Development of ethynyl-2'-deoxyuridine chemical probes for cell proliferation.

Autor: Lovitt CJ; Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia., Hilko DH; Eskitis Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia., Avery VM; Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia., Poulsen SA; Eskitis Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia. Electronic address: s.poulsen@griffith.edu.au.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2016 Sep 15; Vol. 24 (18), pp. 4272-4280. Date of Electronic Publication: 2016 Jul 12.
DOI: 10.1016/j.bmc.2016.07.021
Abstrakt: A common method of evaluating cellular proliferation is to label DNA with chemical probes. 5-Ethynyl-2'-deoxyuridine (EdU) is a widely utilized chemical probe for labeling DNA, and upon incorporation, EdU treatment of cells is followed by a reaction with a small molecule fluorescent azide to allow detection. The limitations when using EdU include cytotoxicity and a reliance on nucleoside active transport mechanisms for entry into cells. Here we have developed six novel EdU pro-labels that consist of EdU modified with variable lipophilic acyl ester moieties. This pro-label:chemical probe relationship parallels the prodrug:drug relationship that is employed widely in medicinal chemistry. EdU and EdU pro-labels were evaluated for their labeling efficacy and cytotoxicity. Several EdU pro-label analogues incorporate into DNA at a similar level to EdU, suggesting that nucleoside transporters can be bypassed by the pro-labels. These EdU pro-labels also had reduced toxicity compared to EdU.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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