Saporin

Gerashchenko, D., Salin-Pascual, R. Shiromani, P. J. (2001). Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta. Brain Res. 913, 106-15. 

Kapas, L., Obal, F. Jr., Book, A. A. et al. (1996). The effects of immunolesions of nerve growth factor-receptive neurons by 192 IgG-saporin on sleep. Brain Res. 712, 53-9. 

Waite, J. J., Wardlow, M. L., Chen, A. C. et at (1994). Time course of cholinergic and monoaminergic changes in rat brain after immunolesioning with 192 IgG-saporin. Neurosci Lett. 169 (1-2), 154-8. 

Cytotoxic drugs including toxins such as saporin, ricin A chain, vinca alkaloids, and radioisotopes have been delivered to tumour cells with BsMAbs that bind to the drug/toxin with one arm and to a surface molecule on the targeted cell with the other arm. This approach has proven successful in animals as e.g. shown by Schmidt et al. [78]. 

Lesions of the basal forebrain cholinergic system using a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) result in impaired attentional, but not mnemonic, function in rats (Muir et al., 1995) and monkeys (Voytko et al., 1994), an effect which has been confirmed using more selective IgG-saporin lesions (Baxter et al., 1995 Everitt 8c Robbins, 1997). 

RIPs are plant protein toxins that are able to inhibit enzymatically ribosomal activity and are therefore highly cytotoxic [98]. RIPs are taken up in the cells by means of endocytosis, and only a small fraction (5% or less) are translocated to the cytosol where the toxins inhibit the protein synthesis and eventually kill the cell. PCI may be used to increase both the efficacy and specificity of these toxins. RIPs are divided into two groups, type I and type II. Type II RIPs, like ricin, consists of two polypeptide chains, one cytotoxic A-chain with /V-glycosidase activity and one B-chain which binds to the cell surface. Type I RIPs, like gelonin, agrostin, and saporin, lack the B chain, which make them poorly transported over the cell- and intracellular membranes to the cell cytosol. Hence, the cytotoxic effect of these protein toxins is usually absent or very low. A considerable cytotoxic effect of type I RIPs has been shown in combination with PCI, both in vitro and in vivo [25, 99]. 

Saporin-conjugated anti-human antibody (Hum-ZAP, Advanced Targeting Systems, San Diego, CA)... 

McDonald, J. R., Ong, M., Shen, C., Parandoosh, Z., Sosnowski, B., Bussel, S., and Houston, L. L. (1996). Large scale purification and characterization of recombinant fibroblast growth factor-saporin mitotoxin. Protein Express. Purif. 8, 97-108. 

Saponaria Saporin-L 1 Saponaria officinalis PAG (rRNA, DNA, poly A)... 

Saponaria Saporin-R3 Saponaria officinalis RAG (28S rRNA) PSI (RRL, insect,... 

Blakey, D.C., Skilleter, D.N., Price, R.J., Watson, G.J., Hart, L.I., Newell, D.R., Thorpe, P.E. (1988). Comparison of the pharmacokinetics and hepatotoxic effects of saporin and ricin A-chain immunotoxins on murine liver parenchymal cells. Cancer Res. 48 7072-8. 

Fig. 3.3 shows the principle behind the design of immunotoxins. A number of protein toxins of bacterial and plant origin are useful for the production of immunotoxins. These include the diphtheria toxin and pseudomonas exotoxin from bacteria, and ricin, arbin, pokeweed antiviral proteins, saporin, and gelonin from plants (Pastan et al, 1986 Pastan and FitzGerald, 1991). All of these toxins kill cells by entering the cells, and enzymatically inactivating the translational machinery of the cells. Some, such as diphtheria toxin, arbin, and ricin, are composed of two protein chains, A and B. The B chains bind to the cell-surface... 

---