Characterization of new stable ghrelin analogs with prolonged orexigenic potency
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22182933
DOI
10.1124/jpet.111.185371
PII: S0022-3565(24)46777-3
Knihovny.cz E-resources
- MeSH
- Ghrelin analogs & derivatives chemical synthesis metabolism MeSH
- Molecular Sequence Data MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Eating drug effects MeSH
- Receptors, Ghrelin metabolism MeSH
- Growth Hormone blood MeSH
- Amino Acid Sequence MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ghrelin MeSH
- Receptors, Ghrelin MeSH
- Growth Hormone MeSH
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.
References provided by Crossref.org
Late-stage labeling of diverse peptides and proteins with iodine-125
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High-Fat Diet Induces Resistance to Ghrelin and LEAP2 Peptide Analogs in Mice
