title: The targeting of agmatine-liganded mitomycin C to an enzyme on the surface of tumour cells.
abstract: Tumour cells possess a cell surface protease referred to as guanidinobenzoatase (GB). We have synthesised a liganded form of mitomycin C which we refer to as MMC*. This MMC* has the fluorescent properties of mitomycin C and the additional ability to be directed to the active centre of GB by the agmatine moiety of the ligand. We have demonstrated the selective delivery of MMC* to the cell surface of tumour cells possessing active GB by fluorescent microscopy and competition experiments with molecules known to bind to the active centre of GB. The MMC* has a high affinity for tumour cell surface GB and we hope it may have potential in the selective delivery of mitomycin C in the chemotherapy of tumours in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Manchester, U.K.
authors.forename: F S
authors.initials: FS
authors.lastname: Steven
authors.forename: M M
authors.initials: MM
authors.lastname: Griffin
authors.forename: I C
authors.initials: IC
authors.lastname: Talbot
mesh_terms: D000376:Agmatine / Q000031:analogs & derivatives* / Q000378:metabolism; D000585:Aminacrine / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D010450:Endopeptidases; D006146:Guanidines / Q000031:analogs & derivatives*; D006651:Histocytochemistry; D007668:Kidney / Q000473:pathology*; D007942:Leukemia, Experimental / Q000201:enzymology* / Q000473:pathology; D008856:Microscopy, Fluorescence; D016685:Mitomycin; D008937:Mitomycins / Q000378:metabolism*; D051381:Rats; D013386:Succinates / Q000378:metabolism*; D019802:Succinic Acid
chemical_list: D006146:Guanidines; D008937:Mitomycins; D013386:Succinates; D016685:Mitomycin; D000376:Agmatine; D000585:Aminacrine; D019802:Succinic Acid; D002265:Carboxylic Ester Hydrolases; C037288:guanidinobenzoate esterase; D010450:Endopeptidases