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Article: Synthesis and biophysical properties of arabinonucleic acids (ANA): Circular dichroic spectra, melting temperatures, and ribonuclease H susceptibility of ANA·RNA hybrid duplexes

TitleSynthesis and biophysical properties of arabinonucleic acids (ANA): Circular dichroic spectra, melting temperatures, and ribonuclease H susceptibility of ANA·RNA hybrid duplexes
Authors
Issue Date2000
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/biochemistry
Citation
Biochemistry, 2000, v. 39 n. 24, p. 7050-7062 How to Cite?
AbstractArabinonucleic acid (ANA), the 2'-epimer of RNA, was synthesized from arabinonucleoside building blocks by conventional solid-phase phosphoramidite synthesis. In addition, the biochemical and physicochemical properties of ANA strands of mixed base composition were evaluated for the first time. ANA exhibit certain characteristics desirable for use as antisense agents. They form duplexes with complementary RNA, direct RNase H degradation of target RNA molecules, and display resistance to 3'-exonucleases. Since RNA does not elicit RNase H activity, our findings establish that the stereochemistry at C2' (ANA versus RNA) is a key determinant in the activation of the enzyme RNase H. Inversion of stereochemistry at C2' is most likely accompanied by a conformational change in the furanose sugar pucker from C3'-endo (RNA) to C2'-endo ('DNA-like') pucker (ANA) [Noronha and Damha (1998) Nucleic Acids Res. 26, 2665-2671; Venkateswarlu and Ferguson (1999) J. Am. Chem. Soc. 121, 5609-5610]. This produces ANA/RNA hybrids whose CD spectra (i.e., helical conformation) are more similar to the native DNA/RNA substrates than to those of the pure RNA/RNA duplex. These features, combined with the fact that ara- 2'OH groups project into the major groove of the helix (where they should not interfere with RNase H binding), help to explain the RNase H activity of ANA/RNA hybrids.
Persistent Identifierhttp://hdl.handle.net/10722/167663
ISSN
2015 Impact Factor: 2.876
2015 SCImago Journal Rankings: 1.769
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNoronha, AMen_US
dc.contributor.authorWilds, CJen_US
dc.contributor.authorLok, CNen_US
dc.contributor.authorViazovkina, Ken_US
dc.contributor.authorArion, Den_US
dc.contributor.authorParniak, MAen_US
dc.contributor.authorDamha, MJen_US
dc.date.accessioned2012-10-08T03:09:35Z-
dc.date.available2012-10-08T03:09:35Z-
dc.date.issued2000en_US
dc.identifier.citationBiochemistry, 2000, v. 39 n. 24, p. 7050-7062en_US
dc.identifier.issn0006-2960en_US
dc.identifier.urihttp://hdl.handle.net/10722/167663-
dc.description.abstractArabinonucleic acid (ANA), the 2'-epimer of RNA, was synthesized from arabinonucleoside building blocks by conventional solid-phase phosphoramidite synthesis. In addition, the biochemical and physicochemical properties of ANA strands of mixed base composition were evaluated for the first time. ANA exhibit certain characteristics desirable for use as antisense agents. They form duplexes with complementary RNA, direct RNase H degradation of target RNA molecules, and display resistance to 3'-exonucleases. Since RNA does not elicit RNase H activity, our findings establish that the stereochemistry at C2' (ANA versus RNA) is a key determinant in the activation of the enzyme RNase H. Inversion of stereochemistry at C2' is most likely accompanied by a conformational change in the furanose sugar pucker from C3'-endo (RNA) to C2'-endo ('DNA-like') pucker (ANA) [Noronha and Damha (1998) Nucleic Acids Res. 26, 2665-2671; Venkateswarlu and Ferguson (1999) J. Am. Chem. Soc. 121, 5609-5610]. This produces ANA/RNA hybrids whose CD spectra (i.e., helical conformation) are more similar to the native DNA/RNA substrates than to those of the pure RNA/RNA duplex. These features, combined with the fact that ara- 2'OH groups project into the major groove of the helix (where they should not interfere with RNase H binding), help to explain the RNase H activity of ANA/RNA hybrids.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/biochemistryen_US
dc.relation.ispartofBiochemistryen_US
dc.subject.meshArabinonucleosides - Chemistryen_US
dc.subject.meshCircular Dichroismen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshNucleic Acid Conformationen_US
dc.subject.meshNucleic Acid Denaturationen_US
dc.subject.meshNucleic Acid Heteroduplexes - Chemistryen_US
dc.subject.meshNucleic Acid Hybridizationen_US
dc.subject.meshPhosphodiesterase Ien_US
dc.subject.meshPhosphoric Diester Hydrolases - Chemistryen_US
dc.subject.meshRna - Chemistryen_US
dc.subject.meshRibonuclease H - Metabolismen_US
dc.subject.meshTemperatureen_US
dc.titleSynthesis and biophysical properties of arabinonucleic acids (ANA): Circular dichroic spectra, melting temperatures, and ribonuclease H susceptibility of ANA·RNA hybrid duplexesen_US
dc.typeArticleen_US
dc.identifier.emailLok, CN:cnlok@hku.hken_US
dc.identifier.authorityLok, CN=rp00752en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/bi000280ven_US
dc.identifier.pmid10852702-
dc.identifier.scopuseid_2-s2.0-0034691285en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034691285&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume39en_US
dc.identifier.issue24en_US
dc.identifier.spage7050en_US
dc.identifier.epage7062en_US
dc.identifier.isiWOS:000087778300003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridNoronha, AM=7006073110en_US
dc.identifier.scopusauthoridWilds, CJ=6701808160en_US
dc.identifier.scopusauthoridLok, CN=7006410829en_US
dc.identifier.scopusauthoridViazovkina, K=7801509019en_US
dc.identifier.scopusauthoridArion, D=6603734480en_US
dc.identifier.scopusauthoridParniak, MA=7006356357en_US
dc.identifier.scopusauthoridDamha, MJ=7007107329en_US

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