biostudies-literatureZheng TBrown UniversityHuman Frontier Science ProgramHHS | NIH | National Institute of General Medical SciencesALS AssociationALS Association (ALSA)National Science Foundation (NSF)Human Frontier Science Program (HFSP)Brown University (BU)HHS | NIH | National Institute of General Medical Sciences (NIGMS)NIGMS NIH HHSNational Science Foundation2725-2740https://www.ebi.ac.uk/biostudies/studies/S-EPMC12084347biostudies-literatureUnknown44(10)The alkanediol 1,6-hexanediol has been widely used to dissolve liquid-liquid phase-separated condensates in cells and in vitro, but the details of how it perturbs the molecular interactions underlying liquid-liquid assembly remain unclear. In this study we use a combination of microscopy, nuclear magnetic resonance (NMR) spectroscopy, molecular simulation, and biochemical assays to probe how alkanediols suppress phase separation and why certain isomers are more effective. We show that alkanediols of different lengths and configurations are all capable of disrupting phase separation of the RNA-binding protein Fused in Sarcoma (FUS), although potency varies depending on both geometry and hydrophobicity, which we measure directly. Alkanediols induce a shared pattern of changes to the chemicalThe EMBO journalMolecular insights into the effect of 1,6-hexanediol on FUS phase separation.PMC120843471644760Pape Adams Postdoctoral Award from the Carney Institute1845734T32 GM007601T32 GM13656623-PDF-629RGP0045/2018T32GM139793T32 GM139793T32GM136566R01 GM147677T32GM007601R35 GM153388R01GM147677R35GM153388Fawzi NLWeng SLPerdikari TMMittal JWake NZheng TMurthy ACfalseMolecular insights into the effect of 1,6-hexanediol on FUS phase separation.The alkanediol 1,6-hexanediol has been widely used to dissolve liquid-liquid phase-separated condensates in cells and in vitro, but the details of how it perturbs the molecular interactions underlying liquid-liquid assembly remain unclear. In this study we use a combination of microscopy, nuclear magnetic resonance (NMR) spectroscopy, molecular simulation, and biochemical assays to probe how alkanediols suppress phase separation and why certain isomers are more effective. We show that alkanediols of different lengths and configurations are all capable of disrupting phase separation of the RNA-binding protein Fused in Sarcoma (FUS), although potency varies depending on both geometry and hydrophobicity, which we measure directly. Alkanediols induce a shared pattern of changes to the chemical2025-01-01T00:00:00Z2025 May2026-06-03T02:39:06.534Z2026-04-23T03:11:04.513ZS-EPMC120843474028135710.1038/s44318-025-00431-2