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.
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Other URL: http://dx.doi.org/10.1002/psc.716
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 Ox₂R 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.
|Institutions:||Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Oliver Reiser|
|Keywords:||orexin • hypocretin • structure-activity relationship • CD • β-aminocyclopropane carboxylic acids|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Owner:||Helge Knüttel (ADMIN)|
|Deposited On:||05 Sep 2006|
|Last Modified:||05 Aug 2009 13:22|