Ghrelin Receptor Ligands: Design and Synthesis of Pseudopeptides and Peptidomimetics

ISSN: 1872-3136 (Online)
ISSN: 2212-7968 (Print)


Volume 8, 3 Issues, 2014


Download PDF Flyer




Current Chemical Biology

Aims & ScopeAbstracted/Indexed in


Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK
Email: ccb@benthamscience.org

View Full Editorial Board

Subscribe Purchase Articles Order Reprints


Ghrelin Receptor Ligands: Design and Synthesis of Pseudopeptides and Peptidomimetics

Author(s): Aline Moulin, Luc Brunel, Pascal Verdie, Laurent Gavara, Jean Martinez and Jean-Alain Fehrentz

Affiliation: Institut des Biomolecules Max Mousseron, UMR 5247, CNRS-Universites Montpellier 1-Montpellier 2, Faculte de Pharmacie, 15 avenue Charles Flahault, B.P. 14491, 34093 Montpellier, France.

Abstract

Mainly synthesized in the stomach, ghrelin is a peptide hormone which stimulates growth hormone secretion and appetite, thus promoting food intake and body-weight gain. Historically, researchers started to work on the discovery of ghrelin receptor ligands several years before the discovery of the ghrelin receptor and the hormone itself. Indeed peptides able to stimulate growth hormone secretion (growth hormone releasing peptides, GHRPs) were found while the mechanism of action and the target receptor were still unknown. Non peptidic agonists were then described (growth hormone secretagogues, GHSs) and the receptor (GHS-R1a) identified in 1996. Three years later, the natural ligand of this receptor (ghrelin) was isolated from stomach and its chemical synthesis allowed to show the physiological role of ghrelin in energy balance. In this review, we present some pseudopeptide and peptidomimetic approaches used by researchers for the design of ghrelin receptor ligands. We will start by the pioneering work of Bowers et al. on enkephalin analogues, which was the starting point for the development of an impressive number of compounds, by several of the major worldwide pharma companies. We will also describe the work achieved starting from a substance P derivative, which was one of the first peptides identified as an antagonist of the newly discovered ghrelin receptor. Then we will review the structure activity relationship study starting from the peptide ghrelin, which started with the discovery of this peptide in 1999. We will also focus on a more recent work based on macrocyclic peptidic analogues for the development of ghrelin receptor ligands.

Keywords: Ghrelin, growth hormone, obesity.

Purchase Online Rights and Permissions

Article Details

Volume: 7
Issue Number: 3
First Page: 254
Last Page: 270
Page Count: 17
DOI: 10.2174/2212796807999131128125920
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science