SrasV1, Main, Merge, bibRecord, 003610

Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant

Identifieur interne : 003610 ( Main/Merge ); précédent : 003609; suivant : 003611

Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant

Auteurs : Kenichi Akaji [Japon] ; Hiroyuki Konno [Japon] ; Mari Onozuka [Japon] ; Ayumi Makino [Japon] ; Hiroyuki Saito [Japon] ; Kazuto Nosaka [Japon]

Source :

Bioorganic & medicinal chemistry [ 0968-0896 ] ; 2008.

RBID : Pascal:09-0041831

Descripteurs français

Pascal (Inist)
- Peptide, Aldéhyde, Inhibiteur protease, Mutation, Cysteine endopeptidases, Virus syndrome respiratoire aigu sévère, Résistance hydrolyse, Activité biologique, Synthèse chimique, Synthèse peptidique, In vitro, Inhibiteur enzyme, Glutamique acide(acétylthréonyl-séryl-alanyl-valyl-leucyl-1-désoxy).

English descriptors

KwdEn :
- Aldehyde, Biological activity, Chemical synthesis, Cysteine endopeptidases, Enzyme inhibitor, Hydrolysis resistance, In vitro, Mutation, Peptide synthesis, Peptides, Protease inhibitor, Severe acute respiratory syndrome virus.

Abstract

The 3C-like (3CL) protease of the severe acute respiratory syndrome (SARS) coronavirus is a key enzyme for the virus maturation. We found for the first time that the mature SARS 3CL protease is subject to degradation at 188Arg/189Gln. Replacing Arg with lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a K_m of 33.8 μM and k_cat of 4753 s^-1. Compared with the value reported for the mature protease containing a C-terminal His-tag, the relative activity of the mutant was nearly 10⁶. Novel peptide-aldehyde derivatives containing a side-chain-protected C-terminal Gln efficiently inhibited the catalytic activity of the R188I mutant. The results indicated for the first time that the tetrapeptide sequence is enough for inhibitory activities of peptide-aldehyde derivatives.

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Le document en format XML

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<author><name sortKey="Onozuka, Mari" sort="Onozuka, Mari" uniqKey="Onozuka M" first="Mari" last="Onozuka">Mari Onozuka</name>
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<term>Enzyme inhibitor</term>
<term>Hydrolysis resistance</term>
<term>In vitro</term>
<term>Mutation</term>
<term>Peptide synthesis</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Peptide</term>
<term>Aldéhyde</term>
<term>Inhibiteur protease</term>
<term>Mutation</term>
<term>Cysteine endopeptidases</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Résistance hydrolyse</term>
<term>Activité biologique</term>
<term>Synthèse chimique</term>
<term>Synthèse peptidique</term>
<term>In vitro</term>
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<front><div type="abstract" xml:lang="en">The 3C-like (3CL) protease of the severe acute respiratory syndrome (SARS) coronavirus is a key enzyme for the virus maturation. We found for the first time that the mature SARS 3CL protease is subject to degradation at 188Arg/189Gln. Replacing Arg with lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a K<sub>m</sub>
 of 33.8 μM and k<sub>cat</sub>
 of 4753 s<sup>-1</sup>
. Compared with the value reported for the mature protease containing a C-terminal His-tag, the relative activity of the mutant was nearly 10<sup>6</sup>
. Novel peptide-aldehyde derivatives containing a side-chain-protected C-terminal Gln efficiently inhibited the catalytic activity of the R188I mutant. The results indicated for the first time that the tetrapeptide sequence is enough for inhibitory activities of peptide-aldehyde derivatives.</div>
</front>
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<name sortKey="Konno, Hiroyuki" sort="Konno, Hiroyuki" uniqKey="Konno H" first="Hiroyuki" last="Konno">Hiroyuki Konno</name>
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Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant

Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant

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Descripteurs français

English descriptors

Abstract

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