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The lipidated peptidomimetic Lau-[(S)-Aoc]-(Lys-βNphe)6-NH2 is a novel formyl peptide receptor 2 agonist that activates both human and mouse neutrophil NADPH-oxidase.

Författare och institution:
André Holdfeldt (Institutionen för medicin); Sarah Line Skovbakke (-); Malene Winther (Institutionen för medicin); Michael Gabl (Institutionen för medicin); Christina Nielsen (-); Iris Perez-Gassol (-); Camilla Josephine Larsen (-); Ji Ming Wang (-); Anna Karlsson (Institutionen för medicin); Claes Dahlgren (Institutionen för medicin); Huamei Forsman (Institutionen för medicin); Henrik Franzyk (-)
Publicerad i:
The Journal of biological chemistry,
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Neutrophils expressing formyl peptide receptor 2 (FPR2) play key roles in host defense, immune regulation, and in resolution of inflammation. Consequently, the search for FPR2-specific modulators has attracted much attention due to its therapeutic potential. Earlier described agonists for this receptor display potent activity for the human receptor (FPR2) but low activity for the mouse receptor orthologue (Fpr2), rendering them inapplicable in murine models of human disease. Here we describe a novel FPR2 agonist, the proteolytically stable α-peptide/β-peptoid hybrid Lau-[(S)-Aoc]-(Lys-βNphe)6-NH2 (F2M2), showing comparable potency in activating human and mouse neutrophils by inducing a rise in intracellular calcium and assembly of the superoxide-generating NADPH-oxidase. The FPR2/Fpr2 agonist contains a headgroup of 2-aminooctanoic acid (Aoc) residue acylated with lauric acid (C12 fatty acid), which is linked to a peptide/peptoid repeat (Lys-βNphe)6-NH2). Both the fatty acid moiety and the (S)-Aoc residue were required for FPR2/Fpr2 activation. This type of proteolytically stable FPR2-specific peptidomimetics may serve as valuable tools for future analysis of FPR2 signaling as well as for development of prophylactic immunomodulatory therapy. This novel class of cross-species FPR2/Fpr2 agonists should enable translation of results obtained with mouse neutrophils (and disease models) into enhanced understanding of human inflammatory and immune diseases.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Klinisk medicin
Postens nummer:
Posten skapad:
2016-09-02 16:09

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