Synthetic oligonucleotides as RNA mimetics: 2′-modified RNAs and N3′→P5′ phosphoramidates
Identifieur interne : 003690 ( Main/Exploration ); précédent : 003689; suivant : 003691Synthetic oligonucleotides as RNA mimetics: 2′-modified RNAs and N3′→P5′ phosphoramidates
Auteurs : M. Egli [États-Unis] ; S. M. Gryaznov [États-Unis]Source :
- Cellular and Molecular Life Sciences CMLS [ 1420-682X ] ; 2000-09-01.
English descriptors
Abstract
Abstract.: Significant interest in synthetic DNA and RNA oligonucleotides and their analogues has marked the past two decades of research in chemistry and biochemistry. This attention was largely determined by the great potential of these compounds for various therapeutic applications such as antisense, antigene and ribozyme-based agents. Modified oligonucleotides have also become powerful molecular biological and biochemical research tools that allow fast and efficient regulation of gene expression and gene functions in vitro and in vivo. These applications in turn are based on the ability of the oligonucleotides to form highly sequence-specific complexes with nucleic acid targets of interest. This review summarizes recent advances in the design, synthesis, biochemical and structural properties of various RNA analogues. These comprise 3′-modified oligonucleotide N3′→P5′ phosphoramidates, analogues with modifications at the 2′-position of nucleoside sugar rings, or combinations of the two. Among the properties of the RNA minetics reviewed here are the thermal stability of their duplexes and triplexes, hydrolytic resistance to cellular nucleases and biological activity in in vitro and in vivo systems. In addition, key structural aspects of the complexes formed by the RNA analogues, including interaction with water molecules and ions, are analyzed and presented.
Url:
DOI: 10.1007/PL00000628
Affiliations:
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Egli</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Pharmacology and Biological Chemistry and The Drug Discovery Program, Northwestern University Medical School, Chicago (Illinois 60611, USA)</wicri:regionArea><wicri:noRegion>USA)</wicri:noRegion></affiliation></author><author><name sortKey="Gryaznov, S M" sort="Gryaznov, S M" uniqKey="Gryaznov S" first="S. M." last="Gryaznov">S. M. Gryaznov</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geron Corporation, Nucleic Acids Chemistry, 230 Constitution Drive, Menlo Park (California 94025, USA), Fax +1 650 473 7750, e-mail: sgryaznov@geron.com</wicri:regionArea><wicri:noRegion>e-mail: sgryaznov@geron.com</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Cellular and Molecular Life Sciences CMLS</title><title level="j" type="abbrev">CMLS, Cell. Mol. Life Sci.</title><idno type="ISSN">1420-682X</idno><idno type="eISSN">1420-9071</idno><imprint><publisher>Birkhäuser Verlag</publisher><pubPlace>Basel</pubPlace><date type="published" when="2000-09-01">2000-09-01</date><biblScope unit="volume">57</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1440">1440</biblScope><biblScope unit="page" to="1456">1456</biblScope></imprint><idno type="ISSN">1420-682X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1420-682X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Key words. RNA mimetic; oligonucleotide N3′→P5′ phosphoramidate; sugar-base modification; structure; thermal stability.</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract.: Significant interest in synthetic DNA and RNA oligonucleotides and their analogues has marked the past two decades of research in chemistry and biochemistry. This attention was largely determined by the great potential of these compounds for various therapeutic applications such as antisense, antigene and ribozyme-based agents. Modified oligonucleotides have also become powerful molecular biological and biochemical research tools that allow fast and efficient regulation of gene expression and gene functions in vitro and in vivo. These applications in turn are based on the ability of the oligonucleotides to form highly sequence-specific complexes with nucleic acid targets of interest. This review summarizes recent advances in the design, synthesis, biochemical and structural properties of various RNA analogues. These comprise 3′-modified oligonucleotide N3′→P5′ phosphoramidates, analogues with modifications at the 2′-position of nucleoside sugar rings, or combinations of the two. Among the properties of the RNA minetics reviewed here are the thermal stability of their duplexes and triplexes, hydrolytic resistance to cellular nucleases and biological activity in in vitro and in vivo systems. In addition, key structural aspects of the complexes formed by the RNA analogues, including interaction with water molecules and ions, are analyzed and presented.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Egli, M" sort="Egli, M" uniqKey="Egli M" first="M." last="Egli">M. Egli</name></noRegion><name sortKey="Gryaznov, S M" sort="Gryaznov, S M" uniqKey="Gryaznov S" first="S. M." last="Gryaznov">S. M. Gryaznov</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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