Properties of artificial cationic oligodiaminosaccharides and oligopeptides that bind to A-type oligonucleotide duplexes

Abstract

A critical strategy to improve the properties of oligonucleotide therapeutics is using cationic molecules as carriers. We developed artificial cationic molecules that bind to A-type oligonucleotide duplexes, such as siRNAs, in a stoichiometric ratio. In this study, we investigated the properties of oligo 2,6-diamino-D-galactoses (ODAGals) and L-2,4-diaminobutanoic acid oligomers (Dabs) and revealed their thermal and biological stabilization effects on A-type duplexes and their chemical stability. As a result, ODAGal and Dab with the same number of amino groups had the commensurate ability for the biological stabilization effect, whereas Dab enhanced the thermal stability of A-type duplexes more effectively than ODAGal.

Keywords:

• A-type oligonucleotide duplex
• cationic oligosaccharide
• cationic oligopeptide
• siRNA
• heteroduplex oligonucleotide

Acknowledgments

We thank Dr. Yayoi Yoshimura (Tokyo University of Science) for measuring the mass spectra. We thank Enago (www.enago.jp) for the English-language review.

Disclosure statement

The authors declare no conflicts of interest.

Author contributions

All authors conceptualized the research, T. S. conducted the experiments and wrote the manuscript, and K. S., R. I. H., and T. W. revised the manuscript. All authors analyzed data and approved the final version of the manuscript.

Data availability statement

The authors confirm that the data supporting the findings of this study are available in the article and/or its supplementary materials.

Additional information

Funding

This research was supported by the Science and Technology Platform Program for Advanced Biological Medicine (22am0401006s0104) from the Japan Agency for Medical Research and Development and JSPS KAKENHI (19K06993).