Characterization of New Stable Ghrelin Analogs with Prolonged Orexigenic Potency

0376293 - ÚOCHB 2013 RIV US eng J - Článek v odborném periodiku
Maletínská, Lenka - Pýchová, Miroslava - Holubová, Martina - Blechová, Miroslava - Demianova, Zuzana - Elbert, Tomáš - Železná, Blanka
Characterization of New Stable Ghrelin Analogs with Prolonged Orexigenic Potency.
Journal of Pharmacology and Experimental Therapeutics. Roč. 340, č. 3 (2012), s. 781-786. ISSN 0022-3565. E-ISSN 1521-0103
Grant CEP: GA ČR GA303/09/0744
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: ghrelin agonist * cyclohexylalanine * diaminopropionic acid * GHS-R1a
Kód oboru RIV: CE - Biochemie
Impakt faktor: 3.891, rok: 2012

Ghrelin, the only known peripherally produced and centrally acting peptide that stimulates food intake, is synthesized primarily in the stomach and acts through the growth hormone secretagogue receptor (GHS-R1a). In addition to its orexigenic effect, ghrelin stimulates the release of growth hormone (GH). In this study, we investigated the biological properties of full-length and shortened ghrelin analogs in which octanoylated Ser(3) is replaced with an octanoic acid moiety coupled to diaminopropionic acid (Dpr). Ghrelin analogs stabilized with Dpr(N-octanoyl) in position 3 and noncoded amino acids in position 1 (sarcosine) and/or position 4 (naphthylalanine or cyclohexylalanine) were found to possess affinities similar to those of ghrelin for cell membranes with transfected GHS-R1a. In vivo, the prolonged orexigenic effects of analogs containing Dpr(N-octanoyl) 3 compared with that of ghrelin in adult mice and a similar impact on GH secretion in young mice were found. Full-length [Dpr(N-octanoyl)(3)]ghrelin and its analogs with a noncoded amino acid in position 1 and/or 4 showed significantly prolonged stability in blood plasma compared with that of ghrelin. Ghrelin analogs with a prolonged orexigenic effect are potential treatments for GH deficiency or cachexia that accompanies chronic diseases. Desoctanoylated ghrelin analogs and N-terminal penta-and octapeptides of ghrelin did not show any biological activity.
Trvalý link: http://hdl.handle.net/11104/0208735