Synthesis and biological activity of alpha-azapeptides: alpha-aza-analogues of luteinizing hormone releasing hormone.

The term "alpha-azapeptides" is applied to analogues derived by change of one or more of the alpha-CHs of amino-acid residues in peptides by N; in such analogues the overall polarity of the molecule and the spacing of side-chain residues is preserved, but stability towards peptidases may be increased because of the changed conformational situation at the residue or residues involved in the change. Three alpha-aza-analogues of LHRH, i.e. azaglycine6-, azalanine6-, and azaglycine10-LHRH, and two alpha-aza-analogues, of des-His-LHRH, i.e. azaglycine6- and azalanine3-des-His-LHRH, were prepared. The three alpha-aza-analogues of LHRH were as active as LHRH in inducing ovulation in androgen-sterilized, constant-oestrus rats, but less potent than LHRH in causing LH release in immature male rats. Evidence of increased duration of action was not obtained. The two aza-analogues of des-His-LHRH were neither agonists nor antagonists in these two test systems.