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Natural and engineered ribonucleases as potential cancer therapeutics

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Abstract

By reason of their cytotoxicity, ribonucleases (RNases) are potential anti-tumor drugs. Particularly members from the RNase A and RNase T1 superfamilies have shown promising results. Among these enzymes, Onconase, an RNase from the Northern Leopard frog, is furthest along in clinical trials. A general model for the mechanism of the cytotoxic action of RNases includes the interaction of the enzyme with the cellular membrane, internalization, translocation to the cytosol, and degradation of ribonucleic acid. The interplay of these processes as well as the role of the thermodynamic and proteolytic stability, the catalytic activity, and the capability of the RNase to evade the intracellular RNase inhibitor has not yet been fully elucidated. This paper discusses the various approaches to exploit RNases as cytotoxic agents.

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Acknowledgements

The Land Sachsen-Anhalt is gratefully acknowledged for supporting this work (3537C/0903T).

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Authors and Affiliations

  1. Department of Biochemistry/Biotechnology, Martin-Luther University, Kurt-Mothes-Strasse 3, 06120, Halle, Germany

    Ulrich Arnold & Renate Ulbrich-Hofmann

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  1. Ulrich Arnold
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  2. Renate Ulbrich-Hofmann
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Correspondence to Ulrich Arnold.

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Arnold, U., Ulbrich-Hofmann, R. Natural and engineered ribonucleases as potential cancer therapeutics. Biotechnol Lett 28, 1615–1622 (2006). https://doi.org/10.1007/s10529-006-9145-0

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