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Trityl-glycyl-ϵ-CBO-L-lysine is condensed with L-prolyl-L-valine methyl ester and, after amidification and splitting of the trityl group, glycyl-ϵ-CBO-L-lysyl-L-prolyl-L-valylamide is obtained. This is condensed with ditrityl-L-histidyl-L-phenylalanyl-L-arginyl-L-tryptophane prepared by condensation of ditrityl-L-histidyl-L-phenylalanine with L-arginyl-L-tryptophane methyl ester and saponification. Dicyclohexyl-carbodiimide is used as a condensing agent. After splitting off the trityl groups, the final octapeptide, L-histidyl-L-phenylalanyl-L-arginyl-L-tryptophanyl-glycyl-ϵ-CBO-L-lysyl-L-prolyl-L-valylamide is shown to be optically pure by leucine-aminopeptidase digestion.

The syntheses of a large number of Eledoisin analogues, some of which possess a more potent depressor effect than the original peptide, are described. Whereas the C-terminal moiety of the Eledoisin molecule seems to be responsible for its biological action, its N-terminal moiety can be deeply modified or even left out without considerable decrease of activity. There is apparently no relation between the isoelectric points of these analogous peptides and their biological properties.

N-CBO-L-arginyl-L-arginine is condensed with L-prolyl-L-valine methyl ester and, after splitting of the CBO group, L-arginyl-L-arginyl-L-prolyl-L-valine methyl ester is obtained. This is condensed with N-trityl-glycyl-Nϵ-CBO-L-lysyl-Nϵ-CBO-L-lysine and, after selective splitting of the trityl group, glycyl-Nϵ-CBO-L-lysyl-Nϵ-CBOL- lysyl-L-arginyl-L-arginyl-L-prolyl-L-valine methyl ester is obtained. Condensation of this heptapeptide with N-trityl-glycyl-Nϵ-CBO-L-lysyl-L-prolyl-L-valine yields an endecapeptide, which, after selective splitting of the trityl group, is converted into the trihydrochloride of glycyl-Nϵ-CBO-L-lysyl-L-prolyl-L-valyl-glycyl-Nϵ-CBO-L- lysyl-Nϵ-CBO-L-lysyl-L-arginyl-L-arginyl-L-prolyl-L-valine methyl ester. The identity, the chemical purity and the optical homogeneity of this endecapeptide is evidenced by elementary and amino acid analyses, by chromatography and electrophoresis on paper, and by enzymatic degradation.

A total synthesis of salmon calcitonin is described. The C-terminal nonapeptide amide 24–32 was coupled with the heptapeptide 17–23. The resulting hexadecapeptide amide 17–32 was reacted with the heptapeptide 10–16 to give the tricosapeptide 10–32. This was condensed with the N-terminal nonapeptide 1–9, yielding the protected dotriacontapeptide amide 1–32. After removal of the protective groups and purification by gel-filtration the free peptide obtained exhibited the physical, chemical and biological properties of the natural hormone. Its hypocalcaemic activity (ca. 3500 MRC U/mg) is 20–30 times higher than that of porcine or human calcitonin.

A total synthesis of hog thyrocalcitonin is described. A protected C-terminal tridecapeptide amid (20–32) was coupled with a protected central decapeptide (10–19), and the resulting protected tricosapeptide amide (10–32) was reacted with the N-terminal protected nonapeptide (1–9). After elimination of the protective groups, a free dotriacontapeptide amide was obtained whose physical, chemical and biological behaviour was indistinguishable from that of the natural hormone.

Die Eigenschaften einer Serie von synthetischen Peptiden, die mit Eledoisin strukturell und wirkungsmassig verwandt sind, werden beschrieben.

Six new analogues of Lysine-vasopressin have been synthesized 1 Asp(NH2)4-lysine-vasopressin, Ala4-lysine-vasopressin, Ser4-lysine-vasopressin, Ser5-lysine-vaso-pressin, Val7-lysine-vasopressin and (Nϵ-For-Lys)8-vasopressin. All were prepared by the 3 + 6 scheme. The hexapeptides necessary for the synthesis of the former four were prepared by recurrent synthesis, those utilized for the synthesis of the last two, by condensation of two tripeptides. The analogues substituted in position 4 were found to still possess a significant level of activity, whereas those substituted in positions 5 or 7 were almost inactive. Masking of the ϵ-amino group of lysine in position 8 caused no decrease in the oxytocic activities, but affected, to a different degree, the pressor and the antidiuretic activities.

The preparation of new dipeptides and tripeptides, which are useful intermediates in the synthesis of Eledoisin analogues, is described.

The syntheses of the alkaloids of the ergotoxine-group i.e. ergocristine, α- and β-ergokryptine, and ergocornine, are described. Using starting material with known stereochemistry these syntheses allowed to determine the absolute configurations also at C-2′ and C-12′ in the peptide part, which could not be derived from analytical data. All ergot alkaloids of the peptide type possess the same stereochemical structure.