β-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 -X⁶_aaψ(CH₂SO₂NH -Leu⁷ building unit (X_aa=Gly, Ala, Val or Phe), and a reduced-size analog [Des-Tyr⁵]-GnRH which includes the unit Phe⁵ψ(CH₂SO₂NH)-Leu⁶, and [β-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. [β-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.