Prediction of a new broad-spectrum reactivator capable of reactivating acetylcholinesterase inhibited by nerve agents

Abstract Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents—GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme ‘cocktail’ comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.

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A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents

10.1101/748749 ◽

2019 ◽

Author(s):

Dragana Despotovic ◽

Einav Aharon ◽

Artem Dubovetskyi ◽

Haim Leader ◽

Yacov Ashani ◽

...

Keyword(s):

Broad Spectrum ◽

Entire Range ◽

Nerve Agents ◽

Ester Bond ◽

Minimal Impact ◽

Entire Spectrum ◽

Enzyme Cocktail ◽

Enzymatic Detoxification ◽

Single Enzyme

AbstractNerve agents are organophosphates that potently inhibit acetylcholinesterase and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity, and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents – GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX, and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme ‘cocktail’ comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.

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A Strengths-Based Approach to Autism: Neurodiversity and Partnering With the Autism Community

Perspectives of the ASHA Special Interest Groups ◽

10.1044/persp2.sig1.56 ◽

2017 ◽

Vol 2 (1) ◽

pp. 56-68 ◽

Cited By ~ 8

Author(s):

Amy L. Donaldson ◽

Karen Krejcha ◽

Andy McMillin

Keyword(s):

Broad Spectrum ◽

First Language ◽

Family Members ◽

Community Identity ◽

Speech Language Pathologists

The autism community represents a broad spectrum of individuals, including those experiencing autism, their parents and/or caregivers, friends and family members, professionals serving these individuals, and other allies and advocates. Beliefs, experiences, and values across the community can be quite varied. As such, it is important for the professionals serving the autism community to be well-informed about current discussions occurring within the community related to neurodiversity, a strengths-based approach to partnering with autism community, identity-first language, and concepts such as presumed competence. Given the frequency with which speech-language pathologists (SLPs) serve the autism community, the aim of this article is to introduce and briefly discuss these topics.

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