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81.
Gitto R Damiano FM De Luca L Ferro S Vullo D Supuran CT Chimirri A 《Bioorganic & medicinal chemistry》2011,19(23):7003-7007
In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition. 相似文献
82.
Milite C Castellano S Benedetti R Tosco A Ciliberti C Vicidomini C Boully L Franci G Altucci L Mai A Sbardella G 《Bioorganic & medicinal chemistry》2011,19(12):3690-3701
A novel class of KAT modulators (long chain alkylidenemalonates, LoCAMs) has been identified. Variations of the alkyl chain length can change the activity profile from inhibition of both KAT3A/KAT2B (as derivative 2a) to the peculiar profile of pentadecylidenemalonate 1b, the first activator/inhibitor of histone acetyltransferases. Together with the powerful apoptotic effect (particularly notable if considering that anacardic acid and other KAT inhibitors are not cell permeable) appoint them as valuable biological tools to understand the mechanisms of lysine acetyltransferases. 相似文献
83.
This minireview deals of a protein, a class III secreted peroxidase, present as unique isoform in the latex of the perennial
Mediterranean shrub Euphorbia
characias. The paper reports on the molecular properties, on the structures (primary, secondary and tertiary), and on the catalytic
mechanism of this enzyme. Here is also reported the extraordinary effect of calcium ions on the structure and on the enzyme
activity of Euphorbia peroxidase. These ions can either enhance the catalytic efficiency of the enzyme toward some substrates or can regulate the
ability of the enzyme to execute different metabolic pathways toward the same substrate. This review will give a valuable
reference to the peroxidase fans and the general readers will find many thorough suggestions for future researches giving
birth to new studies and important discoveries. 相似文献
84.
Gómez-Barrena E Rosset P Müller I Giordano R Bunu C Layrolle P Konttinen YT Luyten FP 《Journal of cellular and molecular medicine》2011,15(6):1266-1286
Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. 相似文献
85.
86.
Esposito G Scuderi C Valenza M Togna GI Latina V De Filippis D Cipriano M Carratù MR Iuvone T Steardo L 《PloS one》2011,6(12):e28668
Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to be involved in the etiology of pathological features of Alzheimer's disease (AD). Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has attracted much attention because of its promising neuroprotective properties in rat AD models, even though the mechanism responsible for such actions remains unknown. This study was aimed at exploring whether CBD effects could be subordinate to its activity at PPARγ, which has been recently indicated as its putative binding site. CBD actions on β-amyloid-induced neurotoxicity in rat AD models, either in presence or absence of PPAR antagonists were investigated. Results showed that the blockade of PPARγ was able to significantly blunt CBD effects on reactive gliosis and subsequently on neuronal damage. Moreover, due to its interaction at PPARγ, CBD was observed to stimulate hippocampal neurogenesis. All these findings report the inescapable role of this receptor in mediating CBD actions, here reported. 相似文献
87.
Phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2] is a key regulator of endocytosis. PtdIns(4,5)P2 generation at the plasma membrane in yeast is mediated by the kinase Mss4p, but the mechanism underlying the temporal and spatial activation of Mss4p to increase formation of PtdIns(4,5)P2 at appropriate sites is not known. Here, we show that ADP ribosylation factor (Arf)3p, the yeast homologue of mammalian Arf6, is necessary for wild-type levels of PtdIns(4,5)P2 at the plasma membrane. Arf3p localizes to dynamic spots at the membrane, and the behaviour of these is consistent with it functioning in concert with endocytic machinery. Localization of Arf3p is disrupted by deletion of genes encoding an ArfGAP homology protein Gts1p and a guanine nucleotide exchange factor Yel1p. Significantly, deletion of arf3 causes a reduction in PtdIns(4,5)P2 at the plasma membrane, while increased levels of active Arf3p, caused by deletion of the GTPase-activating protein Gts1, increase PtdIns(4,5)P2 levels. Furthermore, elevated Arf3p correlates with an increase in the number of endocytic sites. Our data provide evidence for a mechanism in yeast to positively regulate plasma membrane production of PtdIns(4,5)P2 levels and that these changes impact on endocytosis. 相似文献
88.
