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131.
132.
Anton Shetnev Roman Shlenev Julia Efimova Sergey Ivanovskii Alexey Tarasov Anél Petzer Jacobus P. Petzer 《Bioorganic & medicinal chemistry letters》2019,29(21):126677
The present study investigates the monoamine oxidase (MAO) inhibition properties of a series of ten 5-aryl-1,3,4-oxadiazol-2-ylbenzenesulfonamides. The target compounds were synthesized by dehydration of the corresponding N,N′-diacylhydrazines with phosphorus oxychloride to yield the 1,3,4-oxadiazole cycle with concomitant transformation of the sulfonamide to the sulfonyl chloride group. Treatment with aqueous ammonia in acetonitrile regenerated the target sulfonamides. The results of the enzymology document that these compounds are potent and specific MAO-B inhibitors with the most potent compound exhibiting an IC50 value of 0.0027 µM. An analysis of the structure-activity relationships shows that the 4-benzenesulfonamides are significantly more potent MAO-B inhibitors than the corresponding 3-benzenesulfonamides, and that the corresponding N,N′-diacylhydrazine synthetic precursors are weak MAO inhibitors. Although MAO inhibition by oxadiazole compounds are known, this is the first report of nanomolar MAO inhibition potencies recorded for sulfonamide derivatives. MAO-B specific inhibitors such as those discovered here may be of interest in the treatment of neurodegenerative disorders such as Parkinson’s disease. 相似文献
133.
In several experimental techniques D2O rather then H2O is often used as a solvent for proteins. Concerning the influence of the solvent on the stability of the proteins, contradicting results have been reported in literature. In this paper the influence of H2O-D2O solvent substitution on the stability of globular protein structure is determined in a systematic way. The differential scanning calorimetry technique is applied to allow for a thermodynamic analysis of two types of globular proteins: hen's egg lysozyme (LSZ) with relatively strong internal cohesion ("hard" globular protein) and bovine serum albumin (BSA), which is known for its conformational adaptability ("soft" globular protein). Both proteins tend to be more stable in D2O compared to H2O. We explain the increase of protein stability in D2O by the observation that D2O is a poorer solvent for nonpolar amino acids than H2O, implying that the hydrophobic effect is larger in D2O. In case of BSA the transitions between different isomeric forms, at low pH values the Nm and F forms, and at higher pH values Nm and B, were observed by the presence of a supplementary peak in the DSC thermogram. It appears that the pH-range for which the Nm form is the preferred one is wider in D2O than in H2O. 相似文献
134.
135.
Manuel Balparda Marlene Elssser Mariana B. Badia Jonas Giese Anastasiia Bovdilova Meike Hüdig Lisa Reinmuth Jürgen Eirich Markus Schwarzlnder Iris Finkemeier Mareike Schallenberg-Rüdinger Veronica G. Maurino 《The Plant journal : for cell and molecular biology》2022,109(1):92-111
Plants need to rapidly and flexibly adjust their metabolism to changes of their immediate environment. Since this necessity results from the sessile lifestyle of land plants, key mechanisms for orchestrating central metabolic acclimation are likely to have evolved early. Here, we explore the role of lysine acetylation as a post-translational modification to directly modulate metabolic function. We generated a lysine acetylome of the moss Physcomitrium patens and identified 638 lysine acetylation sites, mostly found in mitochondrial and plastidial proteins. A comparison with available angiosperm data pinpointed lysine acetylation as a conserved regulatory strategy in land plants. Focusing on mitochondrial central metabolism, we functionally analyzed acetylation of mitochondrial malate dehydrogenase (mMDH), which acts as a hub of plant metabolic flexibility. In P. patens mMDH1, we detected a single acetylated lysine located next to one of the four acetylation sites detected in Arabidopsis thaliana mMDH1. We assessed the kinetic behavior of recombinant A. thaliana and P. patens mMDH1 with site-specifically incorporated acetyl-lysines. Acetylation of A. thaliana mMDH1 at K169, K170, and K334 decreases its oxaloacetate reduction activity, while acetylation of P. patens mMDH1 at K172 increases this activity. We found modulation of the malate oxidation activity only in A. thaliana mMDH1, where acetylation of K334 strongly activated it. Comparative homology modeling of MDH proteins revealed that evolutionarily conserved lysines serve as hotspots of acetylation. Our combined analyses indicate lysine acetylation as a common strategy to fine-tune the activity of central metabolic enzymes with likely impact on plant acclimation capacity. 相似文献
136.
Boiko Dmytro I. Shkodina Anastasiia D. Hasan Mohammad Mehedi Bardhan Mainak Kazmi Syeda Kanza Chopra Hitesh Bhutra Prerna Baig Atif Amin Skrypnikov Andrii M. 《Neurochemical research》2022,47(10):2909-2924
Neurochemical Research - A complex pathogenesis involving several physiological systems is theorized to underline the development of depressive disorders. Depression is accompanied by circadian... 相似文献
137.
Emotional evaluations of short fragments of classical music were compared in students (boys and girls) in the state of relative rest and during examinations. Substantial gender differences were found with respect to the sign and intensity of the emotional evaluations. The functional states of subjects affect the numbers of positive, neutral, and negative evaluations of musical fragments. 相似文献
138.
Mikhail V. Kovalchuk Anastasiia S. Boikova Yulia A. Dyakova Kseniia B. Ilina Petr V. Konarev Alyona E. Kryukova 《Journal of biomolecular structure & dynamics》2019,37(12):3058-3064
Communicated by Ramaswamy H. Sarma 相似文献
139.
Several ClchR clones of CHO-K1 have been isolated by a single- and multistep selection. They are distinct from each other both in the level of colchicine resistance and in the phenotypic stability of this feature. Fluctuation tests showed that the generation of drug resistant variants in the wild type population was random and did not depend on the action of selective agent. The rate of spontaneous occurrence of these variants was approximatley 1.79 x 10(-6) per cell per generation. Treatment with MNNG enhanced the frequency of ClchR variants by 100 fold. Cytotoxic effect of Clch on resistant cells has been potentiated by non-ionic detergent Tween 80. All the stable resistant clones appeared to be cross resistant to unrelated drugs such as actinomycin D, ethydium bromide and aminopterine . These two observations allow to suggest the alteration of membrane permeability as a mechanism of resistance to Clch . Genetical mechanisms of Clch -resistance of cells are discussed. 相似文献
140.
N D Gabriélian N V Prokazova A V Komleva L N Kashnikova I V Efimova A F Panasiuk 《Biokhimii?a (Moscow, Russia)》1990,55(8):1402-1407
A comparative study of phospho- and glycosphingolipids of cultured skin fibroblast from healthy donors and from patients with systemic sclerodermia (SSD) was carried out. It was shown that the total phospholipid content in SSD fibroblasts is elevated. No significant changes in the concentration of neutral glycosphingolipids were observed. The ganglioside composition of SSD cell cultures differs significantly from that of healthy donor cells. The concentration of the gangliosides, GM3 and GM1, is decreased; no ganglioside GD1a was found in SSD fibroblasts. The data obtained are suggestive of changes in the properties of fibroblast surface which can be manifested both in the impaired reception of matrix proteins and in the impairment of basic properties of the membrane. These changes are well correlated with the results of previous studies on the AMP cyclase system. 相似文献