6533b823fe1ef96bd127e3ca
RESEARCH PRODUCT
Fluorescent Probes for Ecto-5′-nucleotidase (CD73)
Karolina LosenkovaRiham M. IdrisYulu WangLaura SchäkelChristian RennConstanze C. SchmiesGeorg RolshovenGennady G. YegutkinFrancesca GarofanoChrista E. MüllerHaneen Al-hroubIngo G.h. Schmidt-wolfHerbert Zimmermannsubject
Adenosinemedicine.medical_treatmentInflammation01 natural sciencesBiochemistryecto-5′-nucleotidaseHydrolysisDrug Discoverymedicine010405 organic chemistryChemistryfungiOrganic ChemistryEcto 5 nucleotidase cd73ImmunotherapyAdenosineFluorescence0104 chemical sciences010404 medicinal & biomolecular chemistryBiochemistryCancer cellCD73fluorescenceimmunotherapymedicine.symptominflammation.medicine.drugdescription
[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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-09-03 | ACS Medicinal Chemistry Letters |