Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1
| Autor: | Adam D. Cotton, Josef A. Gramespacher, James A. Wells, Duy P. Nguyen, Ian B. Seiple |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Protein degradation
010402 general chemistry 01 natural sciences Biochemistry Catalysis Antibodies B7-H1 Antigen law.invention Colloid and Surface Chemistry Ubiquitin law Humans biology Chemistry Communication General Chemistry Small molecule Immune checkpoint 0104 chemical sciences Cell biology Ubiquitin ligase Proteostasis Chemical Sciences Proteolysis Recombinant DNA biology.protein Generic health relevance Target protein Biotechnology |
| Zdroj: | Journal of the American Chemical Society Journal of the American Chemical Society, vol 143, iss 2 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Targeted protein degradation has emerged as a new paradigm to manipulate cellular proteostasis. Proteolysis-targeting chimeras (PROTACs) are bifunctional small molecules that recruit an E3 ligase to a target protein of interest, promoting its ubiquitination and subsequent degradation. Here, we report the development of antibody-based PROTACs (AbTACs), fully recombinant bispecific antibodies that recruit membrane-bound E3 ligases for the degradation of cell-surface proteins. We show that an AbTAC can induce the lysosomal degradation of programmed death-ligand 1 by recruitment of the membrane-bound E3 ligase RNF43. AbTACs represent a new archetype within the PROTAC field to target cell-surface proteins with fully recombinant biological molecules. |
| Databáze: | OpenAIRE |
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