Reactivation oxime-induced

The oxime-induced reactivation of organophosphorus-inhibited AChE has been modeled recently through the Density Functional Theory (DFT) approach. Two possible computed reactivation pathways of Sarin-inhibited AChE adduct by formoximate anion are shown in Scheme The two-step mechanism (Scheme 7B) is favored by the authors. 

Kuca, K., Kassa, J. (2004). Oximes-induced reactivation of rat brain acetylcholinesterase inhibited by VX agent. Hum. Exp. Toxicol. 23 167-71. 

Clement, J.G. and Erhardt, N. In vitro oxime-induced reactivation of various molecular forms of soman-inhibited acetylcholinesterase in striated muscle from rat, monkey and human. Arch. Toxicol., 68, 648, 1994. 

Luo, C. et al. Aging and oxime-induced reactivation of nerve agent-inhibited human and guinea pig acet-ylchohnesterases, presented at the Bioscience Review, Maryland, USA, 2006a. 

Hanke, D.W. and Overton, M.A. 1991, Phosphylation kinetic constants and oxime-induced reactivation in acetylcholinesterase from fetal bovine serum, bovine caudate nucleus, and electric eel, J. Toxicol Environ. Health, vol. 34, no. 1, pp. 141-156. 

Jokanovic, M., Maksimovic, M., Kilibarda, V., Jovanovic, D., and Savic, D. Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates, Toxicol. Lett., 85,35-39, 1996. 

KINETICS OF OXIME-INDUCED REACTIVATION OF HUMAN ACHE IN VITRO... 

Luo C, Ashani Y and Doctor BP (1998a). Acceleration of oxime-induced reactivation of organophosphate -inhibited fetal bovine serum acetylcholinesterase by monoquaternary and bisquaternary ligands. Mol Pharmacol, 53, 718-726. 

B.P., and Taylor, R, Amino acid residues that control mono and bisquatemary oxime-induced reactivation of O-ethyl methylphosphonylated cholinesterase, in Enzymes of the Cholinesterase Eamily, Quinn, D.M., Balasubramanian, A.S., Doctor, B.P., and Taylor, P, Eds., Plenum Press, New York, 1975, 133. 

Maxwell, D.M., Lieske, C.N., and Brecht, K.M., Oxime-induced reactivation of carboxylesterase inhibited by organophosphoms compounds, Chem. Res. Toxicol., 7,428, 1994. 

Harris, I W Talbot, B, G., i-eniiox, W. J., and Anderson, D. R. (1989). The relationship between oxime-induced reactivation of citrbamylated aceiylcholiiiestera.se and antidotal efficacy against carbarttate intoxication. Toxicol. Appl. Pharmacol. 98, 128-133,... 

Luo, C., Ashani. Y., and Doctor, B. P. (1998). Acceleration of oxime-induced reactivation of organophtrspliatc-inhibited fetal bovine serum acetylcholinc,sterase by monoquatemary and bisquatemary ligands. Mol. Pharmacol. 53,718-726. 

There arc exceptions to the typical pesticidal OP structures described previously, and in the case of AChEs inhibited by these pesticides, less is known about reactivation rates, both spontaneous and oxime induced. These pesticides include EPN, leptophos, and cyanophenfos, which have one ethoxy and one phenyl group, and methamidophos, which is a methoxy. Wmethyl compound, Trichloronat, a phosphonate, has one ethoxy substituent and an ethyl group attached directly to the phosphorus atom. For some pesticides, it is not clear which group is... 

Delay in the treatment of OP poisoning produced by dimethoxy OPs may result in a significant proportion of the inhibited cholinestera.se undergoing the aging reaction and becoming refractory to oxime-induced reactivation. 

Langenbeig, J. P., DeJong. 1, P, A., Otto. M, F., and Benschop, H. P. (1988). Spontaneous and oxime induced reactivation of acctyl-choline.sterase inhibited by phosphoramidates. Arch. Toxicol. 62, 305-310. 

The Naito laboratory has investigated the applicability of radical reactions in solid-supported chemistry. A pronounced effect of the solid support on the stereochemical outcome of a radical reaction was reported for the addition of an alkyl radical onto the chiral oxime 139, delivering a-amino acid derivatives 140 in good yield and with high stereoselectivity (Scheme 6.32). Higher diastereoselectivities were observed with the substrate 139 immobilized on the solid support (>90% de), compared to comparable solution-phase reactions of 139 (72-85% de). This effect was rationalized based on the lower reactivity and reduced reaction rate of the immobilized oxime, inducing an enhanced selectivity. ... 

The abundance of diverse oximes as naturally occurring products is attributed, in general, to complicated metabolic processes that include enzyme-induced oxidation of either amino acids or biogenic amines, as well as to the relatively low reactivity of oximes compared to HA. The co-occurrence of HA and a variety of carbonyl-containing molecules in plants and animals may also contribute to the formation of the oxime bond in nature. 

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