Selective targeting of 2'-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro
Kara L Vine1, Julie M Locke, John B Bremner
1School of Biological Sciences and Centre for Medical Bioscience, University of Wollongong, NSW 2522, Australia. v
Abstract:
A urokinase targeting conjugate of 2'-deoxy-5-fluorouridine (5-FUdr) was synthesized and tested for tumor-cell selective cytotoxicity in vitro. The 5-FUdr prodrug 2'-deoxy-5-fluoro-3'-O-(3-carboxypropanoyl)uridine (5-FUdrsuccOH) containing an ester-labile succinate linker was attached to the specific urokinase inhibitor plasminogen activator inhibitor type II (PAI-2) and was found to preferentially kill urokinase-over expressing cancer cells. Up to 7 molecules of 5-FUdr were incorporated per PAI-2 molecule without affecting protein activity. This is the first time a small organic cytotoxin has been conjugated to PAI-2.
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