POLYPEPTIDES .15. SYNTHESIS AND BIOLOGICAL-ACTIVITY OF ALPHA-AZA-ANALOGS OF LULIBERIN MODIFIED IN POSITIONS-6 AND POSITION-10

Analogs of luliberin (luteinizing hormone-releasing hormone) and 2-dehistidyl-luliberin containing .alpha.-aza-Gly [Azgly] (-NHNHCO-) or .alpha.-aza-Ala [Azala] (-NHNMeCO-) residues in either position 6 or 10 were synthesized by classical procedures of peptide synthesis. The agonist and antagonist activities of these compounds were evaluated in androgen-sterilized constant-estrus rats; [10-Azgly]-, [6-Azgly]-, and [6-Azala]-luliberin were marginally less active than the parent peptide. When the aza-change in position 6 was combined with an ethylamide substitution in position 10, the resulting compounds, [6-Azgly-10-de-Gly-NH2-9-Pro-ethylamide]- and [6-Azala-10-de-Gly-NH2-9-Pro-ethylamide]-luliberin, were twice as active as luliberin. [6-D-Ala-10-Azgly]-luliberin was also twice as active as luliberin. [2-de-His-10-Azgly]-luliberin inhibited completely ovulation induced by luliberin (0.5 .mu.g/rat) at a dose of 250 .mu.g/rat, but 2-de-His-analogs of all the other compounds were devoid of antagonist activity in this test system.