N(2)-Modified 2-aminopurine ribonucleosides as minor-groove-modulating adenosine replacements in duplex RNA - PubMed (original) (raw)

N(2)-Modified 2-aminopurine ribonucleosides as minor-groove-modulating adenosine replacements in duplex RNA

Hayden Peacock et al. Org Lett. 2010.

Abstract

Nucleoside analogs that project substituents into the minor groove when incorporated into duplex RNA perturb the binding of proteins and can affect base pairing specificity. The synthesis of 2-aminopurine ribonucleoside analogs and their phosphoramidites, their incorporation into duplex RNA, their postsynthetic modification via Cu-catalyzed azide-alkyne cycloaddition (CuAAC), and their effect on duplex stability and base pairing specificity are described.

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Figures

Figure 1

A Structure of an A–U base pair in duplex RNA, showing location of adenosine C2.18 B _N_2-Modified 2-aminopurines place steric bulk (R) in the duplex RNA minor groove.

Figure 2

Thermal denaturation (Tm) analysis of 12-mer RNA duplexes containing adenosine, 2-aminopurine, and _N_2-modified 2-aminopurine bases opposite the four common nucleobases.

Scheme 1

Preparation of _N_2-modified 2-aminopurine ribonucleosides via 2-fluoropurine intermediate.

Scheme 2

Preparation of _N_2-modified 2-aminopurine ribonucleosides via 2-bromopurine intermediate.

Scheme 3

Preparation of phosphoramidites.

Scheme 4

Post-synthetic RNA modification via CuAAC.

References

1. Maydanovych O, Easterwood LM, Cui T, Veliz EA, Pokharel S, Beal PA. Methods Enzymol. 2007;424:369–386. - PubMed
1. Suydam IT, Strobel SA. J. Am. Chem. Soc. 2008;130:13639–13648. - PMC - PubMed
1. Watts J, Deleavey G, Damha M. Drug Discov. Today. 2008;13:842–855. - PubMed
1. Terrazas M, Kool ET. Nucleic Acids Res. 2009;37:346–353. - PMC - PubMed
1. Rist MJ, Marino JP. Curr. Org. Chem. 2002;6:775–793.

N(2)-Modified 2-aminopurine ribonucleosides as minor-groove-modulating adenosine replacements in duplex RNA - PubMed (original) (raw)