153207-76-2Relevant articles and documents
ATP13A3 is a major component of the enigmatic mammalian polyamine transport system
Hamouda, Norin Nabil,van den Haute, Chris,Vanhoutte, Roeland,Sannerud, Ragna,Azfar, Mujahid,Mayer, Rupert,Calabuig, álvaro Cortés,Swinnen, Johannes V.,Agostinis, Patrizia,Baekelandt, Veerle,Annaert, Wim,Impens, Francis,Verhelst, Steven H.L.,Eggermont, Jan,Martin, Shaun,Vangheluwe, Peter
, (2021)
Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in WT cells induced a CHO-MG phenotype demonstrated as a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3, which has been previously genetically linked with pulmonary arterial hypertension, as a major component of the mammalian polyamine transport system that confers sensitivity to MGBG.
Catalytic "click" rotaxanes: A substoichiometric metal-template pathway to mechanically interlocked architectures
Aucagne, Vincent,Haenni, Kevin D.,Leigh, David A.,Lusby, Paul J.,Walker, D. Barney
, p. 2186 - 2187 (2006)
A route to mechanically interlocked architectures that requires only a catalytic quantity of template is described. The strategy utilizes the Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes. Chelating the Cu(I) to an endotopic-binding macrocycle means that the metal atom binds to the alkyne and azide in such a way that the metal-mediated bond-forming reaction occurs through the cavity of the macrocycle, forming a rotaxane. Addition of pyridine to the reaction mixture enables the Cu(I) to turn over during the reaction, permitting substoichiometric amounts of the metal to be used. The yields are very high for a rotaxane-forming reaction (up to 94% with stoichiometric Cu(I); 82% with 20 mol % of Cu(I)), and the procedure is practically simple to do (no requirement for an inert atmosphere nor dried or distilled solvents). Copyright
Biotin-decorated NIR-absorbing nanosheets for targeted photodynamic cancer therapy
Perumal, Devanathan,Golla, Murali,Pillai, Kavya S.,Raj, Gowtham,Krishna P. K., Anusree,Varghese, Reji
supporting information, p. 2804 - 2810 (2021/04/07)
Targeted photodynamic therapy (PDT) is one of the promising approaches for the selective killing of cancerous cells without affecting the normal cells, and hence designing new strategies for targeted PDT is extremely important. Herein we report the design and synthesis of a new class of nanosheets derived from the self-assembly of the iodo-BODIPY-biotin conjugate as a photosensitizer for targeted PDT applications. The nanosheet exhibits a high extinction coefficient in the NIR region, high singlet oxygen efficiency, no toxicity in the dark and cell targeting ligands (biotin) on the surface, which are necessary features required for an ideal photosensitizer. Overexpression of sodium-dependent multivitamin transporters (SMVTs) in HeLa and A549 (biotin receptor positive cell lines) is explored for the selective uptake of the nanophotosensitizer through receptor mediated endocytosis (interaction between biotin and SMVT). Control experiments using a biotin receptor negative cell line (WI-38) are also carried out to confirm that the specific interaction between the SMVTs and biotin is mainly responsible for the selective uptake of the photosensitizer. Efficient killing of cancerous cells is demonstrated upon light irradiation through the generation of singlet oxygen and other reactive oxygen species around the cellular environment.
High-Yielding Water-Soluble Asymmetric Cyanine Dyes for Labeling Applications
Wolf, Natalia,Kersting, Louise,Herok, Christoph,Mihm, Cornelius,Seibel, Juergen
supporting information, p. 9751 - 9760 (2020/09/03)
A simple and efficient microwave-assisted synthesis of asymmetric pentamethine cyanine dyes with various functional groups was developed, which allows high-yielding results. The synthesized dyes are modifiable and suitable for single-molecule imaging in biological and medical sciences by application of click chemistry or classic esterification and amidation.
Visualization and quantification of cellular RNA production and degradation using a combined fluorescence and mass spectrometry characterization assay
Gao, Xiaoying,Shu, Xiao,Song, Yinuo,Cao, Jie,Gao, Minsong,Wang, Fengqin,Wang, Yizhen,Sun, Jing Zhi,Liu, Jianzhao,Tang, Ben Zhong
supporting information, p. 8321 - 8324 (2019/07/17)
Here we report a combined fluorescence and mass spectrometry assay which is capable of stably visualizing and quantifying cellular nucleoside-labeled RNA production and degradation. The fluorescence and mass spectrometry signals from cellular labeled RNAs
Design and Synthesis of Quenched Activity-based Probes for Diacylglycerol Lipase and α,β-Hydrolase Domain Containing Protein 6
van Rooden,Kohsiek,Kreekel,van Esbroeck,van den Nieuwendijk,Janssen,van den Berg,Overkleeft,van der Stelt
, p. 3491 - 3500 (2018/11/25)
Diacylglycerol lipases (DAGL) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. The fluorescent activity-based probes DH379 and HT-01 have been previously shown to label DAGLs and to cross-react with the serine hydrolase ABHD6. Here, we report the synthesis and characterization of two new quenched activity-based probes 1 and 2, the design of which was based on the structures of DH379 and HT-01, respectively. Probe 1 contains a BODIPY-FL and a 2,4-dinitroaniline moiety as a fluorophore–quencher pair, whereas probe 2 employs a Cy5-fluorophore and a cAB40-quencher. The fluorescence of both probes was quenched with relative quantum yields of 0.34 and 0.0081, respectively. The probes showed target inhibition as characterized in activity-based protein profiling assays using human cell- and mouse brain lysates, but were unfortunately not active in living cells, presumably due to limited cell permeability.
