Wednesday, April 12, 2023

Applying isobaric carrier channels to direct drug-protein target (thermo profiling) assays!

 

This paper is dense dense dense, but if you are interested in characterizing drug-protein interactions and using things like thermal protein profiling, you're going to love this


A lot of the newer direct drug-target stuff uses different temperatures for unfolding the proteins prior to digestion and we've seen how valuable multiplexing can be for those.

This study breaks out a lot of newer technology, including phase constraint, but the first thing that stands out is the use of isobaric carrier channels. By having that secondary carrier (which is referred to as SIILCC, here) this group shows a dramatic improvement in data quality. Normally we're using that to boost our signal for incredibly low abundance things, and we know the limitations for those. Here, however, they could realistically just add more material, they aren't incredibly limited. 

Where this really truly shines is in the increase in data completeness. Having this higher abundance pool in the carrier channel reduces the number of missing values and makes the data a whole lot easier ot work with. 

In a case where you're trying to determine "did this drug alter the melting point/thermal stability of protein X" NOT TRIGGERING an MS2 on a peptide of interest can make that whole LCMS run pretty much useless. 

Altogether this is just a really clever way to leverage an isobaric carrier channel in a new-ish way to improve the data in really tough and extremely valuable experiments. 

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