Synthesis of DNA tagged Amides
Synthesis of DNA tagged Amides promoted by micellar catalysis and the judicious choice of linker molecule.
Unmet Need
Synthesis of DNA encoded libraries is a challenging process.
Using DNA tags means that the molecules are only soluble in water. They are not soluble in the organic solvents that support most organic synthesis.
Additionally, many organic transformations are incompatible with DNA. This leads to incomplete reaction and degradation of the DNA tag.
Current conditions for carrying out on-DNA amide chemistry use standard aqueous conditions. These conditions can lead to:
- incomplete reaction
- decomposition of DNA
- low substrate scope.
There are few options for screening conditions to address this because of the restriction to water soluble reagents. This means that libraries synthesised using this protocol will be suboptimal. They will not contain all the intended products and in some cases will contain DNA tags that code for the wrong molecule. This means they are far from ideal for drug screening.
The Technology
The technology is a method for carrying out on-DNA amide chemistry. The technology uses micelles to localise the coupling partners in an organic solvent environment whilst maintaining the DNA tag outside the micelle in an aqueous environment. The DNA tag and the coupling partner are linked via a carbon chain
Applications
- Synthesis DNA encoded Libraries for screening for new drug lead molecules
- Synthesis of oligonucleotide conjugates
Advantages
The technology leads to full reaction conversion (≥95%) with the DNA tag unaltered on amide compounds.
The technology gives syntheses of DEL amide libraries of much greater fidelity, which will give more robust screening results as well as containing more of the intended compounds. Moreover, the approach should be generally applicable - it potentially enables the application of a much wider range of chemistry, meaning far more diverse libraries can be synthesised (currently, a major limitation of standard methods).
Meet the team
Contact
- Tim Blackburn, Business Development Manager
- Tim.Blackburn@newcastle.ac.uk