Celiac Disease (CD) is now recognized as a worldwide epidemic. Although a gluten free diet usually induces clinical improvements within days or weeks, adhering to this routine is still troublesome. Therefore, new solutions are needed for quality-of-life improvement of CD patients. The present work intends to bring molecular and thermodynamic insights on the ability of green tea epigalhocatechin-3-gallate (EGCG) to interact and modulate the bioavailability of a major CD immunodominant peptide (32-mer). Characterization of peptide binding was assessed by means of both 1D and 2D 1H NMR experiments, ITC and Molecular Dynamics simulations. Accordingly, EGCG not only exhibits a high reactivity towards the 32-mer peptide as its binding appears to be entropy-driven and involves two sequential binding events, each with different binding strengths. Structural rearrangements were also detected during the interaction, contributing to a greater stability of the formed complexes. In vitro transepithelial transport assays using a Caco-2 cell line model were also performed and highlighted the ability of EGCG to significantly reduce the concentration of free peptide in the basolateral compartment. Overall, this study provides important evidences regarding the structural features and molecular mechanisms by which EGCG could interact and potentially modulate the function of some bioactive CD peptides.
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