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The therapeutic potential of fungal ribotoxins

Carreras Sangrà, Nelson and Álvarez García, Elisa and Herrero Galán, Elías and Tomé, Jaime and Lacadena, Javier and Alegre Cebollada, Jorge and Oñaderra, Mercedes and Gavilanes, José G. and Martínez del Pozo, Álvaro (2008) The therapeutic potential of fungal ribotoxins. Current Pharmaceutical Biotechnology, 9 . pp. 153-160. ISSN 1389-2010

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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.


Item Type:Article
Uncontrolled Keywords:Asp f 1, Fungal allergy, Immunotoxin, Restrictocin, RNase, Sarcin
Subjects:Medical sciences > Pharmacy > Pharmacology
Medical sciences > Pharmacy > Drugs
Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Biotechnology
Medical sciences > Biology > Molecular biology
ID Code:8093
Deposited On:03 Oct 2008 10:59
Last Modified:06 Feb 2014 07:59

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