STRUCTURAL INVESTIGATION OF CETRORELIX, A NEW POTENT AND LONG-ACTING LH-RH ANTAGONIST

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 potent ial application in areas such as hormone-dependent tumors, uterine fib roids, 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 characte rized SB-75 by means of modern MS and NMR techniques to demonstrate th e significance of both sequencing methods on a complicated unnatural d ecapeptide. Our structural elucidations with nuclear Overhauser (NOE) experiments revealed clear evidence for a highly flexible molecule wit h no single predominant conformation even in sodium dodecyl sulfate (S DS) mimicking a cellular membrane. (C) Munksgaard 1994.