Yousif, Ali Munaim (2015) Synthesis of New Ligands of Urokinase Receptor and New Urotensin-II Derivatives. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Synthesis of New Ligands of Urokinase Receptor and New Urotensin-II Derivatives
Yousif, Ali
Date: 31 March 2015
Institution: Università degli Studi di Napoli Federico II
Department: Farmacia
Scuola di dottorato: Scienze farmaceutiche
Dottorato: Scienza del farmaco
Ciclo di dottorato: 27
Coordinatore del Corso di dottorato:
D'Auria, Maria
Lubell, William D.UNSPECIFIED
Date: 31 March 2015
Keywords: UII upar peptide chemistry
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/09 - Farmaceutico tecnologico applicativo
Date Deposited: 10 Apr 2015 11:56
Last Modified: 28 Apr 2016 01:00
DOI: 10.6092/UNINA/FEDOA/10547

Collection description

Unit 1: The urokinase-type plasminogen activator receptor (uPAR) is involved in the regulation of cell migration. The uPAR is formed by three domains connected by short linker region. The Ser88-Arg-Ser- Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as result of its binding with formyl peptide receptor (FPRs). With aim to perform a SAR study on this sequence we have synthesized a large peptide library using phosphorylated amino acids, non-coded amino acids, D-amino acid scan and cyclic analogues. A new two potent inhibitors of cell migration, uPAR2 and uPAR18, have been identified represented, respectivetly, by the analogue with phosphorylated Ser90 and the analogue with cyclic conformation. Unit 2: Urotensin II (U-II), is a cyclic peptid has been described as the most potent vasoconstrictor documented. The vasocontriction effect of U-II is a result of the binding with its receptor UT receptor. The cyclic region of U-II, c[Cys-Phe-Trp-Lys-Tyr-Cys], plays an essential role in terms of affinity for UT receptor. We developed new two different libraries of U-II analogues carried structure modification on the peptide bond to explore new SARs on the cyclic region of U-II. Peptoids analogues represent the first library whose the side chain are appended to N-atom rather than the α- Carbon. The second library represented by N-aminosulfamide analogues (azasulfurylpeptides), a class of peptidomimetics, in which the CαH and the carbonyl are respectively replaced by a nitrogen atom and a sulfonyl group.


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