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• Scalable detection of cellular protein-small molecule interactions via fluorescence anisotropy

  Authors: Qing Tang, Yuan-Ping Wei, Ruiqi Ma, Na Wei, Tammy Zihan Zhou, Hilary Kung-Yu Ho, Zafar Iqbal Bhat, Iqra Ishrat, Xiaoyu Li, Judy Wai Ping Yam, Yung Hou Wong, Qiankun Wang, Justin L. Tan

  Abstract:

  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,...

  Keywords: Fluorescence anisotropy; Protein Detection; Cellular Assays; Molecular Interactions; High-throughput Screening; Drug Discovery Innovation; Oncogene Targeting; PROTAC

  Timeline: First Posted 2026-01-30

  Metrics: Views: 139  |  Downloads: 34  |  Favorites: 0

• Cellular synthesis of ubiquitin-based probes for spatially resolved deubiquitinase profiling

  Authors: Jinghao Chen, Xinyu Zhang, Yang Huang, Gang Li, Yu-Hsuan Tsai

  Abstract:

  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...

  Keywords: Activity-based protein profiling; Deubiquitinase (DUB); Proximity-induced chemistry; Sortase A (SrtA); Ubiquitination

  Timeline: First Posted 2025-11-30

  Metrics: Views: 949  |  Downloads: 334  |  Favorites: 0

• Disulfide-directed multicyclic peptides for chimeric antigen receptors targeting solid tumors

  Authors: Xiaoting Meng, Keke Fu, Yawei Liu, Yuan Liu, Joe Zhang, Xi Kang, Chuanliu Wu, Yu-Hsuan Tsai

  Abstract:

  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...

  Keywords: CAR T; cyclic peptide; on-target, off-tumor toxicity; cytokine release syndrome; chimeric antigen receptor; disulfide-directed multicyclic peptide (DDMP)

  Timeline: First Posted 2025-11-25

  Metrics: Views: 856  |  Downloads: 276  |  Favorites: 1

  Now published in Journal of the American Chemical Society. doi: 10.1021/jacs.5c13642

• Mucinase-engineered cell membrane nanovesicles degrade the glycocalyx shield to potentiate antitumor immunity

  Authors: Xiaorui Geng, Silan Liu, Yuanwei Pan, Yun Ge, Lang Rao

  Abstract:

  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...

  Keywords: Glycoengineering; Nanobiotechnology; Cellular vesicles; Drug delivery; Cancer immunotherapy

  Timeline: First Posted 2025-11-19

  Metrics: Views: 905  |  Downloads: 356  |  Favorites: 3