Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization
Stéphane Turcotte 1,†
, Katia Mellal 2,†, Ramesh Chingle 1, Mukandila Mulumba 2, Samy Omri 3, Lylia Dif-Yaiche 1, Sylvain Chemtob 3,4, Huy Ong 2 and William D. Lubell 1,*
, Katia Mellal 2,†, Ramesh Chingle 1, Mukandila Mulumba 2, Samy Omri 3, Lylia Dif-Yaiche 1, Sylvain Chemtob 3,4, Huy Ong 2 and William D. Lubell 1,*
1
Departments of Chemistry, Université de Montréal, Montréal, QC H3C 3J7, Canada
2
Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada
3
Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, Canada
4
Pediatrics, Ophthalmology and Pharmacology, Université de Montréal, Montréal, QC H3C 3J7, Canada
*
Author to whom correspondence should be addressed.
†
These authors contribute equally to this work.
Biomedicines 2018, 6(4), 98; https://doi.org/10.3390/biomedicines6040098
Received: 28 August 2018 / Revised: 26 September 2018 / Accepted: 5 October 2018 / Published: 22 October 2018
(This article belongs to the Special Issue Discovery and Development of Constrained Peptide Ligands)
Abstract
Modulation of the cluster of differentiation-36 receptor (CD36) has proven promising for dampening pro-inflammatory macrophage signaling. For example, azapeptides (e.g., 1 and 2) bind CD36 selectively with high affinity, mitigate Toll-like receptor (TLR) agonist-induced overproduction of nitric oxide (NO), and reduce pro-inflammatory cytokine and chemokine production in macrophages. Moreover, semicarbazides 1 and 2 inhibit microvascular sprouting mediated through CD36 in the choroid explant. Seeking a selective CD36 modulator that mediated inflammation without influencing neovascularization, a set of azasulfurylpeptides (e.g., 3a–e) were synthesized in which the semicarbazide was replaced by an N-aminosulfamide residue using a novel solid-phase approach. Notably, azasulfurylpeptide 3c diminished selectively CD36-mediated TLR-2-triggered inflammatory response without affecting neovascularization. Subtle chemical modification at the peptide backbone from a carbonyl to a sulfuryl residue has had a selective effect on biological activity providing a valuable probe for studying CD36 chemical biology. View Full-TextKeywords:
age-related macular degeneration; azapeptide; azasulfurylpeptide; cluster of differentiation 36; fibroblast-stimulating lipopeptide; growth hormone-releasing peptide-6; N-Aminosulfamide; nitric oxide; semicarbazide; toll-like receptor; tumor necrosis factor-α
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Turcotte, S.; Mellal, K.; Chingle, R.; Mulumba, M.; Omri, S.; Dif-Yaiche, L.; Chemtob, S.; Ong, H.; Lubell, W.D. Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization. Biomedicines 2018, 6, 98.
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