Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack

Toxins

Maddalena de Virgilio¹  Alessio Lombardi³  Rocco Caliandro² 

[1] Istituto di Genetica Vegetale, Consiglio Nazionale delle Ricerche, Bari, Italy;Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Bari, Italy;Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche, Milan, Italy;

关键词: ribosome-inactivating proteins;    cancer immunotherapy;    ITs;    vascular leak syndrome;    recombinant expression;    fusion toxins;    single chain antibody variable fragments;    Pichia pastoris;   

DOI  :  10.3390/toxins2112699

来源: mdpi

【 摘 要 】

Ribosome-inactivating proteins (RIPs) are EC3.2.32.22 N-glycosidases that recognize a universally conserved stem-loop structure in 23S/25S/28S rRNA, depurinating a single adenine (A4324 in rat) and irreversibly blocking protein translation, leading finally to cell death of intoxicated mammalian cells. Ricin, the plant RIP prototype that comprises a catalytic A subunit linked to a galactose-binding lectin B subunit to allow cell surface binding and toxin entry in most mammalian cells, shows a potency in the picomolar range. The most promising way to exploit plant RIPs as weapons against cancer cells is either by designing molecules in which the toxic domains are linked to selective tumor targeting domains or directly delivered as suicide genes for cancer gene therapy. Here, we will provide a comprehensive picture of plant RIPs and discuss successful designs and features of chimeric molecules having therapeutic potential.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland.