title: Aldolase antibody activation of prodrugs of potent aldehyde-containing cytotoxics for selective chemotherapy.
abstract: Prodrugs of potent aldehyde analogues of the anticancer drug doxorubicin (Dox) were synthesized. These prodrugs were efficiently activated by antibody 93F3 and no drug formation was observed in the absence of 93F3 in either phosphate buffered saline or cell culture media. In the presence of antibody 93F3, these prodrugs were activated and decreased the proliferation of human cancer cells in in vitro proliferation assays.
authors.affiliation: Skaggs Institute for Chemical Biology and Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. subhash@scripps.edu
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Sinha
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Eiton
authors.initials: E
authors.lastname: Kaltgrad
authors.forename: Fujie
authors.initials: F
authors.lastname: Tanaka
authors.forename: Christoph
authors.initials: C
authors.lastname: Rader
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lerner
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017151:Antibodies, Catalytic / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D000903:Antibiotics, Antineoplastic; D017151:Antibodies, Catalytic; D007140:Immunoglobulin Fab Fragments; D011355:Prodrugs; D004317:Doxorubicin; C109536:antibody aldolase; D005634:Fructose-Bisphosphate Aldolase