A convenient solid phase approach to obtain lipophilic 5′-phosphoramidate derivatives of DNA and RNA oligonucleotides

ABSTRACT

This paper explores the potential of a modified phosphotriester approach to the synthesis of 5′-phosphoramidate derivatives of DNA and RNA oligonucleotides. The modification of 5′-deprotected support-bound oligonucleotides is done in two steps: i) conversion of the 5′-OH group of an oligonucleotide into an activated phosphodiester, and ii) treatment of the activated phosphodiester with an aminocompound. The approach is efficient and compatible with conventional solid phase oligonucleotide synthesis. It can be used for the conjugation of therapeutically relevant oligonucleotides with functional moieties or carrier constructions, which are to be removed after endocytosis.

KEYWORDS:

• oligonucleotides
• DNA
• RNA
• phosphoramidate
• conjugate
• solid phase synthesis

Acknowledgements

The authors thank Marat F. Kassakin (Center of Mass Spectrometry Analysis ICBFM SB RAS) for the MS data, Dr. Mariya I. Meschaninova for the synthesis of rU₁₀, Dr. Alya G. Venyaminova, Dr. Maria A. Vorobjeva, Yuliya V. Sherstyuk (ICBFM SB RAS) for helpful discussions and proofreading of the manuscript. This work was supported by the RSF grant No. 16-15-10156.

Additional information

Funding

Russian Science Foundation [16-15-10156].