3-(2-pyridyldithio)propionic acid hydrazide as a cross-linker in the formation of liposome-antibody conjugates.
Liposome antibody conjugates are potentially useful as a means of targeting drugs to specific tissues. A new protocol for the conjugation of IgG to maleimide-containing liposomes was developed using 3-(2-pyridyldithio)propionic acid hydrazide (PDPH) as a cross-linker. Periodate-oxidized antibody was treated with PDPH to yield a hydrazone derivative. Deprotection with DTT produced a thiolated antibody which was then conjugated to liposomes containing N-[4-(p-maleidophenyl)butyryl]-1,2-sn-distearoylphosphatidyleth anolamine. The liposome-antibody conjugates were found to have in vitro properties similar to those of conjugates formed by the traditional 3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide ester (SPDP) protocol but were cleared less rapidly in circulation. The PDPH protocol presents a viable alternative to SPDP, particularly for antibodies sensitive to amine modification.
Ansell
S M
SM
Inex Pharmaceuticals Corporation, Vancouver, British Columbia, Canada. sansell@inexpharm.com
Tardi
P G
PG
Buchkowsky
S S
SS
D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D011725:Pyridines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D003432:Cross-Linking Reagents; D006834:Hydrazines; D018796:Immunoconjugates; D007074:Immunoglobulin G; D008081:Liposomes; D011725:Pyridines; C070208:S-(2-thiopyridyl)mercaptopropionohydrazide; D004229:Dithiothreitol