Natural and engineered ribonucleases as potential cancer therapeutics

Authors: Arnold, Ulrich; Ulbrich-Hofmann, Renate

Source: Biotechnology Letters, Volume 28, Number 20, October 2006 , pp. 1615-1622(8)

Publisher: Springer

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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.

Keywords: Ribonuclease; Cytotoxicity; Protein engineering; Stability; Cancer therapeutic

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s10529-006-9145-0

Affiliations: 1: Email: ulrich.arnold@biochemtech.uni-halle.de

Publication date: 2006-10-01