation and growth of amyloid fibrils. Understanding protein stability within the crowded and heterogeneous environment of biological condensates is therefore crucial, not only when the aggregation-prone protein is the scaffold element of the condensates but also when proteins are recruited as client molecules within the compartments. Here, we investigate the partitioning and aggregation kinetics of the amyloidogenic peptide Abeta42 (Aβ-42), the peptide strongly associated with Alzheimer''s disease, recruited into condensates based on low complexity domains (LCDs) derived from the DEAD-box proteins Laf1, Dbp1 and Ddx4, which are associated with biological membraneless organelles. We show that interactions between Aβ-42 and the scaffold proteins promote sequestration and local increase of the peptide concentration within the condensates. Yet, heterotypic interactions within the condensates inhibit the formation of amyloid fibrils. These results demonstrate that biomolecular condensates could sequester aggregation-prone proteins and prevent aberrant aggregation events, despite the local increase in their concentration. Biomolecular condensates could therefore work not only as hot-spots of protein aggregation but also as protective reservoirs, since the heterogenous composition of the condensates could prevent the formation of ordered fibrillar aggregates.Biomolecular condensates sequester an aggregation-prone peptide and prevent its aggregation, showing that heterotypic interactions within the condensates can prevent the formation of amyloid fibrils, despite the local increase in concentration. 相似文献
2.
Three kinds of diffusion samplers, conceived to perform long-term samplings in indoor sites are illustrated in this work. Two of them, in part deriving from the previous "Analyst for VOC" device, extend the field of application up to the semi-volatile organic compounds (SVOC), PAHs and nicotine in particular. A third device, which employs a basic barium hydroxide solution as an absorbing medium, is proposed for the determination of carbon dioxide levels which indicate the air change quality in the indoor sites. Laboratory and field experiments, performed in order to assess the reliability of the proposed devices, are shown. A monthly monitoring campaign, performed at three private apartments in Rome and its outskirts highlights that the indoor pollution levels are a complex function of various concurrent and opposite factors, like external air pollution, internal sources, air change rate and sink effect of surfaces, which contribute to depletion phenomena through adsorption and/or decomposition processes. 相似文献
3.
Results obtained by using "Analyst", a long-term diffusive sampler, in some monitoring campaigns, performed for the determination of benzene and the volatile aromatic pollutants, in five cities of the Italian Umbria Region and at the city of Forlì, are presented and discussed. First results of an inter comparison between the "Analyst" and "radial-type" diffusive samplers, carried out by the Regional Agency for the Ambient Protection (ARPA) of Forlì, point out substantial advantages with the long-time sampling devices. 相似文献
4.
Several catalyzed alkylation reactions of 9-methyladenine by a model [CPI, cyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one (1)] of duocarmycin anticancer drugs have been compared to the uncatalyzed reaction in gas phase and in water solvent bulk, using density functional theory at the B3LYP level with the 6-31+G(d,p) basis set and C-PCM solvation model. The effect on the CPI reactivity induced by water, formic and phosphoric acids (general acid catalysis), H3O+ (specific acid catalysis), sodium, and ammonium cation complexation (cationic catalysis) has been investigated. The calculations indicate that the specific acid catalysis and the catalysis induced by sodium cation complexation are strong in the gas phase, but solvation reduces them dramatically by electrostatic effects. The specific acid catalysis is still operative, but strongly reduced in water solution, where the reaction barrier is reduced by 8.6 kcal mol(-1) in comparison to the uncatalyzed reaction. The general acid catalysis induced by phosphoric acid (-7.3 kcal mol(-1)) and the catalysis induced by Na+ and NH4+ complexation become competitive, with a catalytic effect of -3.6 and -4.1 kcal mol(-1) in water, respectively. With the specific acid catalysis, the high acidity (low pK(a) value) of the conjugated acid of CPI (CPIH+), computed in water solution using both C-PCM (pK(a) = +2.6) and PCM-B3LYP/6-31+G(d,p) (pK(a) = +2.4) solvation models, suggests that the catalytic effects induced by NH4+ complexation could become more important than the specific acid catalysis and the general catalysis by H3PO4 under physiological conditions, due to concentration effects of the catalysts. 相似文献
5.
