Combining elements from two antagonists of formyl peptide receptor 2 generates more potent peptidomimetic antagonists

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Sarah Line Skovbakke, Andre Holdfeldt, Christina Nielsen, Anna Mette Hansen, Iris Perez-Gassol, Claes Dahlgren, Huamei Forsman, Henrik Franzyk

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.
OriginalsprogEngelsk
TidsskriftJournal of Medicinal Chemistry
Vol/bind60
Udgave nummer16
Sider (fra-til)6991-6997
ISSN0022-2623
DOI
StatusUdgivet - 2017

ID: 182521174