A1 Refereed original research article in a scientific journal
Fluorescent Probes for Ecto-5 '-nucleotidase (CD73)
Authors: 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
Publication year: 2020
Journal: ACS Medicinal Chemistry Letters
Journal name in source: ACS MEDICINAL CHEMISTRY LETTERS
Journal acronym: ACS MED CHEM LETT
Volume: 11
Issue: 11
First page : 2253
Last page: 2260
Number of pages: 8
ISSN: 1948-5875
eISSN: 1948-5875
DOI: https://doi.org/10.1021/acsmedchemlett.0c00391
Abstract
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.
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.
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