Degradation of intrinsically disordered proteins using proteolysis targeting nanobody conjugate
Sun, X.; Wu, D.; Zhou, C.; Xia, S.; Chen, X.
Show abstract
Intrinsically disordered proteins (IDPs) play crucial roles in diverse cellular processes and are implicated in numerous diseases. However, due to the inherently unstructured nature, it is challenging to modulate their function using small molecule degraders or inhibitors. To address this, we introduced proteolysis targeting nanobody conjugate (PROTNC) composed of a nanobody that binds to an IDP, an E3 ligase ligand, and a cyclic cell-penetrating peptide for efficient intracellular delivery. We first showed a general-purpose PROTNC system capable to degrade different endogenous IDPs based on a co-condensate formation mechanism. We also introduced a straightforward strategy to degrade individual IDPs using specific PROTNCs equipped with a nanobody recognizing that particular IDP. Notably, we demonstrated the degradation of TPX2 which is an undruggable oncogenic IDP responsible for microtubule nucleation. This targeted degradation effectively inhibited cancer cell proliferation by disrupting bipolar mitotic spindle assembly in metaphase and directed cells to apoptotic pathway.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Engineering of a fluorescent chemogenetic reporter with tunable color for advanced live-cell imaging 96%
- Enhancing Intracellular Accumulation and Target Engagement of PROTACs with Reversible Covalent Chemistry 96%
- Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2 96%
Similar papers in this journal
- Optimized pipeline for generating highly potent neutralizing Affitins: application to SARS-CoV-2 spike protein 95%
- Enzymatic Assembly for CRISPR Split-Cas9 System: The Emergence of a Sortase-based Split-Cas9 Technology 93%
- Oxygen-induced chromophore degradation in the photoswitchable red fluorescent protein rsCherry 93%
Similar papers in this journal
Similar papers in this journal
- Targeting c-Myc with a novel Peptide Nuclear Delivery Device 96%
- A novel epitope tagging system to visualize and monitor antigens in live cells with chromobodies 96%
- Coiled-coil heterodimers with increased stability for cellular regulation and sensing SARS-CoV-2 spike protein-mediated cell fusion 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.