Investigations into linker effects of DNA–VHL ligand conjugates by multiplexed affinity measurements using focal molography

2026/01/01 by Pascal Raschke, Simona Notová, Volker Gatterdam +2 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Protein Degradation and Inhibitors #Click Chemistry and Applications #HER2/EGFR in Cancer Research

paper · pdf · doi:10.1039/d6cb00011h

openalex publication_date 2026/01/01 · openalex created_date 2026/03/20 · openalex updated_date 2026/06/11

Abstract

values. The multiplexed format achieves 20-fold higher throughput while yielding stronger structure-activity correlations with lipophilicity compared to singleplex measurements. Our analysis identifies hydrophobicity as the primary driver of the contribution of the linker part to overall linker-VHL ligand affinity for VHL in the case of DNA-PROTACs. These findings validate multiplexed FM as a robust platform for PROTAC structure-activity relationship studies and provide design principles for optimizing linker-E3 ligase interactions.

Discussions

• 📢 Out now in #RSCChemBio from Andreas Brunschweiger and his team at The University of Würzburg! ✨ Read about how they apply focal molography to characterise the binding of DNA-VHL ligands towards a [bsky, 0 points, 0 comments]

Related

• Proximity Binding Assay for PROTAC Ternary Complex Analysis
• Linker Histone Interaction Shows Divalent Character with both Supercoiled and Linear DNA
• Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity
• Linker Methylation as a Strategy to Enhance PROTAC Oral Bioavailability: Insights from Molecular Properties and Conformational Analysis
• Using environment-sensitive tetramethylated thiophene-BODIPY fluorophores in DNA probes for studying effector-induced conformational changes of protein–DNA complexes