Controllable multivalent LYTACs enhance targeted protein degradation

Controllable multivalent LYTACs enhance targeted protein degradation

We present a versatile DNA-based LYTAC framework that allows control over the valency of chimeras and the distance between ligands through DNA self-assembly. By evaluating the degradation capabilities of LYTACs with 1, 3, and 9 valences, we confirm the broad applicability of the multivalent enhancem...

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Veröffentlicht in:Chemical communications (Cambridge, England) England), 2025-01, Vol.61 (3), p.580-583
Hauptverfasser: Lv, Yuheng, Li, Yicun, Fu, Qin, Shi, Peng
Format: Artikel
Sprache:eng
Schlagworte:
Controllability
Degradation
DNA - chemistry
DNA - metabolism
Humans
Ligands
Lysosomes - chemistry
Lysosomes - metabolism
Proteolysis
Self-assembly
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Zusammenfassung:We present a versatile DNA-based LYTAC framework that allows control over the valency of chimeras and the distance between ligands through DNA self-assembly. By evaluating the degradation capabilities of LYTACs with 1, 3, and 9 valences, we confirm the broad applicability of the multivalent enhancement effect across different lysosome-targeting receptor-mediated degradation pathways. Our findings provide valuable insights into improving the degradation efficiency of LYTACs.
ISSN:1359-7345
1364-548X
1364-548X
DOI:10.1039/d4cc04842c