Time-Resolved Hydrogen Deuterium Exchange Reveals the Structural Basis of Amyloidogenesis Inhibition by Alzheimer's Drug Candidates

摘要

Microfluidics-Enabled Time-Resolved Hydrogen/Deuterium Exchange (TRESI-HDX) Mass Spectrometry was implemented to study the mechanism of binding and inhibition of 3 potential anti-amyloid drugs (TRV301, 302, and 303) supplied by Treventis. When TRV301 was bound to tau, HDX profiles illustrated an increase in deuterium uptake across the sequence. TRV302 and TRV303 binds to tau at the hexapeptide II motif (aggregation-prone region), however induces different conformational changes.