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101.
Dr. Stefano Elli Dr. Eduardo Stancanelli Dr. Zhangjie Wang Dr. Maurice Petitou Prof. Jian Liu Dr. Marco Guerrini 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(51):11814-11818
Heparin binds to and activates antithrombin (AT) through a specific pentasaccharide sequence, in which a trisaccharide subsite, containing glucuronic acid (GlcA), has been considered as the initiator in the recognition of the polysaccharide by the protein. Recently it was suggested that sulfated iduronic acid (IdoA2S) could replace this “canonical” GlcA. Indeed, a heparin octasaccharidic sequence obtained by chemoenzymatic synthesis, in which GlcA is replaced with IdoA2S, has been found to similarly bind to and activate antithrombin. By using saturation-transfer-difference (STD) NMR, NOEs, transferred NOEs (tr-NOEs) NMR and molecular dynamics, we show that, upon binding to AT, this IdoA2S unit develops comparable interactions with AT as GlcA. Interestingly, two IdoA2S units, both present in a 1C4-2S0 equilibrium in the unbound saccharide, shift to full 2S0 and full 1C4 upon binding to antithrombin, providing the best illustration of the critical role of iduronic acid conformational flexibility in biological systems. 相似文献
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Mireia Casasampere Eduardo Izquierdo Josefina Casas Jos Luís Abad Xiao Liu Ruijuan Xu Cungui Mao Young-Tae Chang Antonio Delgado Gemma Fabrias 《Chemical science》2020,11(48):13044
The use of intact cells in medical research offers a number of advantages over employing cell-free systems. In diagnostics, cells isolated from liquid biopsies can be directly used, speeding up the time of analysis and diminishing the risk of protein degradation by sample manipulation. In drug discovery, studies in live cells take into account aspects neglected in cell-free systems, such as uptake, metabolization, and subcellular concentration by compartmentalization of potential drug candidates. Therefore, probes for studies in cellulo are of paramount importance. Acid ceramidase (AC) is a lysosomal enzyme that hydrolyses ceramides into sphingoid bases and fatty acids. The essential role of this enzyme in the outburst and progress of several diseases, some of them still incurable, is well sustained. Despite the great clinical relevance of AC as a biomarker and therapeutic target, the specific monitoring of AC activity in live cells has remained elusive due to the concomitant existence of neutral and alkaline ceramidases. In this work, we report that 1-deoxydihydroceramides are exclusively hydrolysed by AC. Using N-octanoyl-18-azidodeoxysphinganine as a probe and a BODIPY-substituted bicyclononyne, we show the click-reliant predominant staining of lysosomes, with extra-lysosomal labeling also occurring in some cells. Importantly, using pharmacological and genetic tools together with high resolution mass spectrometry, we demonstrate that both lysosomal and extra-lysosomal staining are AC-dependent. These findings are translated into the specific flow cytometry monitoring of AC activity in intact cells, which fills an important gap in the field of diseases linked to altered AC activity.The use of intact cells in medical research offers a number of advantages over employing cell-free systems. 相似文献
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Determination of mazindol in human oral fluid by high performance liquid chromatography–electrospray ionization mass spectrometry 下载免费PDF全文
Marcella Herbstrith de Oliveira Graciela Carlos Ana Maria Bergold Flavio Pechansky Renata Pereira Limberger Pedro Eduardo Fröehlich 《Biomedical chromatography : BMC》2014,28(8):1064-1069
Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography–mass spectrometry (LC‐MS). The LC system consisted of an LC‐MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2–20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Cláudia A. Kodaira Ana Valéria S. Lourenço Maria Cláudia F.C. Felinto Eduardo M.R. Sanchez Francisco J.O. Rios Luiz Antonio O. Nunes Magnus Gidlund Oscar L. Malta Hermi F. Brito 《Journal of luminescence》2011,131(4):727-731
Neodymium based fluorescence presents several advantages in comparison to conventional rare earth or enzyme-substrate based fluorescence emitting sources (e.g.Tb, HRP) . Based on this fact we have herein explored a Nd-based fluoroimmunoassay. We efficiently detected the presence of an oxidized low-density lipoprotein (oxLDL) in human plasma a well-known marker for cardiovascular diseases, which causes around 30% of deaths worldwide. Conventional fluoroimmunoassay uses time-resolved luminescence techniques, with detection in the visible range, to eliminate the fluorescence background from the biological specimens. By using an immunoassay based on functionalized Y2O3:Nd3+ nanoparticles, where the excitation and emission processes in the Nd3+ ion occur in the near-infrared (NIR) region, we have succeeded in eliminating the interferences from the biological fluorescence background, avoiding the use of time-resolved techniques. This yields higher emission intensity from the Nd3+-nanolabels and efficient detection of anti-oxidized low-density lipoproteins (anti-oxLDL) by Y2O3:Nd3+-antibody-antigen conjugation, leading to a novel biolabeling method. 相似文献
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