SrasV1, Main, Exploration, bibRecord, 002F45

Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase

Identifieur interne : 002F45 ( Main/Exploration ); précédent : 002F44; suivant : 002F46

Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase

Auteurs : Chaewoon Lee [Corée du Sud] ; JIN MOO LEE [Corée du Sud] ; Na-Ra Lee [Corée du Sud] ; Bong-Suk Jin [Corée du Sud] ; KYOUNG JIN JANG [Corée du Sud] ; Dong-Eun Kim [Corée du Sud] ; Yong-Joo Jeong [Corée du Sud] ; Youhoon Chong [Corée du Sud]

Source :

Bioorganic & medicinal chemistry letters : (Print) [ 0960-894X ] ; 2009.

RBID : Pascal:09-0237100

Descripteurs français

Pascal (Inist)
- Cétoacide, Dicétone, Inhibition, Duplex, DNA, Déroulement, Activité biologique, Virus syndrome respiratoire aigu sévère, Nucleoside-triphosphatase, Antiviral, In vitro, Synthèse chimique, Changement conformation, Nucleotidyltransferases, Helicases, But-2-énoïque acide(4-aryl-2-hydroxy-4-oxo).

English descriptors

KwdEn :
- Antiviral, Biological activity, Chemical synthesis, Conformational changes, DNA, Diketone, Duplex, In vitro, Inhibition, Ketoacid, Nucleoside-triphosphatase, Nucleotidyltransferases, Severe acute respiratory syndrome virus, Unwinding.

Abstract

As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn²⁺ ion binding sites in SCV Hel thereby disrupting and inhibiting both the NTPase and helicase activities. Phosphate release assay and FRET-based assay of the ADK analogues showed that the ADKs selectively inhibit the duplex DNA-unwinding activity without significant impact on the helicase ATPase activity. Also, antiviral activities of the ADKs were shown dependent upon the substituent. Taken together, these results suggest that there might be ADK-specific binding site in the SCV Hel, which warrants further investigations with diverse ADKs to provide valuable insights into rational design of specific SCV Hel inhibitors.

Affiliations:

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Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term>
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<term>DNA</term>
<term>Diketone</term>
<term>Duplex</term>
<term>In vitro</term>
<term>Inhibition</term>
<term>Ketoacid</term>
<term>Nucleoside-triphosphatase</term>
<term>Nucleotidyltransferases</term>
<term>Severe acute respiratory syndrome virus</term>
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<term>Inhibition</term>
<term>Duplex</term>
<term>DNA</term>
<term>Déroulement</term>
<term>Activité biologique</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Nucleoside-triphosphatase</term>
<term>Antiviral</term>
<term>In vitro</term>
<term>Synthèse chimique</term>
<term>Changement conformation</term>
<term>Nucleotidyltransferases</term>
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<front><div type="abstract" xml:lang="en">As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn<sup>2+</sup>
 ion binding sites in SCV Hel thereby disrupting and inhibiting both the NTPase and helicase activities. Phosphate release assay and FRET-based assay of the ADK analogues showed that the ADKs selectively inhibit the duplex DNA-unwinding activity without significant impact on the helicase ATPase activity. Also, antiviral activities of the ADKs were shown dependent upon the substituent. Taken together, these results suggest that there might be ADK-specific binding site in the SCV Hel, which warrants further investigations with diverse ADKs to provide valuable insights into rational design of specific SCV Hel inhibitors.</div>
</front>
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<name sortKey="Kyoung Jin Jang" sort="Kyoung Jin Jang" uniqKey="Kyoung Jin Jang" last="Kyoung Jin Jang">KYOUNG JIN JANG</name>
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Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase

Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase

Source :

Descripteurs français

English descriptors

Abstract

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

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri