Design and Validation of Autophagy Targeting Chimeras (AUTAC)

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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.