Enzymatic cleavage of peptide-linked radiolabels from immunoconjugates

James J. Peterson, Claude F. Meares

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We have incorporated peptides selected by combinatorial library [Peterson, J.J., and Meares, C.F. (1998) Bioconjugate Chem. 9, 618-626) into peptide-linked radiolabeled immunoconjugates of the form DOTA-peptide-antibody. Decapeptide linkers -GFQGVQFAGF- and -GFGSVQFAGF-, selected for cleavage by human liver cathepsin B, were rapidly digested in vitro when compared to the simple model tetrapeptide motif of the prototype -GGGF- [Li, M., and Meares, C.F. (1993) Bioconjugate Chem. 4, 275-283]. Cleavage properties of these library-selected substrates for cathepsin B compared favorably with decapeptide linkers -GLVGGAGAGF- and -GGFLGLGAGF-, which incorporate two of the most labile extended cathepsin B substrates from the literature. The decapeptide linker -GFGSTFFAGF-, selected from the library for cleavage by human liver cathepsin D, was rapidly digested by cathepsin D while the others were not.

Original languageEnglish (US)
Pages (from-to)553-557
Number of pages5
JournalBioconjugate Chemistry
Volume10
Issue number4
DOIs
StatePublished - Jul 1999

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ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

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