62796-29-6Relevant articles and documents
Poly-(amidoamine) dendrimers with a precisely core positioned sulforhodamine B molecule for comparative biological tracing and profiling
Wu, Lin-Ping,Ficker, Mario,Mejls?e, S?ren L.,Hall, Arnaldur,Paolucci, Valentina,Christensen, J?rn B.,Trohopoulos, Panagiotis N.,Moghimi, Seyed M.
, p. 88 - 97 (2017)
We report on a simple robust procedure for synthesis of generation-4 poly-(amidoamine) (PAMAM) dendrimers with a precisely core positioned single sulforhodamine B molecule. The labelled dendrimers exhibited high fluorescent quantum yields where the absorbance and fluorescence spectrum of the fluorophore was not affected by pH and temperature. Since the stoichiometry of the fluorophore to the dendrimer is 1:1, we were able to directly compare uptake kinetics, the mode of uptake, trafficking and safety of dendrimers of different end-terminal functionality (carboxylated vs. pyrrolidonated) by two phenotypically different human endothelial cell types (the human brain capillary endothelial cell line hCMEC/D3 and human umbilical vein endothelial cells), and without interference of the fluorophore in uptake processes. The results demonstrate comparable uptake kinetics and a predominantly clathrin-mediated endocytotic mechanism, irrespective of dendrimer end-terminal functionality, where the majority of dendrimers are directed to the endo-lysosomal compartments in both cell types. A minor fraction of dendrimers, however, localize to endoplasmic reticulum and the Golgi apparatus, presumably through the recycling endosomes. In contrast to amino-terminated PAMAM dendrimers, we confirm safety of carboxylic acid- and pyrrolidone-terminated PAMAM dendrimers through determination of cell membrane integrity and comprehensive respiratory profiling (measurements of mitochondrial oxidative phosphorylation and determination of its coupling efficiency). Our dendrimer core-labelling approach could provide a new conceptual basis for improved understanding of dendrimer performance within biological settings.
α-Synuclein Dimers as Potent Inhibitors of Fibrillization
Kyriukha, Yevhenii A.,Afitska, Kseniia,Kurochka, Andrii S.,Sachan, Shubhra,Galkin, Maksym,Yushchenko, Dmytro A.,Shvadchak, Volodymyr V.
, (2019/11/14)
Aggregation of the neuronal protein α-synuclein into amyloid fibrils plays a central role in the development of Parkinson's disease. Growth of fibrils can be suppressed by blocking fibril ends from their interaction with monomeric proteins. In this work, we constructed inhibitors that bind to the ends of α-synuclein amyloid fibrils with very high affinity. They are based on synthetic α-synuclein dimers and interact with fibrils via two monomeric subunits adopting conformation that efficiently blocks fibril elongation. By tuning the charge of dimers, we further enhanced the binding affinity and prepared a construct that inhibits fibril elongation at nanomolar concentration (IC50 ≈ 20 nM). To the best of our knowledge, it is the most efficient inhibitor of α-synuclein fibrillization.
Selective fluorescent nonpeptidic antagonists for vasopressin V2 GPCR: Application to ligand screening and oligomerization assays.
Loison, Stéphanie,Cottet, Martin,Orcel, Hélène,Adihou, Hélène,Rahmeh, Rita,Lamarque, Laurent,Trinquet, Eric,Kellenberger, Esther,Hibert, Marcel,Durroux, Thierry,Mouillac, Bernard,Bonnet, Dominique
supporting information, p. 8588 - 8602 (2013/01/15)
A series of fluorescent benzazepine ligands for the arginine-vasopressin V2 receptor (AVP V2R) was synthesized using "Click" chemistry. Their in vitro pharmacological profile at AVP V2R, V1aR, V1bR, and oxytocin receptor was measured by binding assay and functional studies. Compound 9p, labeled with Lissamine Rhodamine B using novel solid-phase organic tagging (SPOrT) resin, exhibited a high affinity for V2R (4.0 nM), an excellent selectivity toward V2R and antagonist properties. By changing the nature of the dye, DY647 and Lumi4-Tb probes 44 and 47 still display a high affinity for V2R (5.6 and 5.8 nM, respectively). These antagonists constitute the first high-affinity selective nonpeptidic fluorescent ligands for V 2R. They enabled the development of V2R time-resolved FRET-based assay readily amenable to high-throughput screening. Taking advantage of their selectivity, these compounds were also successfully involved in the study of V1aR-V2R dimerization on cell surface.
