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

作者：Lovitt Carrie J; Hilko David H; Avery Vicky M; Poulsen Sally Ann^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(18): 4272-4280.

DOI：10.1016/j.bmc.2016.07.021

• Chemical probe
• Cell proliferation
• Thymidine
• Pro-label
• DNA replication
• Prodrug
• Nucleoside

A common method of evaluating cellular proliferation is to label DNA with chemical probes. 5-Ethynyl-20-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.

• 出版日期2016-9-15