117626-99-0Relevant articles and documents
New synthetic route to ethynyl-dUTP: A means to avoid formation of acetyl and chloro vinyl base-modified triphosphates that could poison SELEX experiments
R?thlisberger, Pascal,Levi-Acobas, Fabienne,Hollenstein, Marcel
, p. 897 - 900 (2017)
5-Ethynyl-2′-deoxyuridine is a common base-modified nucleoside analogue that has served in various applications including selection experiments for potent aptamers and in biosensing. The synthesis of the corresponding triphosphates involves a mild acidic deprotection step. Herein, we show that this deprotection leads to the formation of other nucleoside analogs which are easily converted to triphosphates. The modified nucleoside triphosphates are excellent substrates for numerous DNA polymerases under both primer extension and PCR conditions and could thus poison selection experiments by blocking sites that need to be further modified. The formation of these nucleoside analogs can be circumvented by application of a new synthetic route that is described herein.
Development of ethynyl-2′-deoxyuridine chemical probes for cell proliferation
Lovitt, Carrie J.,Hilko, David H.,Avery, Vicky M.,Poulsen, Sally-Ann
, p. 4272 - 4280 (2016/08/23)
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.
Synthesis and Antiviral Activity of Phosphonoacetic and Phosphonoformic Acid Esters of 5-Bromo-2'-deoxyuridine and Related Pyrimidine Nucleosides and Acyclonucleosides
Lambert, Robert W.,Martin, Joseph A.,Thomas, Gareth J.,Duncan, Ian B.,Hall, Michael J.,Heimer, Edgar P.
, p. 367 - 374 (2007/10/02)
Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters.The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride.Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester (59).Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2.The BUdR-PAA derivative (7) and the BUdR-PFA derivative (59) were highly active, especially the latter, which was more active than the parent nucleoside BUdR (3) against the type 2 virus.The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.
