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Nucleosides and Oligonucleotides Incorporating 2-Thiothymine or 2-Thiouracil Derivatives as Modified Nucleobases

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Synthesis of Therapeutic Oligonucleotides

Abstract

Nucleosides containing 2-thiothymine and 2-thiouracil as base moieties have been incorporated into oligonucleotides to enhance their hybridization affinity and base discrimination ability. For the incorporation of these thio-bases into oligonucleotides, efficient methods for the synthesis of thio-modified nucleosides and the incorporation of the thio-nucleosides into oligonucleotides under solid-phase conditions are necessary. In this chapter, the physicochemical properties of thio-modified bases and the methods for the syntheses of 2-thiouridine and 2-thiothymidine are described. In addition, the solid-phase synthesis of oligonucleotides incorporating these thio-nucleosides is described.

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Abbreviations

Ura:

Uracil

s2Ura:

2-Thiouracil

Thy:

Thymine

s2Thy:

2-Thiothymine

U:

Uridine

s2U:

2-Thiouridine

T:

Thymidine

s2T:

2-Thiothymidine

rT:

Ribothymidine

rs2T:

2-Thioribothymidine

Bz:

Benzoyl

Tol:

Toluoyl

DMTr:

4,4′-dimethoxytrityl

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Author information

Authors and Affiliations

  1. Department of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan

    Kohji Seio

  2. Tokyo Institute of Technology, Yokohama, Kanagawa, Japan

    Mitsuo Sekine

Authors
  1. Kohji Seio
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  2. Mitsuo Sekine
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Corresponding author

Correspondence to Kohji Seio .

Editor information

Editors and Affiliations

  1. Osaka University, Suita, Osaka, Japan

    Satoshi Obika

  2. Tokyo Institute of Technology, Yokohama, Kanagawa, Japan

    Mitsuo Sekine

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Seio, K., Sekine, M. (2018). Nucleosides and Oligonucleotides Incorporating 2-Thiothymine or 2-Thiouracil Derivatives as Modified Nucleobases. In: Obika, S., Sekine, M. (eds) Synthesis of Therapeutic Oligonucleotides. Springer, Singapore. https://doi.org/10.1007/978-981-13-1912-9_7

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