Fast and reliable generation of [18F]triflyl fluoride, a gaseous [18F]fluoride source
Pees,Sewing,Vosjan,Tadino,Herscheid,Windhorst,Vugts
supporting information, p. 10179 - 10182 (2018/09/13)
A novel strategy for the production of reactive [18F]fluoride has been developed, omitting time consuming azeotropic drying procedures. Gaseous [18F]triflyl fluoride is formed instantaneously at room temperature from hydrated [18F]fluoride, followed by distillation in less than 5 minutes into a dry aprotic solvent, in which dry [18F]fluoride is released in presence of base with >90% radiochemical yield. The reactivity of the [18F]fluoride has been confirmed by reaction with several model compounds and by the synthesis of the PET tracers [18F]fluoroestradiol ([18F]FES) and O-2-[18F]fluoroethyl-l-tyrosine ([18F]FET), providing good isolated radiochemical yields and molar activities of up to 123 GBq μmol?1.
High-Affinity “Click” RGD Peptidomimetics as Radiolabeled Probes for Imaging αvβ3 Integrin
Piras, Monica,Testa, Andrea,Fleming, Ian N.,Dall'Angelo, Sergio,Andriu, Alexandra,Menta, Sergio,Mori, Mattia,Brown, Gavin D.,Forster, Duncan,Williams, Kaye J.,Zanda, Matteo
supporting information, p. 1142 - 1151 (2017/07/25)
Nonpeptidic Arg-Gly-Asp (RGD)-mimic ligands were designed and synthesized by click chemistry between an arginine–azide mimic and an aspartic acid–alkyne mimic. Some of these molecules combine excellent in vitro properties (high αvβ3 affinity, selectivity, drug-like logD, high metabolic stability) with a variety of radiolabeling options (e.g., tritium and fluorine-18, plus compatibility with radio-iodination), not requiring the use of chelators or prosthetic groups. The binding mode of the resulting triazole RGD mimics to αvβ3 or αIIbβ3 receptors was investigated by molecular modeling simulations. Lead compound 12 was successfully radiofluorinated and used for in vivo positron emission tomography/computed tomography (PET/CT) studies in U87 tumor models, which showed only modest tumor uptake and retention, owing to rapid excretion. These results demonstrate that the novel click RGD mimics are excellent radiolabeled probes for in vitro and cell-based studies on αvβ3 integrin, whereas further optimization of their pharmacokinetic and dynamic profiles is necessary for successful use in in vivo imaging.
NOVEL SOLANIDINE-DERIVED COMPOUNDS
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Paragraph 0250-0260, (2016/06/28)
Novel solanidine-derived compounds, the synthesis method thereof and the uses of same in the fields of phytosanitary protection and health. In particular, the novel compounds have toxic and/or repellent properties in relation to aphids, as well as other properties.
Discovery of the First Environment-Sensitive Near-Infrared (NIR) Fluorogenic Ligand for α1-Adrenergic Receptors Imaging in Vivo
Ma, Zhao,Lin, Yuxing,Cheng, Yanna,Wu, Wenxiao,Cai, Rong,Chen, Shouzhen,Shi, Benkang,Han, Bo,Shi, Xiaodong,Zhou, Yubin,Du, Lupei,Li, Minyong
, p. 2151 - 2162 (2016/03/25)
Fluorescent ligands are gaining popularity as tools to aid GPCR research. Nonetheless, in vivo application of such tools is hampered due to their short excitation wavelengths in the visible range and lack of fluorogenic switch. Here we report the discovery of fluorescent ligands (3a-f) for α1-adrenergic receptors (α1-ARs) by conjugating the environment-sensitive fluorophore cyane 5 (Cy5) with the quinazoline pharmacophore. Among them, the conjugated compound 3a, with acylated piperazine and the shortest carbon chain spacer, exhibited potent binding and remarkable changes in fluorescence (10-fold) upon binding to α1-AR. Furthermore, it could be employed to selectively and specifically label α1-ARs with no washing procedures in single cells, prostate tissue slices, intact tumor xenografts and organs in living mice. Especially, the slice imaging results gave direct and visual evidence that there is a close relationship between α1-ARs and pathological prostate. It is anticipated that our fluorescent tools will find broad applications in the study of α1-AR pharmacology and physiology to aid development of novel therapeutics.
