1. Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective Bioimaging Probes.
- Author
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Camodeca C, Nuti E, Tosetti F, Poggi A, D'Arrigo C, Zocchi MR, and Rossello A
- Subjects
- ADAM10 Protein antagonists & inhibitors, ADAM17 Protein antagonists & inhibitors, Amyloid Precursor Protein Secretases antagonists & inhibitors, Antigens, CD metabolism, Carbocyanines chemistry, Cell Adhesion Molecules, Neuronal metabolism, Cell Line, Tumor, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Enzyme Inhibitors metabolism, Fetal Proteins metabolism, Fluorescein-5-isothiocyanate chemistry, Fluorescence, Fluorescent Dyes chemical synthesis, Fluorescent Dyes chemistry, Fluorescent Dyes metabolism, Humans, Membrane Proteins antagonists & inhibitors, Mesenchymal Stem Cells drug effects, Microscopy, Confocal methods, Microscopy, Fluorescence methods, Organogold Compounds chemical synthesis, Organogold Compounds chemistry, Organogold Compounds metabolism, Organogold Compounds pharmacology, Tumor Necrosis Factor-alpha metabolism, ADAM10 Protein metabolism, ADAM17 Protein metabolism, Amyloid Precursor Protein Secretases metabolism, Enzyme Inhibitors pharmacology, Fluorescent Dyes pharmacology, Membrane Proteins metabolism
- Abstract
A disintegrin and metalloproteinase (ADAMs) are membrane-bound metalloproteases responsible for the ectodomain shedding of various transmembrane proteins and play important roles in multiple relevant biological processes. Their altered expression is involved in several pathological conditions, and in particular ADAM10 or ADAM17 overexpression is found in various forms of cancer. To better understand how they are regulated in the cellular context, it is useful to visualize the specific ADAMs pathway by means of molecular imaging techniques. For this purpose, we synthesized bioactive fluorescent probes suitable for cell imaging and that are able to specifically target ADAM10 or ADAM17. Two previously developed ADAM17- and ADAM10-selective inhibitors were chosen for conjugation, respectively, to a Cy5.5 dye and to Cy5.5 and FITC dyes. Herein we also report the synthesis of a gold-labeled compound as an additional bioimaging probe for ADAM10. The newly synthesized ligands were found to be active in vitro on human recombinant ADAM10 and/or ADAM17, showing IC
50 values in the nanomolar range and a good selectivity over matrix metalloproteinases (MMPs). Finally, these newly developed probes were successfully used for ADAMs staining on different lymphoma cell lines and lymph node mesenchymal stromal cells., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2018
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