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Investigation of Lysine-Functionalized Dendrimers as Dichlorvos Detoxification Agents

Author:
Durán-Lara, Esteban F., Marple, Jennifer L., Giesen, Joseph A., Fang, Yunlan, Jordan, Jacobs H., Godbey, W Terrence, Marican, Adolfo, Santos, Leonardo S., Grayson, Scott M.
Source:
Biomacromolecules 2015 v.16 no.11 pp. 3434-3444
ISSN:
1526-4602
Subject:
acetylcholinesterase, amines, antidotes, chemical elements, dichlorvos, gene transfer, heavy metals, lysine, pH, poisoning, polyesters, toxicity, toxins
Abstract:
Lysine-containing polymers have seen broad application due to their amines’ inherent ability to bind to a range of biologically relevant molecules. The synthesis of multiple generations of polyester dendrimers bearing lysine groups on their periphery is described in this report. Their hydrolytic stabilities with respect to pH and time, their toxicity to a range of cell lines, and their possible application as nano-detoxification agents of organophosphate compounds are all investigated. These zeroth-, first-, and second-generation water-soluble dendrimers have been designed to bear exactly 4, 8, and 16 lysine groups, respectively, on their dendritic periphery. Such monodisperse bioactive polymers show potential for a range of applications including drug delivery, gene delivery, heavy metal binding, and the sequestration of organic toxins. These monodisperse bioactive dendrimers were synthesized using an aliphatic ester dendritic core (prepared from pentaerythritol) and protected amino acid moieties. This library of lysine-conjugated dendrimers showed the ability to efficiently capture the pesticide dichlorvos, confirming the potential of dendrimer-based antidotes to maintain acetylcholinesterase activity in response to poisoning events.
Agid:
5333682