BFRF1 of Epstein-Barr virus is essential for efficient primary viral envelopment and egress 下载免费PDF全文
Farina A Feederle R Raffa S Gonnella R Santarelli R Frati L Angeloni A Torrisi MR Faggioni A Delecluse HJ 《Journal of virology》2005,79(6):3703-3712
The molecular mechanisms that underlie maturation and egress of Epstein-Barr virus (EBV) virions are only partially characterized. We have recently shown that the BFRF1 gene, the EBV positional homolog of herpes simplex virus type 1 and pseudorabies virus UL34, is expressed early during EBV lytic replication and that it is found predominantly on the nuclear membrane (A. Farina, R. Santarelli, R. Gonnella, R. Bei, R. Muraro, G. Cardinali, S. Uccini, G. Ragona, L. Frati, A. Faggioni, and A. Angeloni, J. Virol. 74:3235-3244, 2000). These data suggest that the BFRF1 protein might be involved in viral primary envelopment. To precisely determine the function of this protein, we have constructed an EBV mutant devoid of the BFRF1 gene (BFRF1-KO). 293 cells carrying BFRF1-KO showed no differences in comparison with wild-type EBV in terms of DNA lytic replication or expression of late viral proteins upon induction of the lytic cycle. However, binding assays and infection experiments using cell lines or human cord blood lymphocytes showed a clear reduction in the viral mutant titers. Complementation experiments with BFRF1-KO and a BFRF1 expression vector restored viral titers to levels similar to those for the wild-type control, showing that the modifications that we introduced were limited to the BFRF1 gene. Electron microscopic observations showed that the reduction in viral titers was due to sequestration of EBV nucleocapsids in the nuclei of lytically induced cells. This suggests that BFRF1 is involved in transport of the maturing virion across the nuclear membrane. This hypothesis was further supported by the observation that BFRF1 is present in maturing intracellular virions but not in their extracellular counterparts. This implies that BFRF1 is a key protein for EBV maturation. 相似文献
89.
Copper/quinone amine oxidases contain Cu(II) and the quinone of 2,4,5-trihydroxyphenylalanine (topaquinone; TPQ) as cofactors. TPQ is derived by post-translational modification of a conserved tyrosine residue in the protein chain. Major advances have been made during the last decade toward understanding the structure/function relationships of the active site in Cu/TPQ amine oxidases using specific inhibitors. Mechanism-based inactivators are substrate analogues that bind to the active site of an enzyme being accepted and processed by the normal catalytic mechanism of the enzyme. During the reaction a covalent modification of the enzyme occurs leading to irreversible inactivation. In this review mechanism-based inactivators of plant Cu/TPQ amine oxidases from the pulses lentil (Lens esculenta), pea (Pisum sativum), grass pea (Lathyrus sativus) and sainfoin (Onobrychis viciifolia,) are described. Substrates forming, in aerobiotic and in anaerobiotic conditions, killer products that covalently bound to the quinone cofactor or to a specific amino acid residue of the target enzyme are all reviewed. 相似文献
90.
Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease 总被引:7,自引:0,他引:7
Iacobellis G Pistilli D Gucciardo M Leonetti F Miraldi F Brancaccio G Gallo P di Gioia CR 《Cytokine》2005,29(6):251-255
BACKGROUND: Intra-peritoneal adipose tissue is recognized as a predictor of metabolic syndrome and may contribute to the risk for cardiovascular disease by the production of adipocytokines, including adiponectin. Nevertheless, there is no knowledge on whether other visceral depots of adipose tissue, including the epicardial fat, have any metabolically active role, including production of adiponectin. AIM OF THE STUDY: We sought to evaluate adiponectin protein expression in epicardial adipose tissue in vivo both in patients with severe coronary artery disease (CAD) and in subjects without CAD. METHODS: Twenty-two patients were enrolled for the study. We selected 16 patients who underwent elective coronary artery bypass graft surgery for critical CAD, 5 who underwent surgery for valve replacement and 1 for correction of an interatrial defect. Epicardial adipose tissue biopsy samples were obtained before the initiation of cardiopulmonary bypass. Adiponectin protein level in epicardial adipose tissue was evaluated by Western blotting. RESULTS: Adiponectin protein value, expressed as adiponectin/actin ratio, in epicardial adipose tissue was significantly lower in patients with severe CAD than in those without CAD (1.42 +/- 0.77 vs 2.36 +/- 0.84 p = 0.02, 95% CI 0.64-1.74). CONCLUSIONS: This study showed for the first time that human epicardial adipose tissue expresses adiponectin. Adiponectin expression is significantly lower in epicardial fat isolated from patients with CAD. 相似文献