Catalytic bioscavengers

Curtin, B.F., Seetharam, K.I., Dhoieam, P., Gordon, R.K., Doctor, B.P., Nambiar, M.P. (2008). Resveratrol induces catalytic bioscavenger paraoxonase 1 expression and protects against chemical warfare nerve agent toxicity in human cell lines. J. Cell. Biochem. 103 1054-35. 

TABLE 69.3. Kinetic characterization of catalytic bioscavengers and the vascular concentration of 1 LDso of the OP neurotoxicants... 

Catalytic Bioscavengers The Next Generation of Bioscavenger-Based Medical Countermeasu res... 

Certain ChE mutants sensitive to OPs do not age after phosphylation they are fully reactivatable (cf Figure 70.1, reaction 3). Such ChE mutants when associated with oximes (e.g. 2-PAM, HI-6) act as pseudocatalysts in displacing the OP moiety boimd to the enzyme. These enzyme-reactivator coupled systems could lead to a new family of pseudo-catalytic bioscavengers (Kovarik et al, 2007 Taylor et al, 2007). 

These enzymes are promising for destruction of chemical weapons stockpiles, soil remediation, decontamination of materials, protective equipment, and water polluted by pesticides and nerve agents (Russel et al, 2003). In particular, phosphorothiolates such as VX are relatively resistant to PTE. Thus, oxidative cleavage of the P-S bond could be achieved by oxidases like laccases. These enzymes could be used in association with other OP-degrading enzymes for skin decontamination or in topical skin protection formulations. Though no work has been performed on combined action of oxidases and hydrolases, oxidation of P-bonded alkyl/aryl chains by oxidases is expected to alter enantio-selectivity of PTE for parent OPs, and therefore to improve the efficiency of catalytic bioscavengers. 

Catalytic bioscavengers will be part of the arsenal of medical countermeasures for prophylaxis and treatments of OP poisoning in the very near future. Next, gene therapy will offer the possibility of transitory production of humanized OP-degrading enzymes in the body. Multiple enzyme associations will be part of active topical skin protectants and decontamination tools. 

A promising advance was made with the application of gene therapy for introducing catalytic and stoichiometric bioscavengers in vivo. It was shown that recombinant adenoviruses containing genes for Hu PONl when administered into mice boosted PONl levels in blood. Similarly, the... 

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