A Combined High-Resolution Mass Spectrometric and in silico Approach for the Characterisation of Small Ligands of β2-Microglobulin

beta(2) Microglobulin (beta(2)-m) is a protein responsible for a severe complication of long term hemodialysis, known dialysis related amyloidosis in which intial beta(2)-m misfolding leads to amyloid fibril deposition mainly in the skeletal tissue. Whereas much attention is paid to understanding the complex mechanism of amyloid formation the evaluation of small molecules that may bind beta(2)-m and possibly inhibit the aggregation process is still largely unexplored mainly because the protein lacks a specific active site. Based on our previous findings, we selected a pilot set of sulfonated molecules that are known to either bind or not to the protein, including binders that are anti amyloidogenic. We show how a complementary approach fusing high resolution mass spectrometry and in silicon studies, can offer rapid and precise information on affinity as well as in sight into the structurel requisites that favour or disfavour the inhibitory activity. Overall this approach can be used for predictive purposes and for a rapid screening of fibrillogenesis in hibitors.