Synthesis of 2'-O-modified adenosine building blocks and application for RNA interference

Dalibor Odadzic; Jesper B Bramsen; Romualdas Smicius; Claus Bus; Jørgen Kjems; Joachim W Engels

doi:10.1016/j.bmc.2007.09.019

Synthesis of 2'-O-modified adenosine building blocks and application for RNA interference

Dalibor Odadzic, Jesper B Bramsen, Romualdas Smicius, Claus Bus, Jørgen Kjems, Joachim W Engels

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

47 Citationer (Scopus)

Abstract

RNA-interference has been recognized as a powerful tool to control gene function and has been used for gene silencing by knocking down mRNA. Chemically modified RNAs, especially 2'-O-modification, successfully improved their physicochemical and pharmaceutical properties such as stability, nuclease resistance and delivery. Here, we report the synthesis of adenosine building blocks with different 2'-tethered modifications like aminoethyl and guanidinoethyl and show that they are compatible with RNAi function. They enhance the half life of the siRNA in serum suggesting that these modifications can enhance the pharmacokinetic properties and knock down activity of siRNAs in vivo.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry
Vol/bind	16
Nummer	1
Sider (fra-til)	518-529
Antal sider	12
ISSN	0968-0896
DOI	https://doi.org/10.1016/j.bmc.2007.09.019
Status	Udgivet - jan. 2008

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10.1016/j.bmc.2007.09.019

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abstract = "RNA-interference has been recognized as a powerful tool to control gene function and has been used for gene silencing by knocking down mRNA. Chemically modified RNAs, especially 2'-O-modification, successfully improved their physicochemical and pharmaceutical properties such as stability, nuclease resistance and delivery. Here, we report the synthesis of adenosine building blocks with different 2'-tethered modifications like aminoethyl and guanidinoethyl and show that they are compatible with RNAi function. They enhance the half life of the siRNA in serum suggesting that these modifications can enhance the pharmacokinetic properties and knock down activity of siRNAs in vivo.",

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author = "Dalibor Odadzic and Bramsen, {Jesper B} and Romualdas Smicius and Claus Bus and J{\o}rgen Kjems and Engels, {Joachim W}",

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AU - Odadzic, Dalibor

AU - Bramsen, Jesper B

AU - Smicius, Romualdas

AU - Bus, Claus

AU - Kjems, Jørgen

AU - Engels, Joachim W

PY - 2008/1

Y1 - 2008/1

N2 - RNA-interference has been recognized as a powerful tool to control gene function and has been used for gene silencing by knocking down mRNA. Chemically modified RNAs, especially 2'-O-modification, successfully improved their physicochemical and pharmaceutical properties such as stability, nuclease resistance and delivery. Here, we report the synthesis of adenosine building blocks with different 2'-tethered modifications like aminoethyl and guanidinoethyl and show that they are compatible with RNAi function. They enhance the half life of the siRNA in serum suggesting that these modifications can enhance the pharmacokinetic properties and knock down activity of siRNAs in vivo.

AB - RNA-interference has been recognized as a powerful tool to control gene function and has been used for gene silencing by knocking down mRNA. Chemically modified RNAs, especially 2'-O-modification, successfully improved their physicochemical and pharmaceutical properties such as stability, nuclease resistance and delivery. Here, we report the synthesis of adenosine building blocks with different 2'-tethered modifications like aminoethyl and guanidinoethyl and show that they are compatible with RNAi function. They enhance the half life of the siRNA in serum suggesting that these modifications can enhance the pharmacokinetic properties and knock down activity of siRNAs in vivo.

KW - Adenosine

KW - RNA Interference

KW - RNA Stability

KW - RNA, Small Interfering

U2 - 10.1016/j.bmc.2007.09.019

DO - 10.1016/j.bmc.2007.09.019

M3 - Journal article

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SP - 518

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JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 1

ER -

Synthesis of 2'-O-modified adenosine building blocks and application for RNA interference

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