121563-65-3Relevant articles and documents
Synthesis and cellular uptake of 2'-substituted analogues of (e)-5-(2- [125i]iodovinyl)-2'-deoxyuridine in tumor cells transduced with the herpes simplex type-1 thymidine kinase gene. Evaluation as probes for monitoring gene therapy
Morin, Kevin W.,Atrazheva, Elena D.,Knaus, Edward E.,Wiebe, Leonard I.
, p. 2184 - 2190 (1997)
A useful synthetic methodology was developed to synthesize and radiolabel a series of (E)-5(2-[125I)iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (HSV-1 TK). (E)- 5-(2-[125I]Iodovinyl)-2'-deoxyuridine ([125I]IVDU, 10), (E)-5-(2- [125I]iodovinyl)2'-fluoro-2'-deoxyuridine ([125I]IVFRU, 11), (E)-5-(2- [125I]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([125I]IVFAU, 12), and (E)-5-(2-[125I]iodovinyl)arabinouridine ([125I]IVAU, 13) were synthesized in 63-83% radiochemical yield by reaction of the unprotected (E)- 5-(2-(trimethylsilyl)vinyl) precursors (6-9)with [125I]ICl. Cellular uptake of these labeled compounds (1018) was evaluated in vitro. All compounds showed minimal uptake in the KBALB cell line. However, increased uptake was observed for all compounds in KBALB-STK cells which are transduced with a replication incompetent Moloney murine leukemia virus vector encoding the HSV-1 TK gene. The results indicate that uptake of these compounds in KBALB-STK cells is variable and highly dependent on the nature of the sugar 2'-substituent. When a fluoro (12) or a hydroxy (13) substituent is present in the arabinofuranosyl (up) configuration at the 2'-position, there is diminished cellular uptake in KBALB-STK cells relative to hydrogen (10) or fluorine (11) in the ribofuranosyl (down) configuration at the 2'-position. Our results indicate that radiolabeled IVFRU (11) is most promising for further in vivo studies.
