Design and Validation of Autophagy Targeting Chimeras (AUTAC)

该提案描述了一个在计算建模，化学和生物学接口的项目。我们的目标是开发一类新的化合物，用于探测细胞和组织中自噬的调节。具体来说，我们的目标是开发基于PROteolysis Targeting Chimera（PROTAC）设计的化合物。PROTAC是一种嵌合的小分子，它将货物蛋白连接到蛋白酶体降解机制上，使货物蛋白在蛋白酶体中降解。我们计划设计新型的PROTAC，介导溶酶体对货物的脱保护，从而可以应用于细胞（如线粒体）中更大的大复合物的降解。

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.