Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs
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, cellu...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/156118 |
| _version_ | 1811679846662668288 |
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| author | Loo, Shining Kam, Antony Li, Binbin Feng, Nan Wang, Xiaoliang Tam, James P. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Loo, Shining Kam, Antony Li, Binbin Feng, Nan Wang, Xiaoliang Tam, James P. |
| author_sort | Loo, Shining |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:15:39Z |
| format | Journal Article |
| id | ntu-10356/156118 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:15:39Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1561182023-02-28T17:11:26Z Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs Loo, Shining Kam, Antony Li, Binbin Feng, Nan Wang, Xiaoliang Tam, James P. School of Biological Sciences Science::Biological sciences::Biochemistry Science::Medicine Amino Acid Motifs Epidermal Growth Factor Receptor 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. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version This research was supported in part by the Competitive Research Grant by National Research Foundation in Singapore (NRF-CRP8−2011-05), Nanyang Technological University Internal Funding−Synzyme and Natural Products (SYNC), and the AcRF Tier 3 funding (MOE2016-T3−1-003). 2022-04-06T07:15:14Z 2022-04-06T07:15:14Z 2021 Journal Article 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 0022-2623 https://hdl.handle.net/10356/156118 10.1021/acs.jmedchem.1c00551 11 64 7746 7759 en NRF-CRP8−2011-05 MOE2016-T3−1-003 Journal of Medicinal Chemistry © 2021 The Authors. Published by American Chemical Society. This is an open-access article distributed under the terms of the Creative Commons Attribution License. application/pdf |
| spellingShingle | Science::Biological sciences::Biochemistry Science::Medicine Amino Acid Motifs Epidermal Growth Factor Receptor Loo, Shining Kam, Antony Li, Binbin Feng, Nan Wang, Xiaoliang Tam, James P. Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs |
| title | Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs |
| title_full | Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs |
| title_fullStr | Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs |
| title_full_unstemmed | Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs |
| title_short | Discovery of hyperstable noncanonical plant-derived epidermal growth factor receptor agonist and analogs |
| title_sort | discovery of hyperstable noncanonical plant derived epidermal growth factor receptor agonist and analogs |
| topic | Science::Biological sciences::Biochemistry Science::Medicine Amino Acid Motifs Epidermal Growth Factor Receptor |
| url | https://hdl.handle.net/10356/156118 |
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