Fluorescent Probes for Ecto-5 '-nucleotidase (CD73)

: Schmies CC, Rolshoven G, Idris RM, Losenkova K, Renn C, Schakel L, Al-Hroub H, Wang YL, Garofano F, Schmidt-Wolf IGH, Zimmermann H, Yegutkin GG, Muller CE

Publisher: AMER CHEMICAL SOC

: 2020

: ACS Medicinal Chemistry Letters

: ACS MEDICINAL CHEMISTRY LETTERS

: ACS MED CHEM LETT

: 11

: 2253

: 2260

: 8

: 1948-5875

DOI: https://doi.org/10.1021/acsmedchemlett.0c00391

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-alpha,beta-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.