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Toxicology Research Vol -4

Toxicology Research Vol -3

Toxicology Research Vol -2

Toxicology Research Vol -1

Mechanistic understanding of molecular initiating events (MIEs) using NMR spectroscopy

Content Provider	Royal Society of Chemistry (RSC)
Author	Simpson, Wendy Gutsell, Stephen Cubberley, Richard Aleksic, Maja Russell, Paul J. Sanderson, Paul N.
Copyright Year	2016
Abstract	Toxicological risk assessments in the 21st century are increasingly being driven by the Adverse Outcome Pathways (AOP) conceptual framework in which the Molecular Initiating Event (MIE) is of fundamental importance to pathway progression. For those MIEs that involve covalent chemical reactions, such as protein haptenation, determination of relative rates and mechanisms of reactions is a prerequisite for their understanding. The utility of NMR spectroscopy as an experimental technique for effectively providing reaction rate and mechanistic information for early assessment of likely MIE(s) has been demonstrated. To demonstrate the concept, model systems exemplifying common chemical reactions involved in the covalent modification of proteins were utilized; these involved chemical reactions of electrophilic species (representing different mechanistic classes) with simple amine and thiol nucleophiles acting as surrogates for the reactive groups of lysine and cysteine protein side chains respectively. Such molecular interactions are recognized as critical mechanisms in a variety of chemical and drug toxicities, including respiratory and skin sensitization and liver toxicity as well as being the key mechanism of action for a number of therapeutic agents.
Starting Page	34
Ending Page	44
Page Count	11
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	5
Issue Number	1
Journal	Toxicology Research
DOI	10.1039/c5tx00246j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	AOP Thiol Cysteine Lysine Liver Covalent bond Nuclear magnetic resonance spectroscopy Reaction rate Protein Electrophile
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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