ATNC: Versatile Nanobody Chimeras for Autophagic Degradation of Intracellular Unligandable and Undruggable Proteins.

ABSTRACT: Targeted protein degradation (TPD) through the autophagy pathway displays broad substrate scope and is gaining increasing interest in biology and medicine. However, current approaches using small-molecule degraders have limitations due to the lack of versatility, modularity, and ease of implementation and are restricted to addressing only ligandable proteins. Herein, we report a nonsmall molecule-based autophagy-targeting nanobody chimera (ATNC), or phagobody, for selective degradation of intracellular targets, which overcomes these limitations. The core of an ATNC features a nanobody for recruiting proteins as well as an autophagic pathway-directing module. ATNC turns out to be a general, modular, and versatile degradation platform. We show that ATNC can be versatilely implemented in diff

SUBMITTER: He H 

PROVIDER: S-EPMC10655170 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature