ArticleNature communications2025
Mimicry of molecular glues using dual covalent chimeras.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Targeting Adaptive and Innate Immune Responses with Covalent Aptamers.Journal of the American Chemical Society · 2026Article
- Nanobody-Based Bioconjugates as Potent and Broadly Active Inhibitors of HIV Entry.Journal of the American Chemical Society · 2026Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- PROTACs in cancer immunotherapy: a minireview.Biochemical Society transactions · 2025Review
- Advances in sulfonyl exchange chemical biology: expanding druggable target space.Chemical science · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 mimics (CGMs) can induce cell-cell proximity in three distinct model systems of tumor-immune recognition, leading to significant functional enhancements. Collectively, this work underscores the utility of dual proximal covalent labeling as a potential general strategy to stabilize ternary complexes comprising non-interacting proteins and enforce cell-cell interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.