3-(2-pyridyldithio)propionic acid hydrazide as a cross-linker in the formation of liposome-antibody conjugates

Bioconjug Chem. 1996 Jul-Aug;7(4):490-6. doi: 10.1021/bc960036+.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism*
  • Cross-Linking Reagents / pharmacology*
  • Dithiothreitol / pharmacology
  • Humans
  • Hydrazines / pharmacology*
  • Immunoconjugates*
  • Immunoglobulin G / metabolism
  • Liposomes / metabolism*
  • Mice
  • Models, Molecular
  • Pyridines / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antibodies
  • Cross-Linking Reagents
  • Hydrazines
  • Immunoconjugates
  • Immunoglobulin G
  • Liposomes
  • Pyridines
  • S-(2-thiopyridyl)mercaptopropionohydrazide
  • Dithiothreitol