Cell-surface glycoconjugates and ribosomes

This target refers to a dual-site mechanism of action typically associated with Type II ribosome-inactivating proteins (RIPs), such as mistletoe lectins (e.g., Aviscumine) and ricin. The process begins with the drug's B-chain binding to cell-surface glycoconjugates, specifically glycoproteins or glycolipids containing terminal galactose or N-acetylgalactosamine residues, which are often overexpressed on tumor and activated immune cells (Büssing et al., 1996). Following receptor-mediated endocytosis and retrograde transport, the A-chain is released into the cytosol where it targets the ribosome. Specifically, it acts as an RNA N-glycosidase, depurinating a specific adenine residue (A4324 in humans) within the sarcin/ricin loop of the 28S ribosomal RNA, which irreversibly halts protein synthesis and triggers apoptosis (Stirpe & Battelli, 2006). This dual targeting is particularly relevant in oncology and immunology, as tumor cells often overexpress specific glycoconjugates, and the subsequent inhibition of protein synthesis leads to apoptosis. Drugs like Aviscumine exploit this pathway to induce cell death in malignant cells while modulating immune responses through the release of cytokines from treated immune cells (Schöffski et al., 2004).

Other names

Glycan-ribosome target systemMistletoe lectin targetsType II ribosome-inactivating protein targetsGalactose-binding sites and 28S rRNA

Binding to cell-surface glycoconjugates (lectin-carbohydrate interaction) followed by translocation to the cytosol and site-specific depurination of 28S rRNA, leading to protein synthesis inhibition.