Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase.
Identifieur interne : 002B77 ( Main/Exploration ); précédent : 002B76; suivant : 002B78Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase.
Auteurs : Chaewoon Lee [Corée du Sud] ; Jin Moo Lee ; Na-Ra Lee ; Bong-Suk Jin ; Kyoung Jin Jang ; Dong-Eun Kim ; Yong-Joo Jeong ; Youhoon ChongSource :
- Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2009.
Descripteurs français
- KwdFr :
- ADN (), Chimie pharmaceutique (), Concentration inhibitrice 50, Conception de médicament, Cétoacides (), Helicase (), Ions, Modèles chimiques, Nucleoside-triphosphatase (), Phosphates (), Relation structure-activité, Sites de fixation, Transfert d'énergie par résonance de fluorescence, Virus du SRAS (enzymologie), Zinc ().
- MESH :
- enzymologie : Virus du SRAS.
- ADN, Chimie pharmaceutique, Concentration inhibitrice 50, Conception de médicament, Cétoacides, Helicase, Ions, Modèles chimiques, Nucleoside-triphosphatase, Phosphates, Relation structure-activité, Sites de fixation, Transfert d'énergie par résonance de fluorescence, Zinc.
English descriptors
- KwdEn :
- Binding Sites, Chemistry, Pharmaceutical (methods), DNA (chemistry), DNA Helicases (chemistry), Drug Design, Fluorescence Resonance Energy Transfer, Inhibitory Concentration 50, Ions, Keto Acids (chemistry), Models, Chemical, Nucleoside-Triphosphatase (chemistry), Phosphates (chemistry), SARS Virus (enzymology), Structure-Activity Relationship, Zinc (chemistry).
- MESH :
- chemical , chemistry : DNA, DNA Helicases, Keto Acids, Nucleoside-Triphosphatase, Phosphates, Zinc.
- enzymology : SARS Virus.
- methods : Chemistry, Pharmaceutical.
- Binding Sites, Drug Design, Fluorescence Resonance Energy Transfer, Inhibitory Concentration 50, Ions, Models, Chemical, Structure-Activity Relationship.
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 Zn(2+) 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.
DOI: 10.1016/j.bmcl.2009.02.010
PubMed: 19233643
Affiliations:
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Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Lee, Jin Moo" sort="Lee, Jin Moo" uniqKey="Lee J" first="Jin Moo" last="Lee">Jin Moo Lee</name></author><author><name sortKey="Lee, Na Ra" sort="Lee, Na Ra" uniqKey="Lee N" first="Na-Ra" last="Lee">Na-Ra Lee</name></author><author><name sortKey="Jin, Bong Suk" sort="Jin, Bong Suk" uniqKey="Jin B" first="Bong-Suk" last="Jin">Bong-Suk Jin</name></author><author><name sortKey="Jang, Kyoung Jin" sort="Jang, Kyoung Jin" uniqKey="Jang K" first="Kyoung Jin" last="Jang">Kyoung Jin Jang</name></author><author><name sortKey="Kim, Dong Eun" sort="Kim, Dong Eun" uniqKey="Kim D" first="Dong-Eun" last="Kim">Dong-Eun Kim</name></author><author><name sortKey="Jeong, Yong Joo" sort="Jeong, Yong Joo" uniqKey="Jeong Y" first="Yong-Joo" last="Jeong">Yong-Joo Jeong</name></author><author><name sortKey="Chong, Youhoon" sort="Chong, Youhoon" uniqKey="Chong Y" first="Youhoon" last="Chong">Youhoon Chong</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry letters</title><idno type="eISSN">1464-3405</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites</term><term>Chemistry, Pharmaceutical (methods)</term><term>DNA (chemistry)</term><term>DNA Helicases (chemistry)</term><term>Drug Design</term><term>Fluorescence Resonance Energy Transfer</term><term>Inhibitory Concentration 50</term><term>Ions</term><term>Keto Acids (chemistry)</term><term>Models, Chemical</term><term>Nucleoside-Triphosphatase (chemistry)</term><term>Phosphates (chemistry)</term><term>SARS Virus (enzymology)</term><term>Structure-Activity Relationship</term><term>Zinc (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN ()</term><term>Chimie pharmaceutique ()</term><term>Concentration inhibitrice 50</term><term>Conception de médicament</term><term>Cétoacides ()</term><term>Helicase ()</term><term>Ions</term><term>Modèles chimiques</term><term>Nucleoside-triphosphatase ()</term><term>Phosphates ()</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Transfert d'énergie par résonance de fluorescence</term><term>Virus du SRAS (enzymologie)</term><term>Zinc ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>DNA</term><term>DNA Helicases</term><term>Keto Acids</term><term>Nucleoside-Triphosphatase</term><term>Phosphates</term><term>Zinc</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Chemistry, Pharmaceutical</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Drug Design</term><term>Fluorescence Resonance Energy Transfer</term><term>Inhibitory Concentration 50</term><term>Ions</term><term>Models, Chemical</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ADN</term><term>Chimie pharmaceutique</term><term>Concentration inhibitrice 50</term><term>Conception de médicament</term><term>Cétoacides</term><term>Helicase</term><term>Ions</term><term>Modèles chimiques</term><term>Nucleoside-triphosphatase</term><term>Phosphates</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Transfert d'énergie par résonance de fluorescence</term><term>Zinc</term></keywords></textClass></profileDesc></teiHeader><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(2+) 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></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><noCountry><name sortKey="Chong, Youhoon" sort="Chong, Youhoon" uniqKey="Chong Y" first="Youhoon" last="Chong">Youhoon Chong</name><name sortKey="Jang, Kyoung Jin" sort="Jang, Kyoung Jin" uniqKey="Jang K" first="Kyoung Jin" last="Jang">Kyoung Jin Jang</name><name sortKey="Jeong, Yong Joo" sort="Jeong, Yong Joo" uniqKey="Jeong Y" first="Yong-Joo" last="Jeong">Yong-Joo Jeong</name><name sortKey="Jin, Bong Suk" sort="Jin, Bong Suk" uniqKey="Jin B" first="Bong-Suk" last="Jin">Bong-Suk Jin</name><name sortKey="Kim, Dong Eun" sort="Kim, Dong Eun" uniqKey="Kim D" first="Dong-Eun" last="Kim">Dong-Eun Kim</name><name sortKey="Lee, Jin Moo" sort="Lee, Jin Moo" uniqKey="Lee J" first="Jin Moo" last="Lee">Jin Moo Lee</name><name sortKey="Lee, Na Ra" sort="Lee, Na Ra" uniqKey="Lee N" first="Na-Ra" last="Lee">Na-Ra Lee</name></noCountry><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Lee, Chaewoon" sort="Lee, Chaewoon" uniqKey="Lee C" first="Chaewoon" last="Lee">Chaewoon Lee</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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