How to implement PDA Linker.

[davidsaeb]

Hi Jérôme,

I am unclear on how to use the phosphoramidate bond linker for MNA. Currently, MNA nucleosides are configured to use dna_phosphate.json as the linker in the library.py. Given that the paper focuses on using a methylaminophosphoroamidate linker and that chemistry is described in the tutorial, I am confused on how to use it in Ducque. I am not currently seeing a phosphoroamidate linker in library.py.

Any guidance would be appreciated.

Thanks!

[jrihon]

Hiya David,

The way ducque builds is by consecutively using a nucleoside fragment, then a linker, then a nucleoside again etc.

Since the nucleoside fragment of the morpholino ring ends with the N3' nitrogen atom, and the phosphate linker starts with the P phosphorous atom, I did not have to bother creating a specific phosphoroamidate linker. I could just reuse the phosphate fragment with the morpholino and call it a day.

Also, the paper does not focus on methylaminophosphoroamidate. Just regular -N3'-PO2-O6'- , no methyls involved.
If you need that particular linker, you can build it into the library yourself following the documentation.

Hope this helps and if anything arises let me know.

Cheers

[jrihon]

I highly suggest you reach out to my previous lab. In particular my former PI eveline.lescrinier@kuleuven.be

And especially one of her students that has continued the work and characterisation of morpholino derivates (most likely the methyl variant we've already done) : sten.reynders@kuleuven.be