Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro
Identifieur interne : 005F09 ( Main/Merge ); précédent : 005F08; suivant : 005F10Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro
Auteurs : Rajendra P. Jain [Canada] ; Hanna I. Pettersson ; JIANMIN ZHANG ; Katherine D. Aull ; Pascal D. Fortin ; Carly Huitema ; Lindsay D. Eltis ; Jonathan C. Parrish ; Michael N. G. James ; David S. Wishart ; John C. VederasSource :
- Journal of medicinal chemistry : (Print) [ 0022-2623 ] ; 2004.
Descripteurs français
- Pascal (Inist)
- Activité biologique, Antiviral, Virus syndrome respiratoire aigu sévère, Syndrome respiratoire aigu sévère, Inhibiteur protease, Inhibiteur enzyme, Peptidases, In vitro, Modélisation, Modèle moléculaire, Synthèse chimique, Peptide, Tétrapeptide, Aminocétone, Phtalazine dérivé, Valine dérivé, Thréonine dérivé, Glutamine analogue.
English descriptors
- KwdEn :
Abstract
The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at the α-position were synthesized and tested as reversible inhibitiors against SARS 3CLpro. Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based "warheads" generated significantly better inhibitors (4a-c, 8a-d) with IC50 values ranging from 0.60 to 70 μM.
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Pascal:05-0097618Le document en format XML
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<term>Biological activity</term>
<term>Chemical synthesis</term>
<term>Enzyme inhibitor</term>
<term>In vitro</term>
<term>Modeling</term>
<term>Molecular model</term>
<term>Peptidases</term>
<term>Peptides</term>
<term>Phthalazine derivatives</term>
<term>Protease inhibitor</term>
<term>Severe acute respiratory syndrome</term>
<term>Severe acute respiratory syndrome virus</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Activité biologique</term>
<term>Antiviral</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Inhibiteur protease</term>
<term>Inhibiteur enzyme</term>
<term>Peptidases</term>
<term>In vitro</term>
<term>Modélisation</term>
<term>Modèle moléculaire</term>
<term>Synthèse chimique</term>
<term>Peptide</term>
<term>Tétrapeptide</term>
<term>Aminocétone</term>
<term>Phtalazine dérivé</term>
<term>Valine dérivé</term>
<term>Thréonine dérivé</term>
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<front><div type="abstract" xml:lang="en">The 3C-like proteinase (3CL<sup>pro</sup>
) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at the α-position were synthesized and tested as reversible inhibitiors against SARS 3CL<sup>pro</sup>
. Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based "warheads" generated significantly better inhibitors (4a-c, 8a-d) with IC<sub>50</sub>
values ranging from 0.60 to 70 μM.</div>
</front>
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