Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective Bioimaging Probes

Caterina Camodeca, Elisa Nuti, Francesca Tosetti, Alessandro Poggi, Cristina D'Arrigo, Maria Raffaella Zocchi, Armando Rossello

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 IC50 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.

Original languageEnglish
Pages (from-to)2119-2131
Number of pages13
JournalChemMedChem
Volume13
Issue number19
DOIs
Publication statusPublished - 2018

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Metalloproteases
Disintegrins
Gold compounds
Coloring Agents
Gold Compounds
Biological Phenomena
Molecular imaging
Imaging techniques
Molecular Imaging
Fluorescein-5-isothiocyanate
Matrix Metalloproteinases
Mesenchymal Stromal Cells
Fluorescent Dyes
Inhibitory Concentration 50
Lymphoma
Lymph Nodes
Cells
Staining and Labeling
Ligands
Membranes

Keywords

  • ADAM inhibitors
  • fluorescent probes
  • Hodgkin's lymphoma
  • nanoparticles

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective Bioimaging Probes. / Camodeca, Caterina; Nuti, Elisa; Tosetti, Francesca; Poggi, Alessandro; D'Arrigo, Cristina; Zocchi, Maria Raffaella; Rossello, Armando.

In: ChemMedChem, Vol. 13, No. 19, 2018, p. 2119-2131.

Research output: Contribution to journalArticle

Camodeca, Caterina ; Nuti, Elisa ; Tosetti, Francesca ; Poggi, Alessandro ; D'Arrigo, Cristina ; Zocchi, Maria Raffaella ; Rossello, Armando. / Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective Bioimaging Probes. In: ChemMedChem. 2018 ; Vol. 13, No. 19. pp. 2119-2131.
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