1. Combining Elements from Two Antagonists of Formyl Peptide Receptor 2 Generates More Potent Peptidomimetic Antagonists
- Author
-
Henrik Franzyk, Iris Perez-Gassol, Huamei Forsman, Sarah Line Skovbakke, Christina Nielsen, Claes Dahlgren, Anna Mette Hansen, and André Holdfeldt
- Subjects
0301 basic medicine ,Peptidomimetic ,Stereochemistry ,Neutrophils ,Enzyme Activators ,Peptide ,Subclass ,Formyl peptide receptor 2 ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,Superoxides ,Drug Discovery ,Structure–activity relationship ,Humans ,Receptors, Lipoxin ,Receptor ,Gelsolin ,chemistry.chemical_classification ,Molecular Structure ,Antagonist ,NADPH Oxidases ,Combinatorial chemistry ,Receptors, Formyl Peptide ,Peptide Fragments ,N-Formylmethionine Leucyl-Phenylalanine ,030104 developmental biology ,chemistry ,Molecular Medicine ,Peptidomimetics ,Peptides ,Oligopeptides ,030217 neurology & neurosurgery ,Signal Transduction - 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.
- Published
- 2017