Abstract
Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4-6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Enzyme Activators / pharmacology
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Gelsolin / chemical synthesis
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Gelsolin / pharmacology*
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Humans
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Molecular Structure
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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NADPH Oxidases / metabolism
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Neutrophils / metabolism
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Oligopeptides / pharmacology
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Peptide Fragments / chemical synthesis
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Peptide Fragments / pharmacology*
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Peptides / chemical synthesis
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Peptides / chemistry
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Peptides / pharmacology*
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Peptidomimetics / chemical synthesis
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Peptidomimetics / chemistry
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Peptidomimetics / pharmacology*
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Receptors, Formyl Peptide / antagonists & inhibitors*
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Receptors, Lipoxin / antagonists & inhibitors*
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Signal Transduction / drug effects
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Structure-Activity Relationship
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Superoxides / analysis
Substances
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Enzyme Activators
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FPR2 protein, human
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Gelsolin
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Oligopeptides
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Pam-(Lys-beta-Nspe)6-NH2
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Peptide Fragments
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Peptides
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Peptidomimetics
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Receptors, Formyl Peptide
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Receptors, Lipoxin
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Trp-Lys-Tyr-Met-Val-Met
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gelsolin (160-169)
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Superoxides
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N-Formylmethionine Leucyl-Phenylalanine
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NADPH Oxidases