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

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• 作者：Carrie J. Lovitt^a ; ^&dagger ; ; David H. Hilko^b ; ^&dagger ; ; Vicky M. Avery^a ; Sally-Ann Poulsen^b ; ^{s.poulsen@griffith.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PJPIWSDNTYIHPL-GMTAPVOTSA-N ; CUFMJPLCELTJGQ-GMTAPVOTSA-N ; YYEABENPVHWRTF-IJLUTSLNSA-N ; TUPQIGGXUVUEQU-JHJVBQTASA-N ; IUUWFEJKFNPIRI-JHJVBQTASA-N ; HESLLJPIYDJDQW-JHJVBQTASA-N ; MQTJRMJIEJVYHF-RBSFLKMASA-N ; DESZKBSMZKJGFD-BRWVUGGUSA-N ; CDEURGJCGCHYFH-IWSPIJDZSA-N
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：24
• 期：18
• 页码：4272-4280
• 全文大小：1944 K

文摘

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.