Dear Francesco,
Thanks for that. From the discussion between you, I and your colleague Rodolfo we agree that a network expansion could take place and that a few people will have some overlapping interests and a good way forward is to establish collaborations with clear terms. I suggest a memorandum of understanding style where the uk-br network says what they intend to do and how both parties see how they can benefit and possibly making clear some exclusions upfront?
We (Diamond, OPPF, LSTH, Fiocruz) have to participate is this: We are interested in SmTGR as a system that can have new drug leads discovered using fragment based lead discovery but also in creating the pipeline and network of groups that can be used for lead discovery for other targets as well. My direct collaborators are Raymond Owens from the OPPF-UK, Nick Furnham from the LSTH (UK) and Floriano Silva (Fiocruz-Brasil) and we have an SmTGR construct (no Se-cys) which we used to do an xchem fragment screen (600 fragments) and are now preparing the first fragment hit series follow-up, growing from the fragments with the support from the OxXChem facility (Anthony Bradley and F von Delft-UK). We also have phenotypic assay and chemistry collaborators for later series developments (Brasil). Apart from TGR, the UK-BR team is interested in creating a platform/network to enable other (neglected disease) targets to go through the same process through the network. We currently have a small grant to fund ~150 follow up fragments to: do crystallography with the hit follow ups and assess binding in vitro. This is to happen between June and December (1 person, 3 months effort).
An example collaboration with the IT-US network and develop an active follow-up informed by the fragment screening.
Another example of mutual benefit would be to perform fragment screening on the Sec construct. You asked about the electrophiles. We have a library of covalent compounds from a London group that could be used, for instance. What do you have in mind regarding the electrophiles?
