ArticleSmall science2026
Engineering a Glucose-Responsive Glucagon Prodrug Through Arginine-Phenylboronic Acid Pendant Modification.
Article in Small science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
1 citing paper in PubMed.
- Engineering a Glucose-Responsive Glucagon Prodrug Through Arginine-Phenylboronic Acid Pendant Modification.Small science · 2026Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activatable prodrug strategies offer powerful means to control therapeutic presentation in space and time. Here, we report a single-molecule prodrug design that enables glucose-responsive activation of a glucagon analog for hypoglycemia protection. The system conjugates dasiglucagon with a synthetic pendant comprised of alternating arginine and phenylboronic acid (PBA) units, designed to couple peptide solubility to glucose concentration. The pendant modulates net charge through glucose-dependent PBA-diol complexation, driving aggregation under normoglycemia and solubilization under hypoglycemia. The lead pendant contains five arginine-PBA repeats and exhibits optimal glucose-responsive solubility and charge modulation, forming aggregates at high glucose and dissolving as glucose levels decline. Despite a modest reduction in receptor potency relative to native dasiglucagon, this approach provides significant prophylactic protection in a streptozotocin-induced diabetic mouse model of insulin overdose, rescuing mice from hypoglycemia and eliminating mortality events. This work demonstrates a proof-of-concept for molecularly engineered, metabolite-responsive glucagon prodrugs that function as on-demand therapeutic depots. More broadly, it establishes a modular design paradigm for dynamic, self-regulating peptide therapeutics based on charge modulation rather than external carrier systems.
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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 OpenQuestion graph.