Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/NIR-WEI-75ed5c39
Hi Nir @londonir
This looks like an interesting idea and I think that being able to easily achieve the transition state geometry will be key. The isoquinoline ring is electron-withdrawing and I’d expect this group to increase the intrinsic reactivity of the acrylamide (although not the extent of an additional carbonyl group). Another relevant factor is that both the isoquinoline nitrogen and the amide carbonyl oxygen accept hydrogen bonds from the protein which could lead to stabilization of a carbanionic transition state. The electron ‘pull’ of heterocycles can be modulated.
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