biostudies-literatureUnknown16(1)Kapcan EA special class of proximity inducing bifunctional molecules/chimeras called molecular glues leverage positive co-operativity to stabilize ternary complex formation and induce a biological response. Despite their utility, molecular glues remain challenging to rationally design. This is particularly true in the context of inducing cell-cell proximity which involve ternary complexes that comprise non- or negatively interacting proteins. In this work, we develop a dual proximity labeling strategy enabling a chimera to covalently crosslink a non-interacting serum antibody to a tumor surface protein, within a ternary complex. The resultant resistance to dissociation, including in the presence of competitor binding ligands, mimics molecular glue stabilization. We demonstrate these covalent glue Nature communications2855https://www.ebi.ac.uk/biostudies/studies/S-EPMC11933337biostudies-literatureMimicry of molecular glues using dual covalent chimeras.PMC11933337Rullo AFKrygier Kda Luz MSerniuck NJZhang AKapcan EBramson JfalseMimicry of molecular glues using dual covalent chimeras.A special class of proximity inducing bifunctional molecules/chimeras called molecular glues leverage positive co-operativity to stabilize ternary complex formation and induce a biological response. Despite their utility, molecular glues remain challenging to rationally design. This is particularly true in the context of inducing cell-cell proximity which involve ternary complexes that comprise non- or negatively interacting proteins. In this work, we develop a dual proximity labeling strategy enabling a chimera to covalently crosslink a non-interacting serum antibody to a tumor surface protein, within a ternary complex. The resultant resistance to dissociation, including in the presence of competitor binding ligands, mimics molecular glue stabilization. We demonstrate these covalent glue 2025-01-01T00:00:00Z2025 Mar2026-06-01T06:10:05.231Z2026-04-08T09:46:56.563ZS-EPMC119333374012852810.1038/s41467-025-58083-z