Synthesis of water-soluble sequence-controlled polymers

Invention 2018-040

Synthesis of water-soluble sequence-controlled polymers

A versatile technique to introduce chemical functionality in nucleic acids and sequence-controlled polymers has been developed at McGill University.

Market Need

For biological polymers, nucleic acids and proteins use their primary sequence to structurally fold and recognize molecules in a seemingly limitless fashion. Using a number of different techniques, synthetic chemists are attempting to mimic these designs to produce structurally complex artificial oligomers and nanoparticles with protein-like structures. Unfortunately, synthetic polymers are not able to consistently replicate these biopolymer functions. With the proper chemical monomer backbone, however, sequence-controlled polymers could combine the sequence-driven flexibility of biologic polymers with the functional possibilities of synthetic oligomers.

Technology Summary

This invention is an efficient and scalable modification of the commonly used phosphoramidite synthesis method. With this technique it is simple to introduce many chemical functionalities, such as amino acids and sugars, to nucleic acids and sequence-controlled oligomers. Based on the integration of specific amine bases as the monomer backbone using automated DNA synthesis, this strategy provides an efficient method of creating synthetic polymers that mimic biological function. Furthermore, these water-soluble oligomers with sequence controlled functional groups can be synthesized in yields greater than 90% in almost all cases. As the cost of phosphoramidite synthesis continues to decline, this process will significantly expand the library of available functionalities for nucleic acid and sequence-controlled polymers.

Advantages

• Attachment yields were greater than 90% for attaching different chemical monomers to nucleic acids and artificial oligophosphodiesters
• Readily available amines or azides can be modified into the necessary phosphoramidites in only two steps

Patent Status

Filed PCT