化学生物学
所有项目
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摘要:
Proteolysis Targeting Chimera (PROTACs) are a revolutionary drug modality that can expand the repertoire of druggable targets to proteins lacking conventional active sites or binding pockets1. However, the majority of PROTACs developed are against already drugged targets2 suggesting it is challenging to discover novel binders of undruggable targets. To overcome this, we developed a scalable,...
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摘要:
Deubiquitinases (DUBs) orchestrate ubiquitin homeostasis, yet their compartment-specific activities remain underexplored. We developed a genetically encoded strategy to assembly activity-based ubiquitin probes in cellulo via sortase A (SrtA)-mediated transpeptidation. Co-targeting SrtA and its ubiquitin substrate to the outer mitochondrial membrane reduced off-target transpeptidation and enabled...
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摘要:
The clinical application of chimeric antigen receptor (CAR) T cell therapy in solid tumors remains limited due to significant safety concerns, particularly “on-target, off-tumor” toxicity and cytokine release syndrome (CRS). Here, we describe a class of CARs that employ disulfide-directed multicyclic peptides (DDMPs) as compact antigen-recognition domains targeting the tumor-associated antigens...
现已发表于 Journal of the American Chemical Society. doi: 10.1021/jacs.5c13642 -
摘要:
The tumor glycocalyx forms a protective shield that masks checkpoint proteins and compromises the efficacy of immunotherapies. While the bacterial protease StcE can degrade this barrier by cleaving O-glycosylated mucin domains, its therapeutic potential is hindered by off-target toxicity and high immunogenicity. To overcome these limitations, we developed a biomimetic platform of cell membrane...