SrasV1, Main, Curation, bibRecord, 005A58

Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro

Identifieur interne : 005A58 ( Main/Curation ); précédent : 005A57; suivant : 005A59

Synthesis 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. Vederas

Source :

Journal of medicinal chemistry : (Print) [ 0022-2623 ] ; 2004.

RBID : Pascal:05-0097618

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 :
- Aminoketone, Antiviral, Biological activity, Chemical synthesis, Enzyme inhibitor, In vitro, Modeling, Molecular model, Peptidases, Peptides, Phthalazine derivatives, Protease inhibitor, Severe acute respiratory syndrome, Severe acute respiratory syndrome virus, Tetrapeptide.

Abstract

The 3C-like proteinase (3CL^pro) 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^pro. 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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Le document en format XML

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<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>
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<term>Protease inhibitor</term>
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<term>Syndrome respiratoire aigu sévère</term>
<term>Inhibiteur protease</term>
<term>Inhibiteur enzyme</term>
<term>Peptidases</term>
<term>In vitro</term>
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<term>Modèle moléculaire</term>
<term>Synthèse chimique</term>
<term>Peptide</term>
<term>Tétrapeptide</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>
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Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro

Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri