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Article: Differential inhibitory activities and stabilisation of DNA aptamers against the SARS coronavirus helicase.

TitleDifferential inhibitory activities and stabilisation of DNA aptamers against the SARS coronavirus helicase.
Authors
Issue Date2008
Citation
Chembiochem : A European Journal Of Chemical Biology, 2008, v. 9 n. 18, p. 3037-3045 How to Cite?
AbstractThe helicase from severe acute respiratory syndrome coronavirus (SARS-CoV) possesses NTPase, duplex RNA/DNA-unwinding and RNA-capping activities that are essential for viral replication and proliferation. Here, we have isolated DNA aptamers against the SARS-CoV helicase from a combinatorial DNA library. These aptamers show two distinct classes of secondary structure, G-quadruplex and non-G-quadruplex, as shown by circular dichroism and gel electrophoresis. All of the aptamers that were selected stimulated ATPase activity of the SARS-CoV helicase with low-nanomolar apparent K(m) values. Intriguingly, only the non-G-quadruplex aptamers showed specific inhibition of helicase activities, whereas the G-quadruplex aptamers did not inhibit helicase activities. The non-G-quadruplex aptamer with the strongest inhibitory potency was modified at the 3'-end with biotin or inverted thymidine, and the modification increased its stability in serum, particularly for the inverted thymidine modification. Structural diversity in selection coupled to post-selection stabilisation has provided new insights into the aptamers that were selected for a helicase target. These aptamers are being further developed to inhibit SARS-CoV replication.
Persistent Identifierhttp://hdl.handle.net/10722/147596
ISSN
2015 SCImago Journal Rankings: 1.301
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShum, KTen_US
dc.contributor.authorTanner, JAen_US
dc.date.accessioned2012-05-29T06:04:50Z-
dc.date.available2012-05-29T06:04:50Z-
dc.date.issued2008en_US
dc.identifier.citationChembiochem : A European Journal Of Chemical Biology, 2008, v. 9 n. 18, p. 3037-3045en_US
dc.identifier.issn1439-7633en_US
dc.identifier.urihttp://hdl.handle.net/10722/147596-
dc.description.abstractThe helicase from severe acute respiratory syndrome coronavirus (SARS-CoV) possesses NTPase, duplex RNA/DNA-unwinding and RNA-capping activities that are essential for viral replication and proliferation. Here, we have isolated DNA aptamers against the SARS-CoV helicase from a combinatorial DNA library. These aptamers show two distinct classes of secondary structure, G-quadruplex and non-G-quadruplex, as shown by circular dichroism and gel electrophoresis. All of the aptamers that were selected stimulated ATPase activity of the SARS-CoV helicase with low-nanomolar apparent K(m) values. Intriguingly, only the non-G-quadruplex aptamers showed specific inhibition of helicase activities, whereas the G-quadruplex aptamers did not inhibit helicase activities. The non-G-quadruplex aptamer with the strongest inhibitory potency was modified at the 3'-end with biotin or inverted thymidine, and the modification increased its stability in serum, particularly for the inverted thymidine modification. Structural diversity in selection coupled to post-selection stabilisation has provided new insights into the aptamers that were selected for a helicase target. These aptamers are being further developed to inhibit SARS-CoV replication.en_US
dc.languageengen_US
dc.relation.ispartofChembiochem : a European journal of chemical biologyen_US
dc.subject.meshAptamers, Nucleotide - Chemistry - Pharmacologyen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshDna Helicases - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshG-Quadruplexesen_US
dc.subject.meshInhibitory Concentration 50en_US
dc.subject.meshKineticsen_US
dc.subject.meshSars Virus - Enzymologyen_US
dc.subject.meshViral Proteins - Antagonists & Inhibitors - Metabolismen_US
dc.titleDifferential inhibitory activities and stabilisation of DNA aptamers against the SARS coronavirus helicase.en_US
dc.typeArticleen_US
dc.identifier.emailTanner, JA:jatanner@hku.hken_US
dc.identifier.authorityTanner, JA=rp00495en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/cbic.200800491-
dc.identifier.pmid19031435-
dc.identifier.scopuseid_2-s2.0-59649092194en_US
dc.identifier.hkuros152816-
dc.identifier.volume9en_US
dc.identifier.issue18en_US
dc.identifier.spage3037en_US
dc.identifier.epage3045en_US
dc.identifier.eissn1439-7633-
dc.identifier.isiWOS:000261876900021-
dc.identifier.scopusauthoridShum, KT=20436474600en_US
dc.identifier.scopusauthoridTanner, JA=35513993000en_US

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