Abstract
Ribotoxins constitute a family of toxic extracellular fungal RNases that exert a highly specific activity on a conserved region of the larger molecule of rRNA, known as the sarcin – ricin loop. This cleavage of a single phosphodiester bond inactivates the ribosome and leads to protein synthesis inhibition and cell death. In addition to this ribonucleolytic activity, ribotoxins can cross lipid membranes in the absence of any known protein receptor. This ability is due to their capacity to interact with acid phospholipid-containing membranes. Both activities together explain their cytotoxic character, being rather specific when assayed against some transformed cell lines. The determination of high-resolution structures of some ribotoxins, the characterization of a large number of mutants, and the use of lipid model vesicles and transformed cell lines have been the tools used for the study of their mechanism of action at the molecular level. The present knowledge suggests that wild-type ribotoxins or some modified variants might be used in human therapies. Production of hypoallergenic mutants and immunotoxins designed against specific tumors stand out as feasible alternatives to treat some human pathology in the mid-term future.
Keywords: Asp f 1, fungal allergy, immunotoxin, restrictocin, Rnase, α-sarcin
Current Pharmaceutical Biotechnology
Title: The Therapeutic Potential of Fungal Ribotoxins
Volume: 9 Issue: 3
Author(s): Nelson Carreras-Sangra, Elisa Alvarez-Garcia, Elias Herrero-Galan, Jaime Tome, Javier Lacadena, Jorge Alegre-Cebollada, Mercedes Onaderra, Jose G. Gavilanes and Alvaro Martinez-del-Pozo
Affiliation:
Keywords: Asp f 1, fungal allergy, immunotoxin, restrictocin, Rnase, α-sarcin
Abstract: Ribotoxins constitute a family of toxic extracellular fungal RNases that exert a highly specific activity on a conserved region of the larger molecule of rRNA, known as the sarcin – ricin loop. This cleavage of a single phosphodiester bond inactivates the ribosome and leads to protein synthesis inhibition and cell death. In addition to this ribonucleolytic activity, ribotoxins can cross lipid membranes in the absence of any known protein receptor. This ability is due to their capacity to interact with acid phospholipid-containing membranes. Both activities together explain their cytotoxic character, being rather specific when assayed against some transformed cell lines. The determination of high-resolution structures of some ribotoxins, the characterization of a large number of mutants, and the use of lipid model vesicles and transformed cell lines have been the tools used for the study of their mechanism of action at the molecular level. The present knowledge suggests that wild-type ribotoxins or some modified variants might be used in human therapies. Production of hypoallergenic mutants and immunotoxins designed against specific tumors stand out as feasible alternatives to treat some human pathology in the mid-term future.
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Carreras-Sangra Nelson, Alvarez-Garcia Elisa, Herrero-Galan Elias, Tome Jaime, Lacadena Javier, Alegre-Cebollada Jorge, Onaderra Mercedes, Gavilanes G. Jose and Martinez-del-Pozo Alvaro, The Therapeutic Potential of Fungal Ribotoxins, Current Pharmaceutical Biotechnology 2008; 9 (3) . https://dx.doi.org/10.2174/138920108784567335
DOI https://dx.doi.org/10.2174/138920108784567335 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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