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 monocyte trafficking. 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.

Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration / Yousif, Ali Munaim; Ingangi, Vincenzo; Merlino, Francesco; Brancaccio, Diego; Minopoli, Michele; Bellavita, Rosa; Novellino, Ettore; Carriero, Maria Vincenza; Carotenuto, Alfonso; Grieco, Paolo. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 143:(2018), pp. 348-360. [10.1016/j.ejmech.2017.11.030]

Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration

Yousif, Ali Munaim;Merlino, Francesco;Brancaccio, Diego;BELLAVITA, ROSA;Novellino, Ettore;Carotenuto, Alfonso
;
Grieco, Paolo
2018

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 monocyte trafficking. 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.
2018
Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration / Yousif, Ali Munaim; Ingangi, Vincenzo; Merlino, Francesco; Brancaccio, Diego; Minopoli, Michele; Bellavita, Rosa; Novellino, Ettore; Carriero, Maria Vincenza; Carotenuto, Alfonso; Grieco, Paolo. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 143:(2018), pp. 348-360. [10.1016/j.ejmech.2017.11.030]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/701474
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