Approaches to Endow Ribonucleases with Antitumor Activity: Lessons Learned from the Native Cytotoxic Ribonucleases

Typical antitumor drugs disrupt the flow of biochemical information from DNA to proteins with the aim of precluding uncontrolled cell proliferation and inducing cancer cell apoptosis. However, most of the currently used small antitumor drugs are genotoxic because they act over DNA. Pharmaceutical in...

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Detalhes bibliográficos
Autores: Castro, Jessica, Ribó i Panosa, Marc, Benito i Mundet, Antoni, Vilanova i Brugués, Maria
Formato: capítulo de livro
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/16181
Acesso em linha:http://hdl.handle.net/10256/16181
Access Level:acceso abierto
Palavra-chave:Ribonucleases
Fàrmacs antitumorals
Antitumor drugs
Bioquímica
Biochemistry
Enginyeria de proteïnes
Protein engineering
Descrição
Resumo:Typical antitumor drugs disrupt the flow of biochemical information from DNA to proteins with the aim of precluding uncontrolled cell proliferation and inducing cancer cell apoptosis. However, most of the currently used small antitumor drugs are genotoxic because they act over DNA. Pharmaceutical industry is now searching for a new line of cancer chemotherapeutics without genotoxic effectsǯ Ribonucleases (RNases) are small basic proteins, present in all life forms, which belong to this kind of chemotherapeutics. Some of them present with remarkable selective antitumor activity linked to their ability to destroy RNA, a powerful way to control gene expression, leaving DNA unharmed. In the last two decades, the knowledge gained on the cytotoxic mechanism of these RNases has been used to engineer more powerful and selective variants to kill cancer cells. In this chapter, we describe the advances reached in endowing an RNase with antitumor abilities