Beschreibung:
<jats:title>Abstract</jats:title><jats:p>The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the <jats:italic>in vivo</jats:italic> analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic <jats:italic>Caenorhabditis elegans</jats:italic> expressing hTTR provide an optimal model for the <jats:italic>in vivo</jats:italic> identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of <jats:italic>Caenorhabditis elegans,</jats:italic> enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.</jats:p>