4′-Thio-5-Ethyl-2′-Deoxyuridine5′-Triphosphate (TEDUTP): Synthesis and Substrate Properties in DNA-Synthesizing Systems

Abstract

An efficient synthesis of the 5′-phosphate and 5′-triphosphate of a 4′-thio-2′-deoxynucleoside is described for the first time. The 5′-triphosphate of the antiherpesvirus agent 4′-thio-5-ethyl-2′-deoxyuridine (TEDU) has been shown to be a good substrate for human placental DNA polymerase α, calf thymus terminal deoxynucleotidyl transferase, and the reverse transcriptases of human immunodeficiency virus and avian myeloblastosis virus. As it is known that TEDU is a substrate only for herpesvirus-encoded thymidine kinases and not the cellular kinases, it is likely that the utilization of TEDUTP by DNA-synthesizing enzymes results in the selective toxicity seen in vitro in herpesvirus-infected cells.