Results 81 to 90 of about 8,212 (230)

Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing

Advanced Science, EarlyView.
Targeted chimeric degraders engage extracellular or membrane proteins and endocytosable cell‐surface receptors, forming ternary complexes that induce receptor‐mediated internalization. Following endocytosis, post‐endocytic sorting—not internalization alone—determines target fate.
Ke Liu, Xiyan Wang, Xiaozhen Liu, Chaoqi He, Da Qian, Xuli Meng, Liquan Zhu   +6 more
wiley   +1 more source

Chemical Synthesis and Functional Screening of an 800 000‐Member Library Using a Peptide‐Pairing Strategy

Angewandte Chemie, EarlyView.
Chemical peptide synthesis allows the generation of structurally highly diverse compounds suited for ligand development, but current methods in parallel peptide synthesis limit the achievable library size to a few thousand. A strategy is presented based on combinatorial pairing of short peptides via disulfide linkage that enables the generation and ...
Anne Zarda, Xingwang Deng, Edward Will, Thomas Emel, Maylin Romero, Christian Heinis   +5 more
wiley   +2 more sources

Palmitoyl Acyltransferase Zdhhc17 Promotes Functional Recovery After Spinal Cord Injury by Targeting the Nuclear Transport Factors Kpna2 and Ipo9

Advanced Science, EarlyView.
In this study, we demonstrate that Zdhhc17, acting as a PAT, suppresses neuronal apoptosis and promotes axon regeneration after injury, thereby enhancing functional recovery following SCI. In this context, Kpna2 and Ipo9 serve as novel palmitoylation substrates of Zdhhc17, whose palmitoylation prevents the injury‐induced degradation of their proteins ...
Meixuan Chen, Huan Chen, Sining Ding, Fan Liu, Xiaofei Zheng, Yuan Wang, Ruitu Tian, Huan Li, Peilin Liu, Le Hu, Bin Liu, Limin Rong, Mangmang Li   +12 more
wiley   +1 more source

A Versatile DNA‐Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity

Advanced Science, EarlyView.
We present a versatile DNA‐encoded library (DEL) platform designed for rapid library synthesis and subsequent screening for chemical inducers of proximity (CIPs) across various presenter proteins of choice. Applying this approach, we discovered a novel molecular glue‐like compound mediating CRBN‐BRD9 ternary complex formation with remarkable ...
Bingqi Tong, Sunny A. Tang, Yifan Deng, Zhihan Nan, Alison X. Gao, Gregory A. Michaud, Simone Bonazzi, Frédéric Berst, Frédéric J. Zécri, Shuang Liu, William J. Gibson, Stuart L. Schreiber   +11 more
wiley   +1 more source

TROP2‐Targeting Chimeras (TRTACs) for Tumor Cell‐Selective Membrane Protein Degradation and Enhanced Drug Delivery

Advanced Science, EarlyView.
TROP2 is identified as a novel tumor‐selective lysosomal‐targeting receptor with established clinical relevance. TROP2‐targeting chimeras (TRTACs) are developed by genetically fusing a TROP2‐binding nanobody to nanobodies against specific target proteins.
Luping Chen, Xinying Fu, Wenqian Dong, Xiaobei Deng, Simin Chen, Fujun Wang, Jian Zhao, Shiqun Shao, Liqiang Fan, Jingyu Zhang, Lixin Zhang   +10 more
wiley   +1 more source

Degrading GPX4 via Biomimetic Nanoparticle‐Mediated In Situ Synthesis of Deep‐Learning‐Designed Binder‐Degron Chimeras for Prostate Cancer Therapy

Advanced Science, EarlyView.
A deep‐learning‐designed binder is fused to a combinatorial degron to create a binder‐degron chimera (bdC) that recruits the CUL2‐RING ubiquitin ligase complex. Encapsulation in a prostate‐cancer‐targeted, CD47‐camouflaged nanocarrier enables tumor‐specific in situ bdC expression, triggering GPX4 degradation and ferroptosis, thereby establishing a ...
Si‐Han Zhang, Ye An, Na Zeng, Mei‐Cheng Liu, Jian‐Xuan Sun, Xi Gong, Jin‐Zhou Xu, Shao‐Gang Wang, Qi‐Dong Xia   +8 more
wiley   +1 more source

PROTAC-DB 3.0: an updated database of PROTACs with extended pharmacokinetic parameters

Nucleic Acids Research
Abstract Proteolysis-targeting chimera (PROTAC) is an emerging therapeutic technology that leverages the ubiquitin-proteasome system to target protein degradation. Due to its event-driven mechanistic characteristics, PROTAC has the potential to regulate traditionally non-druggable targets.
Jingxuan Ge, Shimeng Li, Gaoqi Weng, Huating Wang, Meijing Fang, Huiyong Sun, Yafeng Deng, Chang- Yu Hsieh, Dan Li, Tingjun Hou   +9 more
openaire   +2 more sources

Transfer RNA‐Derived Small RNA‐5’tiRNAGln Drives HNRNPC Phase Separation to Promote Breast Cancer Bone Metastasis by Regulating IGF1R

Advanced Science, EarlyView.
This study reveals that 5'tiRNA‐Gln interacts with hnRNPC to promote IGF1R liquid‐liquid phase separation, which drives ERK1/2 signaling activation, EMT, and breast cancer bone metastasis. These findings highlight a novel mechanism of breast cancer bone metastasis and potential therapeutic target in metastatic breast cancer.
Bingnan Wang, Dongsong Liu, Xiaozhi Fan, Jiale Fan, Xuesi liu, Yu Wang, Zixin Wang, Mo Cheng, Ping Zhou, Wangjun Yan   +9 more
wiley   +1 more source

mRNA PROTACs: engineering PROTACs for high‐efficiency targeted protein degradation

MedComm
AbstractProteolysis‐targeting chimeras (PROTACs) are essential bifunctional molecules that target proteins of interest (POIs) for degradation by cellular ubiquitination machinery. Despite significant progress made in understanding PROTACs' functions, their therapeutic potential remains largely untapped.
Xiaoqi Xue, Chen Zhang, Xiaolin Li, Junqiao Wang, Haowei Zhang, Ying Feng, Naihan Xu, Hongyan Li, Chunyan Tan, Yuyang Jiang, Ying Tan   +10 more
openaire   +3 more sources

PROTAC-Induced Proteolytic Targeting [PDF]

, 2012
Small-molecule modulators of protein activity are increasingly being utilized as tools to examine the functional roles of proteins. Operating at the post-translational level, these molecules provide enhanced temporal and spatial control and mitigate the potential for compensatory responses in comparison with classical genetic approaches.
Kimberly Cornish, Carmony, Kyung-Bo, Kim
openaire   +2 more sources