Ribosome Inactivating Proteins from Plants: Biological Properties and their Use in Experimental Therapy

Abstract

Ribosome-inactivating proteins (RIPs) are 28 S rRNA N-glycosidases isolated mainly from plants that irreversibly inactivate ribosomes, thereby impairing protein synthesis. In recent years, polynucleotide:adenosine N-glycosidase activity and induction of apoptosis have been reported and may have a particular significance. There are two classes of RIPs: type 1 RIPs, consisting of single-chain proteins, and type 2 RIPs, consisting of an A chain with RIP properties covalently linked to a B chain with lectin properties. Type 2 RIPs may be very toxic or non toxic, whereas type 1 RIPs are always non-toxic. Due to the diverse activities of RIPs, research has been conducted to investigate their use as antiviral and antitumor agents or as the toxic part of conjugates. Conjugates consist of a targeting portion such as an antibody, a lectin or a growth factor linked to a toxic portion. RIPs have been used as the toxic portion in conjugates that have been tested in several experimental therapies against various malignancies. Although some important disadvantages still need to be improved, recent clinical trials encourage the use of these conjugates as efficacious agents in the treatment of cancer and other diseases.