Nouveau polypeptide et son procédé de préparation

The invention comprises the hendecapeptide pyroglutamyl - prolyl - seryl - lysyl - aspartyl alanyl - phenylalanyl - isoleucyl - glycyl leucyl-methionine amide (wherein all the amino acid residues are of L-configuration), its acid addition salts, and peptide having a protective group on the e -amino radical of the lysine residue and, optionally, a protective group on the end amido group of the pyroglutamine residue and/or a protective group on the b -carboxyl radical of the aspartic acid residue, and the preparation thereof by condensing a suitably protected pyroglutamyl-prolyl-seryl-lysine having, optionally, the carboxyl radical of the lysine residue substituted with a radical reactive with amino radicals to form an amide link with aspartyl-alaryl - phenylalanyl - isoleucyl - glycyl - leucyl-methionine amide, optionally protected, and if desired removing the protecting groups in one or more stages. Protecting groups for the pyroglutamyl residue are, for example, carbobenzoxy, carbo-tertiary-butoxy and p-nitrocarbo benzoxy; for the Ne amino group of lysine, the aforementioned together with phthalyl and formyl; and for the b -carboxyl group benzoyl, p-nitrobenzyl, methyl, ethyl, tertiary-butyl and amido radicals. Groups in the tetrapeptide reactive with amino radicals to form amide linkages are azide, and p-nitrophenyl ester radicals; an asymmetric anhydride of the detetrapept or the reaction product of the tetrapeptide with dicyclohexylcarbodiimide. Pyroglutamyl - prolyl - seryl - (Ne - carbotertiary-butoxy) lysine hydrazide is prepared by condensing carbobenzoxypyroglutamine p-nitrophenyl ester with prolin to give carbobenzoxypyroglutamyl-proline, condensing this with seryl - Ne - carbobenzoxylysine methyl ester to give carbobenzoxypyroglutamyl - prolyl - seryl-lysine methyl ester, hydrogenating this to give the free tetra peptide ester, forming the Ne -carbo - t - butoxy - lysine derivative and reacting the ester with hydrazine. Seryl - Ne - carbobenzoxylysine methyl ester is prepared by condensing N-tritylserine with Ne -carbobenzoxylysine methyl ester and detritylating the protected dipeptide. Aspartyl - alanyl - phenylalanyl - isoleucyl-glycyl - leucyl - methioninamide is prepared from carbobenzoxyphenylalamine p-nitrophenyl ester and isoleucine methyl ester through carbo-benzoxyphenylalanyl - isoleucyl methyl ester, carbobenzoxy - o - benzyloxyaspartyl - isoleucine methyl ester, carbo - tert - butoxy - aspartyl-alanyl - phenylalanyl - isoleucine meth