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Oligonucleotide analogues containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond

Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

A dinucleotide containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond was synthesized by the interaction of 3′-deoxy-3′-amino-5′-O-(tert-butyldimethylsilyl)thymidine with 3′-O-benzyl-2′-O-tert-butyldimethylsilyl-5′-deoxy-5′-carboxymethylribosylthymine, which was obtained from 2′-O-acetyl-3′-O-benzyl-5′-deoxy-5′-ethoxycarbonylmethylribosylthymine through the methanolysis of the acetyl group followed by silylation of liberated hydroxyl and ester saponification. After standard manipulation with protecting groups, the dinucleotide was converted into 3′-O(2-cyanoethyl-N,N-diisopropylphosphoramidite), which was used for the synthesis of modified oligonucleotides on an automated synthesizer. The melting curves of the duplexes formed by modified and complementary natural oligonucleotides were registered, and the melting temperatures and thermodynamic parameters of the duplex formation were calculated. The introduction of a single modified bond into the oligonucleotide led to an insignificant decrease in the melting temperature of these duplexes as compared to unmodified ones.

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Abbreviations

Bn:

benzyl

DIPEA:

diisopropylethylamine

TBDMS-Cl:

tert-butyldimethylsilyl chloride

TEAA:

triethylammonium acetate

(MeO)2Tr:

dimethoxytrityl

TFA:

trifluoroacetic acid

THF:

tetrahydrofuran

TBAF:

tetrabutylammonium fluoride

cT:

5′-deoxy-5′-carboxymethyl-5′-ribosylthymine

Ta:

3′-amino-3′-deoxythymidine

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Correspondence to V. L. Florent’ev.

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Original Russian Text © A.M. Varizhuk, S.V. Kochetkova, N.A. Kolganova, E.N. Timofeev, V.L. Florent’ev, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 2, pp. 215–222.

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Varizhuk, A.M., Kochetkova, S.V., Kolganova, N.A. et al. Oligonucleotide analogues containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond. Russ J Bioorg Chem 36, 199–206 (2010). https://doi.org/10.1134/S1068162010020093

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  • DOI: https://doi.org/10.1134/S1068162010020093

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