Lang, Manja and Bufe, Bernd and De Pol, Silvia and Reiser, Oliver and Meyerhof, Wolfgang and Beck-Sickinger, Annette G. (2006) Structural properties of orexins for activation of their receptors. JOURNAL OF PEPTIDE SCIENCE, 12 (4). pp. 258-266. ISSN 1075-2617, 1099-1387
Full text not available from this repository. (Request a copy)Abstract
The closely related neuropeptides orexin A and orexin B mediate their actions, including the regulation of sleep and appetite, by the activation of the orexin 1 and 2 receptors. To elucidate the structural prerequisites for receptor activation and subtype selectivity, we performed multiple amino acid substitutions within the sequence of orexin A and human orexin B-(6-28)-peptide and analyzed their solution structures by CD spectroscopy and their activity at both receptors in Ca2+ mobilization assays. For orexin A, we showed that the basic amino acids within the segment of residues 6-14 were important for the activation of both receptors. Furthermore, we showed that the restriction via disulfide bonds is not required to maintain the active structure of orexin A. The kink region of h orexin B has been shown to be important for Ox(2)R selectivity, which is not mediated by the restriction of the turn structure. Additionally, we showed that no particular secondary structure is required for receptor subtype selectivity. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AMINOCYCLOPROPANE-CARBOXYLIC-ACIDS; PROTEIN-COUPLED RECEPTORS; FEEDING-BEHAVIOR; PEPTIDES; NARCOLEPSY; NEUROPEPTIDE; GENE; ANTAGONISTS; REGULATOR; APPETITE; orexin; hypocretin; structure-activity relationship; CD; beta-aminocyclopropane carboxylic acids |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Oliver Reiser |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Feb 2021 09:20 |
| Last Modified: | 17 Feb 2021 09:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34751 |
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