ArticleRSC chemical biology2026
Investigations into linker effects of DNA-VHL ligand conjugates by multiplexed affinity measurements using focal molography.
Article in RSC chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
The determination of kinetic binding properties of DNA-tagged compounds binding to a target protein is an important step in the development of nucleic acid-based PROTACs. Focal molography (FM) is a recent addition to the toolbox of instruments that allow for measuring kinetic binding data of drugs binding to a target protein with high experimental throughput. Here, we applied focal molography to characterize the binding of DNA-VHL ligand conjugates-these are "DNA-PROTAC" compounds-to VHL. We synthesized two libraries of 20 such compounds with diverse amino acid linkers by solid-phase amide coupling and used FM to measure their affinity to VHL in both singleplex and 20-plex multiplexed measurement formats. Systematic comparison of equilibrium and kinetic fitting approaches reveals strong within-format correlations that preserve compound rankings despite systematic offsets in absolute
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