The therapeutic potential of fungal ribotoxins

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 inhibi...

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Detalles Bibliográficos
Autores: Carreras Sangrà, Nelson, Álvarez García, Elisa, Herrero Galán, Elías, Tomé, Jaime, Lacadena García-Gallo, Francisco Javier, Alegre Cebollada, Jorge, Oñaderra, Mercedes, Gavilanes, José G., Martínez Del Pozo, Álvaro
Tipo de recurso: artículo
Fecha de publicación:2008
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/52957
Acceso en línea:https://hdl.handle.net/20.500.14352/52957
Access Level:acceso abierto
Palabra clave:Asp f 1
Fungal allergy
Immunotoxin
Restrictocin
RNase
Sarcin
Farmacología (Farmacia)
Medicamentos
Bioquímica (Biología)
Biotecnología
Biología molecular (Biología)
3209 Farmacología
2302 Bioquímica
3399 Otras Especialidades Tecnológicas
2415 Biología Molecular
Descripción
Sumario: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.