Synthesis, Biosynthesis and Mode-of-Action of Fungal Cyclopeptides

一种小分子和各种环肽被描述为与蘑菇中毒有关。到目前为止，化学合成和生物合成以及潜在的作用模式和分子靶标结构都是未知的。在初步实验的基础上，在这个来自肽(生物)化学和细胞生物学的实验室的联合项目中，我们将调查来源，以便可能找到对所观察到的生理效应的解释。该项目包括环肽的化学合成，寻找生物合成的来源，基于类似物的化学合成的结构-活性-关系，寻找被寻址的受体(S)和靶结构，以及参与水通道蛋白-2在细胞质和膜之间的重新分配。对作用模式的澄清可作为药物开发的基础。

A small molecule and various cyclopeptides have been described to be related to intoxications from mushrooms. The chemical synthesis and the biosynthesis are unknown to date, as well as the underlying mode-of-action and the molecular target structures. Based on initial experiments, in this joint project between labs from peptide (bio)chemistry and cell biology we will investigate the origins in order to possibly find explanations for the observed physiological effects. The project comprises the chemical synthesis of the cyclopeptides, the search for the biosynthetic origin, structure-activity-relations based on the chemical synthesis of analogs, the search for the addressed receptor(s) and target structures, as well as the involvement of redistribution of the water channel aquaporin-2 between cytoplasm and membrane. The clarification of the modes-of-action could be the basis for the development of drugs.