The covalent linking of two nucleotide analogues to antibodies.
Two anticancer drugs, antagonists of nucleic acids, were covalently linked to antibodies specifically reactive with B leukemia cells and thus with a potential possibility of drug targeting to the tumor site. The drugs cytosine 1-beta-D-arabinoside and 5-fluorouridine, competitive inhibitors of enzymes involved in DNA synthesis, were linked to antibodies via a dextran bridge. Cytosine 1-beta-D-arabinoside was linked to periodate-oxidized dextran and fluorouridine to dextran hydrazide. The dextran derivatives were in turn linked to antibodies that recognized a specific membrane IgM on B leukemia cells. The drug-antibody conjugates maintained most of the original antigen-binding capacity of the antibody and the full pharmacological activity of the drugs.
Hurwitz
E
E
Kashi
R
R
Arnon
R
R
Wilchek
M
M
Sela
M
M
D000818:Animals; D000906:Antibodies; D003561:Cytarabine / Q000008:administration & dosage; D003911:Dextrans; D004304:Dosage Forms; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000906:Antibodies; D003911:Dextrans; D004304:Dosage Forms; D003561:Cytarabine; C001943:5-fluorouridine; D014529:Uridine