Tumor protease-activated, pore-forming toxins from a combinatorial library.

Journal article

We describe a library of two-chain molecular complementation mutants of staphylococcal alpha-hemolysin that features a combinatorial cassette encoding thousands of protease recognition sites in the central pore-forming domain. The cassette is flanked by a peptide extension that inactivates the protein. We screened the library to identify alpha-hemolysins that are highly susceptible to activation by cathepsin B, a protease that is secreted by certain metastatic tumor cells. Toxins obtained by this procedure should be useful for the permeabilization of malignant cells thereby leading directly to cell death or permitting destruction of the cells with drugs that are normally membrane impermeant.

Authors: Panchal, R; Cusack, E; Cheley, S; Bayley, J

• Publication status: Published
• Journal: Nature biotechnology
• Volume: 14
• Issue: 7
• Pages: 852-856
• Publication date: 1996-07-01
• DOI: 10.1038/nbt0796-852
• EISSN: 1546-1696
• ISSN: 1087-0156
• Language: English
• Keywords: Mutagenesis; Exotoxins; Humans; Cysteine Endopeptidases; Neoplasms; Bacterial Toxins; Cathepsin B; DNA Primers; Peptide Library; Base Sequence; Amino Acid Sequence; Hemolysin Proteins