Discovery of Hyperstable Noncanonical Plant-Derived Epidermal Growth Factor Receptor Agonist and Analogs

Here, we report the discovery of first plant-derived and noncanonical epidermal growth factor receptor (EGFR) agonist, 36-residue bleogen pB1 from Pereskia bleo Cactaceae family. We show that is a low-affinity EGFR agonist using suite chemical, biochemical, cellular, animal experiments which include incisor eruption wound-healing mouse models. A focused positional scanning library Ala- d-amino acid scans yielded high-affinity analog, [K29k]pB1, with 60-fold-improved affinity mitogenicity. potency [K29k]pB1 (EGF) comparable in diabetic model. also both are hyperstable, being >100-fold more stable than EGF against proteolytic degradation. Overall, our proteolytic-resistant scaffold could open new avenues for developing wound healing skin regeneration therapeutics biomaterials.