Toxins chimeric

Olsnes, S., and Pihl, A. (1982b) Chimeric toxins. Pharmacol. Ther. 15, 355. 

Fujihara H, Walker LA, Gong MC et al 1997 Inhibition of RhoA translocation and calcium sensitization by in vivo ADP-ribosylation with the chimeric toxin DC3B. Mol Biol Cell... 

Pastan I, FitzGerald D. Pseudomonas exotoxin chimeric toxins. / Biol Chem 1989 264 15157-60. 

Aullo P, Giry M, Olsnes S et al. (1993) A chimeric toxin to study the role of the 21 kDa GTP binding protein rho in the control of actin microfilament assembly. In EMBO J. 12 921 -31... 

There is now a substantial literature on the synthesis and testing of chimeric molecules. These substances are each composed of at least two functional domains, such as a tissue-targeting domain and a pharmacologically active domain. One common strategy in constructing chimeric toxins is to isolate the binding domain of one toxin (e.g., diphtheria toxin) and attach this to the poisoning domain of another (e.g., ricin). This chimeric molecule attaches only to cells that have the diphtheria toxin receptor, and it expresses only the intracellular effects of ricin. 

Pastan I, FitzGerald D (1989) Pseudomonas exotoxin Chimeric toxins. J Biol Chem 264 15157-15160. 

Prior Ti, FitzGerald DJ, Pastan I (1991) Barnase toxin A new chimeric toxin composed of Pseudomonas exotoxin A and barnase. Cell 64 1017-1023. 

Olsnes, S. and Pihl, A. (1986) Construction and properties of chimeric toxins target specific cytotoxic agents, in Domer, F. and Drews, J. (Eds.) Pharmacology of Bacterial Toxins, 1st ed, Oxford, England, New York, NY, Pergamon Press. 

Seetharam, S., Chaudhary, V. K., FitzGerald, D., and Pastan, I. (1991) Increased cytotoxic activity of Pseudomonas exotoxin and two chimeric toxins ending in KDEL. J. Biol. Chem. 266, 17,376-17,381. 

Fig. 4. Phenylephrine-induced contraction in intact portal vein smooth muscle showing the effect of 48 hr treatment with DC3B, the chimeric toxin that ADP-ribosylates and inhibits the activity of endogenous RhoA. Note that the contractile response of untreated smooth muscle was biphasic, consisting of a phasic transient followed by a tonic phase. DC3B treatment inhibited the tonic phase of contraction with little effect on the initial, transient phase (P< 0.0001 from Fujihara et al. 1997).

Fig. 5. ADP-ribosylation of RhoA by DC3B inhibits GTPyS-induced RhoA translocation from the cytosolic to the membrane fraction. After incubation with or without the chimeric toxin DC3B (48 hr), a-toxin-permeabilized tissues were stimulated with GTPyS (50 pM) for 20 min and homogenized, fractionated and separated into cytosolic (C) and Triton-extracted particulate fraction (P) translocation of RhoA to the membrane fraction was inhibited by DC3B treatment (48 hr). A Representative Western blots of RhoA visualized by enhanced chemiluminescence. Arrows indicate position of mol wt markers remainder of gels did not show other bands and are not shown. B Summary of the effect of DC3B on translocation of RhoA by GTPyS (50 xM) from the cytosolic to the membrane fraction. DC3B significantlyinhibited translocation of RhoA (from Fujihara et al. 1997).

Native ricin was first shown to inhibit tumor growth in 1951. The toxin was tested by various routes—local application, intratumor, and intraarterial—in patients with tumors, with varying results.8 In recent years, with the advent of new immunotherapeutic techniques, ricin has once again found a niche in the armamentarium of the medical profession. It has been studied as a component of antitumor agents called immunotoxins or, more specifically, chimeric toxins.9... 

Leader Sequences Chimeric Toxins Mutated Toxins Promoters Stabilize mRNA Improve Translation... 

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