Beta-sulfonamido gonadotropin-releasing hormone analogs: synthesis and evaluation of several parent hormone properties.

With the aim of producing long-acting analogs of gonadotropin releasing hormone (GnRH), four analogs, containing -X6aa?(CH2SO2NH)-Leu7 building unit (Xaa Gly, Ala, Val or Phe), and a reduced-size analog[Des-Tyr5]-GnRH which includes the unit Phe5?(CH2SO2NH)-Leu6, and [?-Ala6]-GnRH were synthesized. The peptides were evaluated for their capacity to induce LH-release from rat pituitary cells and to withstand proteolysis by pituitary-derived enzymes, compared with the parent peptide GnRH. Albeit stable toward enzymatic degradation, the sulfonamido containing peptides were only marginally bioactive. [?-Ala6]-GnRH, however, induced LH-release and bound to pituitary receptors nearly as efficiently as GnRH. This analog was also highly stable toward proteolysis suggesting that it may serve as a long-acting GnRH-analog.