Design and Validation of Autophagy Targeting Chimeras (AUTAC)

该提案描述了一个集计算建模、化学和生物学于一身的项目。我们的目标是开发一类新的化合物，用于探索细胞和组织中自噬的调节。具体地说，我们的目标是开发基于PROTAC(PROTAC)设计的化合物。PROTAC是一种嵌合的小分子，它将货物蛋白与蛋白酶体的降解机制联系起来，允许蛋白酶体中的心包被降解。我们计划设计新型的PROTAC来调节货物的溶酶体脱脂作用，允许应用于降解细胞中更大的大复合体，如线粒体。

This proposal describes a project at the interface of computational modeling, chemistry andbiology. We aim to develop a novel class of chemical compounds for probing the regulation ofautophagy in cells and tissues. Specifically, we aim to develop compounds that are based onPROteolysis TArgeting Chimera (PROTAC) design. PROTACs are chimeric small molecules thatlink a cargo protein to the proteasomal degradation machinery, allowing degradation of thecargo in the proteasome. We plan to design novel PROTACs that mediate lysosomaldegaradation of cargo, allowing applications for the degradation of much largermacrocomplexes in cells such as mitochondria.