Inhibitors of the luteinizing hormone-releasing hormone based upon modifications in the 2, 3, and 6 positions

Abstract

[Leu2,Leu3,D-Ala6]-LH-RH (less than Glu-Leu-Leu-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-[NH2) and [Val2,Leu3,D-Ala6]-LH-RH completely inhibited the release of LH and FSH induced by 0.3 ng/ml of medium of LH-RH on isolated rat pituitaries, at a dosage of 10 mug. [Leu2,Val3,D-Ala6]-LH-RH and [Val2,Val3,D-Ala6]-LH-RH also completely inhibited this response but were one-tenth as active as [Leu2,Leu3,D-Ala6]-LH-RH. All of the analogs were devoid of agonist activities. The incorporation of the D-Ala residue in position 6 into the [Leu2,Leu3]-LH-RH sequence, therefore, increased the inhibition potency as much as tenfold.