Dodero Verónica I, Herrera María G
Department of Chemistry, Bielefeld University, Universitätsstr. 25, 33615, Bielefeld, Germany.
Molecular Cell Biology, Faculty of Medicine, Ruhr University Bochum, Universitätsstr. 150, 44801, Bochum, Germany.
ChemMedChem. 2025 Mar 15;20(6):e202400789. doi: 10.1002/cmdc.202400789. Epub 2024 Dec 20.
The 33-mer gliadin peptide and its deamidated derivative, known as 33-mer DGP, are proteolytically resistant peptides central to the pathomechanism of celiac disease (CeD), the autoimmune presentation of gluten-related disorders (GRD). Both peptides can form spontaneous oligomers in the nanomolar concentration, leading to the formation of nanostructures. In other protein-related diseases, oligomers and aggregates are central in their pathomechanism; therefore, it was hypothesized that the oligomerization of proteolytical-resistant 33-mer gliadin peptides could be an underrecognized disease trigger. This review focuses on the current understanding of 33-mer peptides and their oligomers in vitro and cellular experiments. We intend to give the necessary details that incentivize the chemistry community to get involved in the effort to understand the self-assembly of gliadin peptides and the role of their supramolecular structures in CeD and the other GRD. More research is needed to design effective and safe chemical and/or nutritional interventions beyond the gluten-free diet.
33 肽麦醇溶蛋白及其脱酰胺衍生物（称为 33 肽 DGP）是乳糜泻（CeD）发病机制的核心抗蛋白水解肽，CeD 是麸质相关疾病（GRD）的自身免疫表现形式。这两种肽在纳摩尔浓度下都能形成自发寡聚体，导致纳米结构的形成。在其他与蛋白质相关的疾病中，寡聚体和聚集体是其发病机制的核心；因此，有人推测抗蛋白水解的 33 肽麦醇溶蛋白肽的寡聚化可能是一种未被充分认识的疾病触发因素。本综述重点关注目前在体外和细胞实验中对 33 肽及其寡聚体的理解。我们打算提供必要的细节，激励化学界参与到了解麦醇溶蛋白肽自组装及其超分子结构在 CeD 和其他 GRD 中的作用的工作中来。除了无麸质饮食外，还需要更多研究来设计有效且安全的化学和/或营养干预措施。
