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31.
Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors
Eva Shannon Schiffrer Matic Proj Martina Gobec Luka Rejc Andrej terman Janez Mravljak Stanislav Gobec Izidor Sosi
《Molecules (Basel, Switzerland)》2021,26(2)
The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases. However, the development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. We previously reported 7H-furo[3,2-g]chromen-7-one (psoralen)-based compounds with an oxathiazolone warhead as selective inhibitors of the chymotrypsin-like (β5i) subunit of immunoproteasome. Here, we describe the influence of the electrophilic warhead variations at position 3 of the psoralen core on the inhibitory potencies. Despite mapping the chemical space with different warheads, all compounds showed decreased inhibition of the β5i subunit of immunoproteasome in comparison to the parent oxathiazolone-based compound. Although suboptimal, these results provide crucial information about structure–activity relationships that will serve as guidance for the further design of (immuno)proteasome inhibitors. 相似文献
32.
A. D. Pogrebnjak A. A. Dem’yanenko V. M. Beresnev O. V. Sobol’ O. M. Ivasishin K. Oyoshi Y. Takeda H. Amekura A. I. Kupchishin 《Physics of the Solid State》2016,58(7):1453-1457
The recrystallization of the structure of an X-ray amorphous AlN–TiB2–TiSi2 coating containing short-range order regions with characteristic sizes of 0.8–1.0 nm has been performed using a negative gold ion (Au–) beam and high-temperature annealing. Direct measurements using methods of high-resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray spectral (EDXS) microanalysis have demonstrated that thermal annealing at a temperature of 1300°C in air results in the formation of nanoscale (10–15 nm) phases AlN, AlB2, Al3O3, and TiO2, whereas the ion implantation of negative ions Au– leads to a fragmentation (decrease in the size) of nanograins to 2–5 nm with the formation of spheroidal gold nanocrystallites a few nanometers in size, as well as to the formation of an amorphous oxide film in the depth (near-surface layer) of the coating due to ballistic ion mixing and collision cascades. 相似文献
33.
Anna Kopcakova Zuzana Stramova Simona Kvasnova Andrej Godany Zuzana Perhacova Peter Pristas 《Chemical Papers》2014,68(11):1435-1442
The ability of MALDI TOF MS (matrix-assisted laser desorption ionisation time-of-flight mass spectrometry) to identify cultivable microflora from two waste disposal sites from non-ferrous metal industry was analysed. Despite the harsh conditions (extreme pH values and heavy metal content in red mud disposal site from aluminium production or high heavy metal content in nickel sludge), relatively high numbers of bacteria were recovered. In both environments, the bacterial community was dominated by Gram-positive bacteria, especially by actinobacteria. High-quality MALDI TOF mass spectra were obtained but most of the bacteria isolates could be not identified using MALDI Biotyper software. The overall identification rate was lower than 20 %; in two of the environments tested identification rates were lower than 10 %. As a dominant bacterial species, Microbacterium spp. in drainage water from an aluminium red mud disposal site near ?iar nad Hronom, Bacillus spp. in red mud samples from the same site, and Arthrobacter spp. from nickel smelter sludge near Sereï were identified by a combination of the Biolog system and 16S rRNA sequence analysis. As the primary focus of the MALDI TOF MS-based methodology is directed towards medically important bacteria, reference database spectra expansion and refinement are needed to improve the ability of MALDI TOF MS to identify environmental bacteria, especially those from extreme environments. 相似文献
34.
A wavelet decomposition of (nonpolynomial) third height splines of Hermitian type is obtained. Decomposition and reconstruction
formulas are constructed in the case of an additional grid point. It is shown that the basis wavelets are three times continuously
differentiable and are compactly supported. Bibliography: 12 titles. 相似文献
35.
