ArticleJournal of medicinal chemistry2026
Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication.
Article in Journal of medicinal chemistry, 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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Abstract
DCAF1 is a donut shaped WD40 repeat protein and a substrate receptor of two distinct E3 ligases. In HIV-1 infection, the viral protein Vpr binds to the top surface of DCAF1, changes its substrate specificity to degrade human proteins involved in antiviral activities, enabling HIV-1 to replicate. We hypothesized that artificial top-to-top self-dimerization of DCAF1 could result in DCAF1 loss-of-function and blocking of the Vpr-DCAF1 interaction. We designed and synthesized seven compounds we call SDIPTACs (Self-dimerization Induced Proximity Targeting Chimeras) which artificially induce DCAF1 self-dimerization through the Vpr interaction surface. Interestingly, SDIPTACs C8 and C9, inhibited Vpr-dependent HIV replication in CD4
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