Cephalosporin prodrugs of paclitaxel for immunologically specific activation by L-49-sFv-beta-lactamase fusion protein.
Paclitaxel conjugates of 7-phenylacetamidocephalosporanic acid were prepared as prodrugs for site specific activation by targeted beta-lactamase. Immunologically specific activation of the prodrug 5 containing 3,3-dimethyl-4-amino-butyric acid as linker in combination with the fusion protein L-49-sFv-beta-lactamase was demonstrated in vitro on 3677 melanoma cells.
Vrudhula
Vivekananda M
VM
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. vivekananda.vrudhula@bms.com
Kerr
David E
DE
Siemers
Nathan O
NO
Dubowchik
Gene M
GM
Senter
Peter D
PD
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008546:Melanoma, Experimental / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D065093:beta-Lactamase Inhibitors; C108272:L49-sFv-beta-lactamase; D001618:beta-Lactamases; D017239:Paclitaxel