| Structural highlights
Function
[ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.[1] [2] [3] [4]
Publication Abstract from PubMed
The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLo-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLo-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLo-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.
Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate.,Hsu FL, Bae SY, McGuire J, Anderson DR, Bester SM, Height JJ, Pegan SD, Walz AJ ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi:, 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9. PMID:31097996[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chhajlani V, Derr D, Earles B, Schmell E, August T. Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase. FEBS Lett. 1989 Apr 24;247(2):279-82. PMID:2714437
- ↑ Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A. The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. J Biol Chem. 1991 Dec 15;266(35):23977-84. PMID:1748670
- ↑ Shafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D, et al.. Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem. 1992 Sep 5;267(25):17640-8. PMID:1517212
- ↑ Yang L, He HY, Zhang XJ. Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neurosci Res. 2002 Apr;42(4):261-8. PMID:11985878
- ↑ Hsu FL, Bae SY, McGuire J, Anderson DR, Bester SM, Height JJ, Pegan SD, Walz AJ. Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate. ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi:, 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9. PMID:31097996 doi:http://dx.doi.org/10.1021/acsmedchemlett.9b00021
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