title: Selective targeting of 2'-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro.
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.
authors.affiliation: School of Biological Sciences and Centre for Medical Bioscience, University of Wollongong, NSW 2522, Australia. v
authors.forename: Kara L
authors.initials: KL
authors.lastname: Vine
authors.forename: Julie M
authors.initials: JM
authors.lastname: Locke
authors.forename: John B
authors.initials: JB
authors.lastname: Bremner
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Pyne
authors.forename: Marie
authors.initials: M
authors.lastname: Ranson
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D009369:Neoplasms / Q000201:enzymology; D017396:Plasminogen Activator Inhibitor 2 / Q000737:chemistry / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017396:Plasminogen Activator Inhibitor 2; C001943:5-fluorouridine; D014568:Urokinase-Type Plasminogen Activator; D014529:Uridine