Techniques: Intact protein mass spectrometry (IPMS)-based measurement of inhibitor-proteasome subunit binding

An IPMS-based platform could help identify the binding specificity to proteasome subunits for small molecule therapies. The platform utilized HPLC separation of proteasome subunits, high-resolution IPMS and automated data deconvolution to generate 2D maps of subunit mass against retention time. Analysis of a 14-subunit human proteasome showed that pretreatment with carfilzomib induced shifts in the map positions of the β1c, β2c, and β5c subunits, indicative of subunit-drug binding, compared with no pretreatment. Next steps could include testing additional proteasome inhibitors...