Turn-Adopting Peptidomimetic\nas a Formyl Peptide Receptor‑1\nAntagonist

The design, synthesis, and characterization of a new\npeptidomimetic\nacting as a formyl peptide receptor (FPR1) antagonist (N-19004) are\nherein reported. The molecule has been identified with docking studies\nof the highly potent FPR1 antagonist UPARANT on human receptor. N-19004\nrecapitulates all pharmacophoric groups necessary for recognition\ninto a minimal structure, with a crucial role of the 2,6-diamino-thiophenyl\nscaffold mimicking the positions of Cα atoms of Arg residues\nin the turned Arg-Aib-Arg segment of UPARANT. N-19004 demonstrated to interfere with the biological properties of FPR1 both <i>in vitro</i> and <i>in vivo</i>. In a mouse model\nof choroidal neovascularization, N-19004 markedly reduced the size\nof laser-induced choroidal lesions, with reabsorption of the edema\nregions by a systemic administration route.