Title
Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration
Author
Ali Munaim Yousifa, Vincenzo Ingangi, Francesco Merlino, Diego Brancaccio, Michele Minopoli, Rosa Bellavita, Ettore Novellino, Maria Vincenza Carriero, Alfonso Carotenuto, Paolo Grieco
Year
2018
Journal
European Journal of Medicinal Chemistry
Abstract
The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration. We and others have previously documented that the uPAR(84–95) sequence, interacts with the formyl peptide receptors (FPR)s, henceforth inducing cell migration of several cell lines, including leukocytes, and the synthetic shorter peptide (Ser88-Arg-Ser-Arg-Tyr92, SRSRY) retains chemotactic activity in vitro and in vivo. Recently, we have developed the head-to-tail cyclic analog [SRSRY], a new potent and stable inhibitor of monocytetrafficking. This prompted us to develop novel cyclic and linear analogs of [SRSRY] with the aim to broaden the knowledge about structure-activity relationships of peptide [SRSRY]. Herein we report their synthesis, effects on cell migration, conformational and docking analyses which served to envisage a new pharmacophore model for inhibitors of FPR1-triggered cell migration.
Instrument
J-710
Keywords
Circular dichroism, Secondary structure, Membrane interactions, Biochemistry, Medicinal