Toxin inhibitors

Inhibitors/Toxins Trypsin inhibitors, aflatoxins, exotoxins (botulinum), endotoxins, PCBs, vomitoxin... 

Peptide biosynthesis may occur through two different systems. Most of cellular peptides and proteins are produced by the ribosomal machinery connecting 20 proteino-genic amino acids to the desired products. However, most of the bioactive peptides are produced non-ribosomally by large peptide synthetases. These peptides are used as antibiotics, enzyme inhibitors, toxins, and other medically useful drugs. The biosynthesis of... 

Generai.—Non-protein amino-acids have continued to attract interest during recent years not only because of their potential significance as metabolic inhibitors, toxins, intermediates in biosynthetic sequences, and taxonomic markers, but also because their interesting structmal features present numerous challenges to biosynthetic exploration. Several reviews are available dealing with the structure, distribution, and biosynthesis of free plant amino-acids. 

An enzymatic assay can also be used for detecting anatoxin-a(s). " This toxin inhibits acetylcholinesterase, which can be measured by a colorimetric reaction, i.e. reaction of the acetyl group, liberated enzymatically from acetylcholine, with dithiobisnitrobenzoic acid. The assay is performed in microtitre plates, and the presence of toxin detected by a reduction in absorbance at 410 nm when read in a plate reader in kinetic mode over a 5 minute period. The assay is not specific for anatoxin-a(s) since it responds to other acetylcholinesterase inhibitors, e.g. organophosphoriis pesticides, and would need to be followed by confirmatory tests for the cyanobacterial toxin. 

Ricin (toxin from Castor bean Ricinus communis) [A chain 96638-28-7 B chain 96638-29-8] Mr -60,000, amorphous. Crude ricin, obtained by aqueous extraction and (NH4)2S04 pptn, was chromatographed on a galactosyl-Sepharose column with sequential elution of pure ricin. The second peak was due to ricin agglutinin. [Simmons and Russell Anal Biochem 146 206 1985.) Inhibitor of protein synthesis. EXTREMELY DANGEROUS, USE EXTREME CARE [instructions accompany product]. 

Cholera toxin-induced diarrhoea 2. Increased AEA levels after administration of cholera toxin to mice, a model of diarrhoea, exert anti-secretory action in the small intestine 2. Inhibitors of cellular reuptake... 

For in vitro studies there are a number of compounds available to block protein phosphatase activity. Phosphate buffers inactivate all of these enzymes. Several naturally occurring toxins are potent inhibitors of PPPs, e.g., okadaic acid or microcystin, and are frequently used tools. PPM and PTP family members are not affected by these toxins. Vanadate containing solutions are competitive inhibitors of PTPs, pervanadate is an irreversible inhibitor of PTPs. 

Toxin (Enzyme Inhibition) Biosensors Enzyme affectors (inhibitors and activators) that influence the rate of biocatalytic reactions can also be measured. Sensing probes for organophosphate and carbamate pesticides, for the respiratory... 

Many inhibitors of substrate oxidations, substrate transport, electron transport, and ATP synthesis are known including many well-known toxins (see Sherratt, 1981 Harold, 1986 Nicholls and Ferguson, 1992). These are not discussed here except to mention specific uncouplers of oxidative phosphorylation. Classic uncouplers such as 2,4-dinitrophenol have protonated and unprotonated forms, both of which are lipid soluble and cross the inner mitochondrial membrane discharging the proton gradient. This prevents ATP synthesis and stimulates respiration. 

Soelaiman S, Wei BQ, Bergson P, Lee YS, Shen Y, Mrksich M, Shoichet BK, Tang WJ. Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough. J Biol Chem 2003 278 25990-7. 

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. 

In this scheme, EOH is the enzyme, IX is the inhibitor (either a carbamate or an organophosphate). EOH(IX) is analogous to the Michaelis Menton comploc seen with the substrate reaction. EOI is the acyl-enzyme intermediate for carbamates or a phosphoro-enzyme intermediate for the organophosphates. The equilibrium constant for this reaction (K ) is defined as k /k and the phosphorylation or carbamylation constant is defined as k2- In this study 42)y ANTX-A(S) was found to be more specific for AChE than BUChE. The double reciprocal and Dixon plot of the inhibition of electric eel AChE indicated that the toxin is a non-competitive inhibitor decreases, k remains unchanged) (Figure 2). 

Risk factors for the development of AML include exposure to environmental toxins, Hispanic ethnicity, and genetics.6 Of greater concern is the increased prevalence of AML as a secondary malignancy, resulting from chemotherapy and radiation treatment for other cancers. Alkylating agents, such as ifosfamide and cyclophosphamide, and topoisomerase inhibitors, such as etoposide, are linked to an increased risk of myelodysplastic syndrome (MDS) and AML.8... 

Chromatographic methods were extensively used to characterize the allelopathic agents. Because a great majority of the suspected toxins were already known (and several of them are ccrmercially available), simple chromatographic methods were thought to be sufficient for their characterization from the extracts. However, no detailed investigations were ever undertaken to characterize those inhibitors that may be present in minute amounts. 

The use of CL-free media required 100 times higher concentrations of the toxins for any cellular uptake. Furthermore, the entry of both toxins was denied when Vero cells were incubated in normal medium with inhibitors of CL entry, including 4-acetamido-4 -isothiocyanostilbene-2,2 -disulfonate (SITS), pyridoxal... 

Examples of inhibitors of chromatin function derived from flowering plants (Fig. 80) are etoposide (lignan) and alkaloids camptothecin, Vinca alkaloids, and 7 epitaxol. The rhizome of Podophyllum peltatum L. (May apple, Berberidaceae) has been used to remove warts and to relieve the bowels from costiveness since very early times. It contains podophyllo-toxin, a cytotoxic lignan from which etoposide (Vepesid ), which is used to treat lung cancer, lymphomas, and leukemias on account of its ability to inhibit the activity of... 

Surprisingly few studies have been performed with purified toxins. When added externally to the water, toxins of various origins were tested on the cope-pod Tigriopus californicus. The protein phosphatase inhibitor okadaic acid (17) from red tide dinoflagellates [22] and the neuronal depolarizing agent do-moic acid (10) from diatoms [40, 41] had different effects on the herbivores (Scheme 3). Micromolar concentrations of okadaic acid (17) acted both as toxin... 

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