| Autor: |
Morin, K. W., Atrazheva, E. D., Knaus, E. E., Wiebe, L. I. |
| Zdroj: |
Journal of Medicinal Chemistry; July 4, 1997, Vol. 40 Issue: 14 p2184-2190, 7p |
| Abstrakt: |
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 (10−13) 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. |
| Databáze: |
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