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Title: Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs
Authors: Loo, Shining
Kam, Antony
Li, Binbin
Feng, Nan
Wang, Xiaoliang
Tam, James P.
Keywords: Science::Biological sciences::Biochemistry
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.
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.
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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