Internal Reference: 2018-040
Market Need
The precise synthesis of sequence-controlled polymers, particularly modified oligonucleotides, is crucial for diverse applications ranging from drug discovery to nanotechnology. Automated solid-phase phosphoramidite chemistry is the established method but existing non-nucleosidic modifications still face significant challenges. These can be the introduction of chirality, often leading to mixtures of diastereoisomers that complicate purification and result in inconsistent biological activity, which is problematic for regulatory approval. Furthermore, many current monomers lack the necessary chemical stability to withstand the rigorous conditions of solid-phase synthesis, as well as being complex, costly, or relying on racemic starting materials, limiting their widespread utility and the overall chemical diversity achievable in sequence-controlled polymers.
Technology Overview
This invention provides an achiral, non-nucleosidic phosphoramidite monomer featuring a tertiary amine backbone which prevents intramolecular degradation and ensures high stability and efficient coupling during automated solid-phase synthesis. It is a fast and cost-efficient synthesis of reagents used to modify synthetic DNA and RNA strands and it allows the introduction of a variety of functional moieties, including fluorescent dyes, biotin, or chemical handles that can be further functionalized through click-chemistry. The location and number of modifications on one nucleic acid strand can be tuned at will.
Commercial Advantages
- Straight-forward synthesis and simple design allow to reduce costs on DNA modification.
- Obtention of highly functionalized strands with outstanding yields and purity.
- Only one isomer is produced, whichever the number of modifications.
- Useful for any applications related to nucleic acid chemistry (sequencing, gene silencing, aptamers, fluorescence assays, PCR primers…)
- Already used in DNA nanotechnology, fluorescent assays with cells, DNAzymes and aptamers.
Additional Information
- Researcher: Hanadi Sleiman
- Patents: United States: US 17/263,243 (Granted); Canada: CA 3,108,806 (Filed)
- Publications of work:
- -J Org Chem. 2018, 83 (17): 9774-9786.
- -Angew. Chemie Int. Ed. 2019, 58 (10), 3042–3047
- -ACS Cent. Sci. 2019, 5, 5, 882-891
- -Angew. Chem. Int. Ed. 2020, 59, 3573;
- Keywords: Platform, Research Tool, Synthesis Methods
