title: beta-Sulfonamido gonadotropin-releasing hormone analogs: synthesis and evaluation of several parent hormone properties.
abstract: With the aim of producing long-acting analogs of gonadotropin releasing hormone (GnRH), four analogs, containing -X(6) (aa)psi(CH(2)SO(2)NH)-Leu(7) building unit (X(aa)=Gly, Ala, Val or Phe), and a reduced-size analog [Des-Tyr(5)]-GnRH which includes the unit Phe(5)psi(CH(2)SO(2)NH)-Leu(6), and [beta-Ala(6)]-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. [beta-Ala(6)]-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.
authors.affiliation: Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel 76100.
authors.forename: Susanna
authors.initials: S
authors.lastname: Di-Segni
authors.forename: Cesare
authors.initials: C
authors.lastname: Giordano
authors.forename: Shai
authors.initials: S
authors.lastname: Rahimipour
authors.forename: Nurit
authors.initials: N
authors.lastname: Ben-Aroya
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Koch
authors.forename: Mati
authors.initials: M
authors.lastname: Fridkin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004355:Drug Stability; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D013449:Sulfonamides; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone