Fluorescent Probes for Ecto-5′-nucleotidase (CD73)
| Autor: | Karolina Losenkova, Riham M. Idris, Yulu Wang, Laura Schäkel, Christian Renn, Constanze C. Schmies, Georg Rolshoven, Gennady G. Yegutkin, Francesca Garofano, Christa E. Müller, Haneen Al-Hroub, Ingo G.H. Schmidt-Wolf, Herbert Zimmermann |
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| Přispěvatelé: | Schmies C.C., Rolshoven G., Idris R.M., Losenkova K., Renn C., Schakel L., Al-Hroub H., Wang Y., Garofano F., Schmidt-Wolf I.G.H., Zimmermann H., Yegutkin G.G., Muller C.E. |
| Rok vydání: | 2020 |
| Předmět: |
Adenosine
medicine.medical_treatment Inflammation 01 natural sciences Biochemistry ecto-5′-nucleotidase Hydrolysis Drug Discovery medicine 010405 organic chemistry Chemistry fungi Organic Chemistry Ecto 5 nucleotidase cd73 Immunotherapy Fluorescence 0104 chemical sciences 010404 medicinal & biomolecular chemistry Cancer cell CD73 fluorescence immunotherapy medicine.symptom inflammation medicine.drug |
| Zdroj: | ACS Med Chem Lett |
| ISSN: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.0c00391 |
| Popis: | [Image: see text] Ecto-5′-nucleotidase (CD73) catalyzes the hydrolysis of AMP to anti-inflammatory, immunosuppressive adenosine. It is expressed on vascular endothelial, epithelial, and also numerous cancer cells where it strongly contributes to an immunosuppressive microenvironment. In the present study we designed and synthesized fluorescent-labeled CD73 inhibitors with low nanomolar affinity and high selectivity based on N(6)-benzyl-α,β-methylene-ADP (PSB-12379) as a lead structure. Fluorescein was attached to the benzyl residue via different linkers resulting in PSB-19416 (14b, K(i) 12.6 nM) and PSB-18332 (14a, K(i) 2.98 nM) as fluorescent high-affinity probes for CD73. These compounds are anticipated to become useful tools for biological studies, drug screening, and diagnostic applications. |
| Databáze: | OpenAIRE |
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