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Selective targeting of 2'-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro

Journal Article


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 esterl abile 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.

Publication Date


  • 2010

Citation


  • Vine, K. L., Locke, J. M.., Bremner, J. B., Pyne, S. G. & Ranson, M. (2010). Selective targeting of 2'-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro. Bioorganic and Medicinal Chemistry Letters, 20 (9), 2908-2911.

Scopus Eid


  • 2-s2.0-77950865527

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/5043

Number Of Pages


  • 3

Start Page


  • 2908

End Page


  • 2911

Volume


  • 20

Issue


  • 9

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 esterl abile 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.

Publication Date


  • 2010

Citation


  • Vine, K. L., Locke, J. M.., Bremner, J. B., Pyne, S. G. & Ranson, M. (2010). Selective targeting of 2'-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro. Bioorganic and Medicinal Chemistry Letters, 20 (9), 2908-2911.

Scopus Eid


  • 2-s2.0-77950865527

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/5043

Number Of Pages


  • 3

Start Page


  • 2908

End Page


  • 2911

Volume


  • 20

Issue


  • 9