Actually tell if it is an ADP-r or a PolyADP-r with insanely hard sample prep!

 

If you're ever feeling really good about your skills as a proteomic mass spectrometrist and need knocked down a peg, I strongly recommend going into the amazing field of ADP-Ribosylation. This amazing modification can be one ADPr or long chains of repeated ADPr. Sounds fun, right? 

Glycoproteomics is great because there are like 1-4 sugars for each mass and they can go on like 5 amino acids? I forget, and each sugar chain can break in like 2 or 3 places. 

ADPr cranks up the fun by each monomer fragmenting in 7 possible places, the mod can exist on 11 different amino acids and - again - each monomer has the exact same mass. 

Look at this awful thing (from this great JASMS paper from a couple years ago) 

Sign me up for citrullination on an Orbitrap (please don't) or phospho vs sulfation vs nitration on a TOF (for real, no, please don't) any day of the week. 

So Anthony and Isabel had this great idea of MAKING THIS HARDER. Because the way people do it is to cleave it down to a much smaller mod, so you know that there was an ADPr, but you don't know if it was one or a chain. 

It took a village - and maybe like 5 years (including pandemic times which we all know like only sorta counts) but Isabel actually pulled it off. 

To really get it to work - you need that ETD + HCD (EThcD?) thing that you can only get on Tribrids. And while the preliminary work on Chan-Hyun Lab Lumos(es) looked good, you can really see the benefits of the enhanced signal and improved fragmentation dynamics on the Eclipse in Ben Garcia's lab. This didn't make the manuscript - but - wow - does this stuff look better with the labile mod workflows in the newer MSFraggers and huge thanks to Dan and Alexey's team for extra help setting those processing things up.