Biotechnological Potential of Ribosome-Inactivating Proteins (RIPs)

Abstract

Ribosome-inactivating proteins (RIPs) are enzymes (E.C. 3.2.2.22) that have shown remarkable cytotoxic activity linked to their ability to inactivate protein synthesis through their N-glycosidase activity on the 28S ribosomal RNA (rRNA). They are classified as monomeric type 1 RIP and eterodimeric type 2 RIP and are widely distributed in plants, fungi, and bacteria. Many evidences suggest that they could be involved in the defense of the host against predators and viruses, without neglecting their involvement in stress response and/or nitrogen store. The studies on RIPs began at the end of the nineteenth century when ricin, a potent toxin from Ricinus communis, was identified and isolated. Since then numerous RIPs were investigated, and it has been found that their cytotoxicity is due not only to enzymatic activity but also to their intracellular routing. Their biological activity has suggested their use as potential anticancer drugs. To make selective their cytotoxicity against cancer cells, many molecular approaches have been carried out. RIPs have been linked to, or fused with, appropriate antibodies or other carriers to form "immunotoxins" or other conjugates specifically toxic to target cells of the carrier. Other strategies have been also successfully carried out using nontoxic RIPs (e.g., ebulin I and nigrin b from Sambucus species) to allow them, by using a different intracellular pathway with respect to the canonical one, to efficiently reach ribosomes. This chapter summarizes the procedures used to obtain RIPs as selective bifunctional molecules. Many generations of immune RIPs and RIP conjugates are described.