Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) High metabolic in vivo stability and bioavailability of a palmitoylated ghrelin receptor ligand assessed by mass spectrometry
Autor Kostelnik, K.B.; Els-Heindl, S.; Klöting, N.; Baumann, S.; von Bergen, M.; Beck-Sickinger, A.G.;
Journal / Serie Bioorganic & Medicinal Chemistry
Erscheinungsjahr 2015
Department METABOX; PROTEOM;
Band/Volume 23
Heft 14
Sprache englisch;
POF III (gesamt) F11;
Keywords Ghrelin receptor; Inverse agonist; Metabolic stability; Mass spectrometry; Stable isotopic labeling
UFZ Querschnittsthemen RU3;
Abstract The constitutive activity of the ghrelin receptor is of high physiological and pathophysiological relevance. In-depth structure-activity relationship studies revealed a palmitoylated ghrelin receptor ligand that displays an in vitro binding affinity in the low nanomolar range. Activity studies revealed inverse agonistic as well as antagonistic properties and in vitro metabolic analysis indicated a high stability in blood serum and liver homogenate. For metabolic testing in vivo, a combined approach of stable isotopic labeling and mass spectrometry-based analysis was established. Therefore, a heavy isotopic version of the peptide containing a 13C-labeled palmitic acid was synthesized and a 1:1 ratio of a 12C/13C-peptide mixture was injected into rats. Biological samples were analyzed by multiple reaction monitoring allowing simultaneous peptide detection and quantification. Measurements revealed a suitable bioavailability over 24 h in rat serum and subsequent high-resolution mass spectrometry investigations showed only negligible degradation and slow body clearance. Hence, this method combination allowed the identification and evaluation of a highly potent and metabolically stable ghrelin receptor ligand in vivo.
ID 15632
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=15632
Kostelnik, K.B., Els-Heindl, S., Klöting, N., Baumann, S., von Bergen, M., Beck-Sickinger, A.G. (2015):
High metabolic in vivo stability and bioavailability of a palmitoylated ghrelin receptor ligand assessed by mass spectrometry
Bioorg. Med. Chem. 23 (14), 3925 - 3932