Marchetti N Dondi F Felinger A Guerrini R Salvadori S Cavazzini A 《Journal of chromatography. A》2005,1079(1-2):162-172
The Reversed-phase (RP) gradient elution chromatography of nociceptin/orphanin FQ (N/OFQ), a neuropeptide with many biological effects, has been modeled under linear and non-linear conditions. In order to do this, the chromatographic behavior has been studied under both linear and nonliner conditions under isocratic mode at different mobile phase compositions--ranging from 16 to 19% (v/v) acetonitrile (ACN) in aqueous trifluoracetic acid (TFA) 0.1% (v/v)-on a C-8 column. Although the range of mobile phase compositions investigated was quite narrow, the retention factor of this relatively small polypeptide (N/OFQ is a heptadecapeptide) has been found to change by more than 400%. In these conditions, gradient operation resulted thus to be the optimum approach for non-linear elution. As the available amount of N/OFQ was extremely reduced (only a few milligrams), the adsorption isotherms of the peptide, at the different mobile phase compositions examined, have been measured through the so-called inverse method (IM) on a 5 cm long column. The adsorption data at different mobile phase compositions have been fitted to several models of adsorption. The dependence of the isotherm parameters on the mobile phase composition was modeled by using the linear solvent strength (LSS) model and a generalized Langmuir isotherm that includes the mobile phase composition dependence. The overloaded gradient separation of N/OFQ has been modeled by numerically solving the equilibrium-dispersive (ED) model of chromatography under a selected gradient elution mode, on the basis of the previously determined generalized Langmuir isotherm. The agreement between theoretical calculations and experimental overloaded band profiles appeared reasonably accurate. 相似文献
6.
The alkylation reaction of 9-methyladenine and 9-methylguanine (as prototype substrates of deoxy-adenosine and -guanosine), by the parent o-quinone methide (o-QM), has been investigated in the gas phase and in aqueous solution, using density functional theory at the B3LYP/6-311+G(d,p) level. The effect of the medium on the reactivity, and on the stability of the resulting adducts, has been investigated by using the C-PCM solvation model to assess which adduct arises from the kinetically favorable path, or from an equilibrating process. The calculations indicate that the most nucleophilic site of the methyl-substituted nucleobases in the gas phase is the guanine oxygen atom (O(6)) (DeltaG()(gas) = 5.6 kcal mol(-)(1)), followed by the adenine N1 (DeltaG)(gas) = 10.3 kcal mol(-)(1)), while other centers exhibit a substantially lower nucleophilicity. The bulk effect of water as a solvent is the dramatic reduction of the nucleophilicity of both 9-methyladenine N1 (DeltaG)(solv) = 14.5 kcal mol(-)(1)) and 9-methylguanine O(6) (DeltaG)(solv) = 17.0 kcal mol(-)(1)). As a result there is a reversal of the nucleophilicity order of the purine bases. While O(6) and N7 nucleophilic centers of 9-methylguanine compete almost on the same footing, the reactivity gap between N1 and N7 of 9-methyladenine in solution is highly reduced. Regarding product stability, calculations predict that only two of the adducts of o-QM with 9-methyladenine, those at NH(2) and N1 positions, are lower in energy than reactants, both in the gas phase and in water. However, the adduct at N1 can easily dissociate in water. The adducts arising from the covalent modification of 9-methylguanine are largely more stable than reactants in the gas phase, but their stability is markedly reduced in water. In particular, the oxygen alkylation adduct becomes slightly unstable in water (DeltaG(solv) = +1.4 kcal mol(-)(1)), and the N7 alkylation product remains only moderately more stable than free reactants (DeltaG(solv) = -2.8 kcal mol(-)(1)). Our data show that site alkylations at the adenine N1 and the guanine O(6) and N7 in water are the result of kinetically controlled processes and that the selective modification of the exo-amino groups of guanine N2 and adenine N6 are generated by thermodynamic equilibrations. The ability of o-QM to form several metastable adducts with purine nucleobases (at guanine N7 and O(2), and adenine N1) in water suggests that the above adducts may act as o-QM carriers. 相似文献
7.
We have used energy minimization calculations to study a number of conformations of uncomplexed valinomycin. In certain cases, x-ray diffraction atomic coordinates were used directly as input coordinates, while in other cases, conformations were found by altering the x-ray coordinates prior to minimization. Five calculated conformations are reported along with their relative energies. The conformation found theoretically to be the most stable is in agreement with earlier, cruder calculations, but does not correspond to the predominant conformation observed in nonpolar solvents. A possible rationale is presented. 相似文献
8.
Stefanie K. Fehler Gerald Pratsch Walter Huber Alain Gast Remo Hochstrasser Michael Hennig Markus R. Heinrich 《Tetrahedron letters》2012,53(17):2189-2194
3-Aryltyramines were prepared in one single step from tyramine and various arenediazonium salts by radical arylation. Binding as well as enzyme inhibition data of the 14 compounds do not prove true interaction with BACE-1. In contrast, with BACE-2 inhibition and binding could be confirmed indicating that 3-aryltyramines are potential starting points for a drug discovery effort. 相似文献
9.
10.
Terrettaz S Ulrich WP Guerrini R Verdini A Vogel H 《Angewandte Chemie (International ed. in English)》2001,40(9):1740-1743