Sunday, October 20, 2024

Streamlined proteome stability - find those drug on- /off- targets on 30 samples/day!

 


What a week for proteomic applications! 

This came up on great study I rambled about earlier this week, but drugs almost always target or affect proteins. Hopefully just the one you care about, but off-target effects can and do happen where that drug binds some other proteins.

PISA has been discussed on this blog before and you can probably find it in the search bar, but this and related applications expose a proteome to a drug and look at the proteome effects after treating the proteome at different temperatures prior to digestion.

If your drug is binding to a protein chances are that protein is going to fold/unfold at different temperatures and alter the downstream peptides you quantify. Super cool stuff, right?!? 

The problem with just about every earlier study is that it takes freaking forever. Remember that to get a decent coverage of the proteome even 5 years ago could take 1 day/sample. This new study walks through optimization of a bunch of steps and gets to a really solid and approachable method...


...with great throughput! At 30SPD using DIA on a solid and pretty affordable workhorse of an instrument, these authors characterize the on- and off- target effects of 22 different drugs in record time.

The data on drugs we know about matches up really well with older data and adds a ton of credibility to the uncharacterized drugs. If you're just interested in the drug output data, it appears to all be up there on Zenodo here. 

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