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Cathepsin Substrates as Cleavable Peptide Linkers in Bioconjugates, Selected from a Fluorescence Quench Combinatorial Library

1998; American Chemical Society; Volume: 9; Issue: 5 Linguagem: Inglês

10.1021/bc980059j

1520-4812

Jim Peterson, Claude F. Meares,

Protease and Inhibitor Mechanisms

Several extended peptide substrates for the human liver enzymes cathepsin B and cathepsin D have been selected as cleavable linkers for lysosomal proteolysis of bioconjugates. A one-bead-one-peptide combinatorial library of 94 fluorogenic substrates was employed. We designed this library to explore a set of substrates containing nonionizable/nonoxidizable groups to meet the requirements of prelabeling [Li et al. (1994) Bioconjugate Chem. 5, 101−104] as well as to yield stable conjugates whose preparation is straightforward.