Gorazd Hribar Andrej Žnidaršič Marjan Bele Uroš Maver Simon Caserman Miran Gaberšček Vladka Gaberc-Porekar 《Journal of nanoparticle research》2011,13(7):3019-3032
The authors’ intention was to prepare nanometer-sized zinc-phosphate nanoparticles that would be capable of binding histidine-rich
TNF-α analogs onto their surface via a coordinative bond. Zinc-phosphate nanoparticles with a size of around 60 nm were prepared
by a wet precipitation method and characterized using SEM, EDX, XRD, and DLS. First, BSA was bound as a testing protein, afterward
two TNF-α analogs with decreased activity were bound to the described nanoparticles. The efficiency of binding and the existence
of coordinative bond were confirmed with SDS-PAGE analysis. During binding, particle storage, and release experiments, the
prepared TNF-α analogs retained their biological activity—hence the epitopes necessary for formation of antibodies stayed
intact. The particle size did not change within a period of 2 weeks. No significant agglomeration was observed, the particles
could be quickly dispersed in ultrasound. The present nanoparticles and the general approach of coordinative binding are widely
applicable for natural and engineered histidine-rich proteins. The nanoparticles bearing appropriate TNF-α analogs could also
be potentially used for active immunotherapy to tackle the chronic inflammatory diseases associated with pathogenically elevated
levels of TNF-α. 相似文献
36.
In this paper, we present several methods for the construction of elliptic curves with large torsion group and positive rank over number fields of small degree. We also discuss potential applications of such curves in the elliptic curve factorization method (ECM). 相似文献
37.
Martínez-Sanchis Daniel Sternin Andrej Tagscherer Kenneth Sternin Daniel Haidn Oskar Tajmar Martin 《Flow, Turbulence and Combustion》2022,109(3):813-838
Flow, Turbulence and Combustion - Direct numerical simulations of a turbulent premixed stoichiometric methane-oxygen flame were conducted. The chosen combustion pressure was 20 bar, to... 相似文献
38.
Terech P Sangeetha NM Demé B Maitra U 《The journal of physical chemistry. B》2005,109(25):12270-12276
Aqueous gels derived from three cationic 24-nor 3,12-dihydroxy cholane (DC) derivatives with N-methyl-2-pyrrolidinone (NMP), N-methylmorpholine (NMM), and 1,4-diazabicyclo[2.2.2]octane (DABCO) at the side chain positions have been exhaustively characterized by small-angle neutron-scattering experiments. Although the molecular structures differ slightly by the heterocycle grafted to the steroid core, the derived gels exhibit a range of structural behaviors at the nanoscale that depart from those observed with simple deoxycholate systems. The NMM-DC aggregates are ribbons with a bimolecular thickness of t = 37 A and an anisotropy of the section b/a approximately 0.1. DABCO-DC exhibits a remarkable transition from ribbons (t = 29.5 A, b/a = 0.18) to thicker cylindrical fibers (R approximately 59 A), involving four original ribbons, upon a concentration increase. The NMP-DC system forms thick cylindrical fibers (R approximately 68 A) with steroid molecules organized in a specific morphology. Bilayered or interdigited structures are formed and favored by the presence of multiple polar interaction centers in the DC molecules. Secondary aggregation mechanisms are invoked in the formation of bundles having a lower cross-sectional anisotropic symmetry and exhibiting Bragg peaks corresponding to molecular length periodicities. The relations between the structural information and the rheological properties are discussed. 相似文献
39.
40.
The Kováts retention indices of all 93 acyclic octenes on polydimethylsiloxane and squalane as stationary phases as well as their mass spectra were measured. The means of gas chromatography-mass spectrometry (GC-MS) were used for confirmation of GC identification as well as for mass spectrometric deconvolution of the majority of gas chromatographic unseparated isomeric octene peaks. The distinction between corresponding E and Z acyclic octenes, that is either difficult or even impossible by means of GC-MS, was obtained on the basis of larger temperature coefficients of retention indices for Z isomeric octenes than for corresponding E isomers. The retention data expressed as homomorphy factors were correlated with the degree of branching, position of double bond, and position of alkyl group with respect to the double bond of acyclic octenes, and the structure-retention relationships were formulated. The 81 acyclic octenes were identified in FCC gasoline. 相似文献