Cell Membrane as A Promising Therapeutic Target: From Materials Design to Biomedical Applications DOI
Xiaofeng Wu, Jingjing Hu, Juyoung Yoon

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(18)

Published: Feb. 19, 2024

Abstract The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction information exchange. Therefore, disrupting its structure or impairing functions can potentially cause irreversible damage. Presently, the tumor recognized as promising therapeutic target for various treatment methods. Given extensive research focused on membranes, it both necessary timely to discuss these developments, from materials design specific biomedical applications. This review covers treatments based functional targeting membrane, ranging well‐known membrane‐anchoring photodynamic therapy recent lysosome‐targeting chimaeras protein degradation. diverse mechanisms are introduced in following sections: phototherapy, self‐assembly situ biosynthesis degradation proteins by chimeras. In each section, we outline conceptual general derived numerous studies, emphasizing representative examples understand advancements draw inspiration. Finally, some challenges future directions membrane‐targeted our perspective. aims engage multidisciplinary readers encourage researchers related fields advance fundamental theories practical applications membrane‐targeting agents.

Language: Английский

Extracellular targeted protein degradation: an emerging modality for drug discovery DOI
James A. Wells, Kaan Kumru

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 23(2), P. 126 - 140

Published: Dec. 7, 2023

Language: Английский

Citations

65
Dendronized DNA Chimeras Harness Scavenger Receptors To Degrade Cell Membrane Proteins DOI

Chenghong Zhu,

Weishan Wang, Yan Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Feb. 3, 2023

Abstract Bispecific chimeras bridging cell membrane proteins with lysosome‐trafficking receptors (LTRs) provide an effective therapeutic approach through lysosomal degradation of disease‐relevant targets. Here, we report a novel dendronized DNA chimera (DENTAC) strategy that uses dendritic to engage surface scavenger (SRs) as LTR. Using bioorthogonal strain‐promoted alkyne‐azide cycloaddition conjugate the protein binder, resulting DENTAC is able traffic target into lysosome for elimination. We demonstrated utility by degrading oncogenic nucleolin (NCL) and epidermal growth factor receptor (EGFR). The anti‐cancer application NCL‐targeting was validated in mouse xenograft model lung cancer. This work thus presents new avenue rapid development potent degraders against proteins, also broad research prospects.

Language: Английский

Citations

47
Transferrin receptor targeting chimeras for membrane protein degradation DOI
Dingpeng Zhang, Jhoely Duque-Jimenez, Francesco Facchinetti

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

Language: Английский

Citations

30
Targeted protein degradation directly engaging lysosomes or proteasomes DOI Creative Commons
Jiseong Kim, Insuk Byun, Do Young Kim

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(7), P. 3253 - 3272

Published: Jan. 1, 2024

This review delineates emerging technologies for targeted protein degradation that directly involve lysosomes or proteasomes. It explores their unique features, advantages, and limitations, offering perspectives on future therapeutic applications.

Language: Английский

Citations

28
Cell Membrane as A Promising Therapeutic Target: From Materials Design to Biomedical Applications DOI
Xiaofeng Wu, Jingjing Hu, Juyoung Yoon

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: Feb. 19, 2024

The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction information exchange. Therefore, disrupting its structure or impairing functions can potentially cause irreversible damage. Presently, the tumor recognized as promising therapeutic target for various treatment methods. Given extensive research focused on membranes, it both necessary timely to discuss these developments, from materials design specific biomedical applications. This review covers treatments based functional targeting membrane, ranging well-known membrane-anchoring photodynamic therapy recent lysosome-targeting chimaeras protein degradation. diverse mechanisms are introduced in following sections: phototherapy, self-assembly situ biosynthesis degradation proteins by chimeras. In each section, we outline conceptual general derived numerous studies, emphasizing representative examples understand advancements draw inspiration. Finally, some challenges future directions membrane-targeted our perspective. aims engage multidisciplinary readers encourage researchers related fields advance fundamental theories practical applications membrane-targeting agents.

Language: Английский

Citations

19
Chemically engineered antibodies for autophagy-based receptor degradation DOI

Binghua Cheng,

Meiqing Li, Jiwei Zheng

et al.

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

2
The rise of degrader drugs DOI Creative Commons
Mingxing Teng, Nathanael S. Gray

Cell chemical biology, Journal Year: 2023, Volume and Issue: 30(8), P. 864 - 878

Published: July 25, 2023

Language: Английский

Citations

30
Insulin-like Growth Factor 2 (IGF2)-Fused Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins DOI
Bei Zhang, Rajeev Kungur Brahma,

Liquan Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24272 - 24283

Published: Oct. 30, 2023

Targeted degradation of the cell-surface and extracellular proteins via endogenous lysosomal pathways, such as lysosome-targeting chimeras (LYTACs), has recently emerged an attractive tool to expand scope chemical biology. Herein, we report a series recombinant genetically fused insulin-like growth factor 2 (IGF2), which termed iLYTACs, that can be conveniently obtained in high yield by standard cloning bacterial expression matter days. We showed both type-I IGF2 was suitable affibody or nanobody capable binding specific protein target, type-II iLYTAC (or IGF2-Z), IgG-binding Z domain served universal antibody-binding adaptor, could used for effective targeting various membrane-bound proteins-of-interest. These heterobifunctional iLYTACs are fully encoded produced on large scale from conventional E. coli systems without any form modification. In current study, successfully facilitated cell uptake, localization, efficient disease-relevant targets different mammalian lines, including EGFR, PD-L1, CD20, α-synuclein. The antitumor properties were further validated mouse xenograft model. Overall, represent general modular strategy convenient selective targeted degradation, thus expanding potential applications LYTACs related techniques.

Language: Английский

Citations

24
A co-assembly platform engaging macrophage scavenger receptor A for lysosome-targeting protein degradation DOI Creative Commons
Qian Wang, Xingyue Yang,

Ruixin Yuan

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 23, 2024

Abstract Targeted degradation of proteins has emerged as a powerful method for modulating protein homeostasis. Identification suitable degraders is essential achieving effective degradation. Here, we present non-covalent degrader construction strategy, based on modular supramolecular co-assembly system consisting two self-assembling peptide ligands that bind cell membrane receptors and the interest simultaneously, resulting in targeted The developed lysosome-targeting co-assemblies (LYTACAs) can induce lysosomal extracellular IL-17A PD-L1 several scavenger receptor A-expressing lines. IL-17A-degrading been applied an imiquimod-induced psoriasis mouse model, where it decreases levels skin lesion alleviates psoriasis-like inflammation. Extending to asialoglycoprotein receptor-related degradation, LYTACAs have demonstrated versatility potential streamlining proteins.

Language: Английский

Citations

16
Development of Integrin-Facilitated Bispecific Aptamer Chimeras for Membrane Protein Degradation DOI

Weidi Sun,

Hui Zhang,

Wanlin Xie

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(37), P. 25490 - 25500

Published: Sept. 3, 2024

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level commonly used receptors (LTRs) varies different cell lines, thus limiting broad applications LYTACs. To overcome this difficulty, we herein report development integrin α3β1 (ITGA3B1)-facilitated bispecific aptamer (ITGBACs) as platform proteins. ITGBACs consist two aptamers, one targeting ITGA3B1 another binding to membrane-associated interest (POI), effectively transporting POI into lysosomes degradation. Our findings demonstrate that eliminate pathological proteins, such CD71 PTK7, inducing significant cell-cycle arrest apoptosis markedly inhibiting tumor growth tumor-bearing mice models. Therefore, work provides novel versatile platform, offering targeted therapy tumor-specific LTRs.

Language: Английский

Citations

10