title: Structural investigation of Cetrorelix, a new potent and long-acting LH-RH antagonist.
abstract: The new decapeptide SB-75 (INN: Cetrorelix) has been characterized as a potent antagonist of luteinizing-hormone releasing hormone (LH-RH). Such derivatives are of great medicinal interest owing to their potential application in areas such as hormone-dependent tumors, uterine fibroids, and in diseases and conditions which result from inappropriate hormone levels or which can be treated by suppression of estrogens. SB-75 is the subject of intensive ongoing clinical evaluation and is an accepted standard for the design of new LH-RH antagonists. We characterized SB-75 by means of modern MS and NMR techniques to demonstrate the significance of both sequencing methods on a complicated unnatural decapeptide. Our structural elucidations with nuclear Overhauser (NOE) experiments revealed clear evidence for a highly flexible molecule with no single predominant conformation even in sodium dodecyl sulfate (SDS) mimicking a cellular membrane.
authors.affiliation: Degussa AG, Hanau-Wolfgang, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: E
authors.initials: E
authors.lastname: Busker
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: B
authors.initials: B
authors.lastname: Kutscher
authors.forename: M
authors.initials: M
authors.lastname: Bernd
authors.forename: A V
authors.initials: AV
authors.lastname: Schally
mesh_terms: D000595:Amino Acid Sequence; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011966:Receptors, LHRH / Q000378:metabolism; D012997:Solvents
chemical_list: D011966:Receptors, LHRH; D012997:Solvents; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix