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Open AccessArticle

Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization

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)
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., 3ae) 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-Text
Keywords: 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 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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MDPI and ACS Style

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. https://doi.org/10.3390/biomedicines6040098

AMA Style

Turcotte S, Mellal K, Chingle R, Mulumba M, Omri S, Dif-Yaiche L, Chemtob S, Ong H, Lubell WD. Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization. Biomedicines. 2018; 6(4):98. https://doi.org/10.3390/biomedicines6040098

Chicago/Turabian Style

Turcotte, Stéphane; Mellal, Katia; Chingle, Ramesh; Mulumba, Mukandila; Omri, Samy; Dif-Yaiche, Lylia; Chemtob, Sylvain; Ong, Huy; Lubell, William D. 2018. "Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization" Biomedicines 6, no. 4: 98. https://doi.org/10.3390/biomedicines6040098

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