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|Title:||Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs||Authors:||Loo, Shining
Tam, James P.
|Issue Date:||2021||Source:||Loo, S., Kam, A., Li, B., Feng, N., Wang, X. & Tam, J. P. (2021). Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs. Journal of Medicinal Chemistry, 64(11), 7746-7759. https://dx.doi.org/10.1021/acs.jmedchem.1c00551||Project:||NRF-CRP8−2011-05
|Journal:||Journal of Medicinal Chemistry||Abstract:||Here, we report the discovery of the first plant- derived and noncanonical epidermal growth factor receptor (EGFR) agonist, the 36-residue bleogen pB1 from Pereskia bleo of the Cactaceae family. We show that bleogen pB1 is a low-affinity EGFR agonist using a suite of chemical, biochemical, cellular, and animal experiments which include incisor eruption and wound- healing mouse models. A focused positional scanning pB1 library of Ala- and D-amino acid scans yielded a high-affinity pB1 analog, [K29k]pB1, with a 60-fold-improved EGFR affinity and mitogenicity. We show that the potency of [K29k]pB1 and the epidermal growth factor (EGF) is comparable in a diabetic mouse wound-healing model. We also show that both bleogen pB1 and [K29k]pB1 are hyperstable, being >100-fold more stable than EGF against proteolytic degradation. Overall, our discovery of a noncanonical proteolytic-resistant EGFR agonist scaffold could open new avenues for developing wound healing and skin regeneration therapeutics and biomaterials.||URI:||https://hdl.handle.net/10356/156118||ISSN:||0022-2623||DOI:||10.1021/acs.jmedchem.1c00551||Schools:||School of Biological Sciences||Rights:||© 2021 The Authors. Published by American Chemical Society. This is an open-access article distributed under the terms of the Creative Commons Attribution License.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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