About: Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays

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About: Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays
Creator	Schirmeister, Tanja Schiller, Markus Engels, Bernd Paasche, Alexander
Source	Medline; PMC
abstract	We investigated the reactions between substituted α,β‐unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS‐CoV M(pro)) by etacrynic acid derivatives as well as for the excess toxicity of substituted α,β‐unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4‐addition followed by a ketonization step, and underscores the importance of a base‐catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron‐pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s‐cis conformation leads to higher reactivity than the s‐trans conformation. The computed data explain the trends in measured inhibition potencies of substituted α,β‐unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease.
has issue date	2010-04-16(xsd:dateTime)
bibo:doi	10.1002/cmdc.201000020
bibo:pmid	20401893
has license	no-cc
sha1sum (hex)	a9efeab1a3e7cbc58c0bd69992602405f57acc48
schema:url	https://doi.org/10.1002/cmdc.201000020
resource representing a document's title	Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays
has PubMed Central identifier	PMC7162195
has PubMed identifier	20401893
schema:publication	ChemMedChem
resource representing a document's body	covid:a9efeab1a3e7cbc58c0bd69992602405f57acc48#body_text
is schema:about of	named entity 'Substrates' named entity 'Enzymes' named entity 'Computation' named entity 'Enzymes' named entity 'thiolate' named entity 'acrolein' named entity 'acrolein' named entity 'substituent' named entity 'rate constant' named entity 'thiophenol' named entity 'carbonyl compounds' named entity 'thiol' named entity 'direct addition' named entity 'phenyl' named entity 'PES' named entity 'thiol' named entity 'SARS' named entity 'etacrynic acid' named entity 'molecular structure' named entity 'polarizability' named entity 'trans' named entity 'direct addition' named entity 'double bond' named entity 'Informa' named entity 'alkyl' named entity 'hydrogen bonding' named entity 'olefin' named entity 'ketonization' named entity 'ammonia' named entity 'ketonization' named entity 'enolate' named entity 'ketones' named entity 'chlorine' named entity 'ppm' named entity 'carbonyl oxygen' named entity 'phenyl' named entity 'thiolate' named entity 'trans' named entity 'enolate' named entity 'deprotonation' named entity 'etacrynic acid' named entity 'aliphatic' named entity '1,4-addition' named entity 'enthalpic' named entity 'enol' named entity 'cis' named entity 'benzylic' named entity 'carbonyl' named entity 'base-catalyzed' named entity 'carbonyl' named entity 'dielectric constant' named entity 'ketonization' named entity 'enol form' named entity 'carboxylic acids' named entity 'cis' named entity 'Phenyl' named entity 'reactant' named entity 'enolate' named entity 'enolate' named entity 'intermolecular' named entity 'carbonyl' named entity 'quantum chemical' named entity 'electrophilic' named entity 'bicyclic' named entity 'stereospecific' named entity 'epoxides' named entity 'chemical assays' named entity 'thiol' named entity 'thiol' named entity 'irreversible inhibition' named entity 'proton' named entity '1,4-addition' named entity 'phenyl group' named entity 'electrophiles' named entity 'cation' named entity 'reaction path' named entity 'enzyme' named entity 'reactant'

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