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

Nature Biotechnology volume 14, pages 852–856 (1996)Cite this article

Abstract

We describe a library of two-chain molecular complementation mutants of staphylococcal α-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 α-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.

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Author notes

  1. Hagan Bayley: email: bayley@sci.wfbr.edu

Authors and Affiliations

  1. Worcester Foundation for Biomedical Research, 222 Maple Ave., Shrewsbury, MA, 01545

    Rekha G. Panchal, Evelyn Cusack, Stephen Cheley & Hagan Bayley

Authors
  1. Rekha G. Panchal
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  2. Evelyn Cusack
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  3. Stephen Cheley
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  4. Hagan Bayley
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Panchal, R., Cusack, E., Cheley, S. et al. Tumor protease-activated, pore-forming toxins from a combinatorial library. Nat Biotechnol 14, 852–856 (1996). https://doi.org/10.1038/nbt0796-852

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