Peptides toxins

One peptide toxin from the mushroom Amanita phalhides, a-amanitin, is a specific differential inhibitor of the eukaryotic nuclear DNA-dependent RNA polymerases and as such has proved to be a powerful research tool (Table 37-2). a-Amanitin blocks the translocation of RNA polymerase during transcription. 

Figure 8. A schematic for the toxin binding sites on the voltage-gated Na channel. Toxin-free open and closed conformations are drawn at the left and center. Separate sites are depicted within the membrane for activators such as BTX, VTD (A), and brevetoxin (B) these are coupled to each other and to the a-peptide toxin site (a), which is kinetically linked to the -peptide toxin site (P see ref. 20). Near the outer opening of the pore is a site (G) for STX and TTX which is affected by binding at site A and which can modify inactivation gating.

The cellular/molecular mechanism of action for these cyclic peptide toxins is now an area of active research in several laboratories. These peptides cause striking ultrastructural changes in isolated hepatocytes (95) including a decrease in the polymerization of actin. This effect on the cells cytoskeletal system continues to be investigated and recent work indirectly supports the idea that these toxins interact with the cells cytoskeletal system (86,96). Why there is a specificity of these toxins for liver cells is not clear although it has been suggested that the bile uptake system may be at least partly responsible for penetration of the toxin into the cell (92). 

Work with European toxic cyanobacteria was partially supported by a NATO collaborative research grant between W.W. Carmichael and G.A. Codd, University of Dundee, Scotland, and O.M. Skulberg, Norwegian Water Research Institute, Oslo, Norway. Toxin structure work on European and North American peptide toxins is supported in part by U.S. AMRDC contract DAMD17-87-C-7019 to W.W. Carmichael. Portions of the work represent part of the Ph.D. dissertation research of N.A. Mahmood and E.G. Hyde. Their work was supported in part by fellowship support from the Biomedical Ph.D. Program, Wright State University. 

Using this approach, EGF has been successfully conjugated by disulfide exchange to the A chain of diphtheria toxin (Shimisu et al., 1980). A cystaminyl derivative of insulin also could be conjugated to the A chain of diphtheria toxin by this method (Miskimins and Shimizu, 1979). Other references to disulfide exchange using cystamine include Oeltmann and Forbes (1981) and Bacha et al. (1983) who prepared antibody-toxin and peptide-toxin conjugates, respectively. 

Cyproase 1 is in effect a new enzyme, produced by systematic protein engineering firmly based on sound chemical principles. Its status as an enzyme mimic may be debatable its efficiency is not. It was shown to hydrolyze 25% of bonds to proline in a (denatured) peptide toxin in two hours at pH 70, with some 400 turnovers. It is one of the two most efficient enzyme mimics we will encounter in this article1131... 

Plant Peptide Toxins from Nonmarine Environments... 

Plant Peptide Toxins in Biotechnoiogy and Pharmaceuticai Appiications 278... 

Plant Peptide Toxins as Pharmaceutical Tools and Agents 279... 

Describing the whole kingdom of plant defense peptides in depth is beyond the scope of this chapter. In this section a few more peptide toxin activities implied in plant defense will be mentioned that do not fit into the categories mentioned before. 

Plant Peptide Toxins in Biotechnology and Pharmaceutical Applications... 

---