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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.

Deamino1-Arg8-vasopressin and deamino1-Phe-2Arg8-vasopressin have been synthesized by condensation of L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-G-tosyl-L-arginyl-glycinamide with β-benzylthio-propionyl-L-tyrosyl-L-phenyl-alanylazide and β-benzylthio-propionyl-L-phenylalanyl-L-phenylalanylazide, respectively. After removal of the protecting groups and oxidation with hydrogen peroxide, the deamino-nonapeptides have been purified by counter-current distribution. Deamino1-Arg8-vasopressin as well as deamino1-Phe2-Arg8-vasopressin exhibit a higher antidiuretic activity (1300 IU/mg and 800 IU/mg, respectively) and a lower pressor activity than arginine-vasopressin. This confers to both analogues, and especially to the latter, a remarkable selectivity of the antidiuretic action.

Four analogues of the vasopressins have been synthesised: Deamino1-Orn8-vasopressin, Deamino1-Phe2-Orn8-vasopressin, Deamino1-Ile3-Orn8-vasopressin (= Deamino1-Orn8-oxytocin) and Deamino1-Phe2-Ile3-Orn8-vasopressin (= Deamino1-Phe2-Orn8-oxytocin). The two former have been prepared by condensation of tripeptide azides with an hexapeptide. The two latter have been obtained from the hexapeptide by the recurring method, using active trichlorophenyl esters.

Phe2-Orn8-vasopressin and Phe2-Orn8-oxytocin have been prepared by synthesis Both analogues, but especially the second one, have a more selective pressor activity than the natural vasopressins and than most hitherto synthesized analogues these hormones.

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.

Syntheses of arginine-vasopressin, arginine-vasotocin, and of their deoxy analogues, Phe2-arginine-vasopressin and Phe2-arginine-vasotocin, are described, in which a tosyl group is used for the transitory protection of the guanido group of the arginine residue. Absence of the phenolic hydroxyl group decreases the main biological activities, but in a lower extent than in the corresponding families of oxytocin and lysine-vasopressin.

N-CBO-L-Glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-azide has been condensed with L-prolyl-ϵ-N-tosyl-L-lysyl-glycinamide, giving N-CBO-L-glutaminyl L-asparaginyl-S-benzyl-L-cysteinyl-L-prolylϵ-N-tosyl-L-lysyl-glycinamide, which after spliting of the CBO-protecting group has been condensed with N-CBO-S-benzyl-L-cysteinyl-L-tyrosyl-L-isoleucyl-azide. Cleavage of the protecting groups of the resulting nonapeptide with sodium in liquid ammonia, oxidation with air in dilute aqueous solution and purification by counter-current distribution afforded Lys8-oxytocin, which represents a structural intermediate between oxytocin and lysine-vasopressin and which exhibits the biological properties of both these natural hormones.

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.

Different methods have been investigated for the preparation of N-CBO-S-benzyl- L-cysteinyl-N-methyl-L-tyrosyl-L-isoleucine. Condensation of this protected tripeptide with L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucyl-glycinamide affords N-CBO- S -benzyl-L-cysteinyl-N -methyl-L-tyrosyl-L-isoleucyl-L-glutaminyl-L- asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucyl-glycinamide. Cleavage of the protecting groups of the resulting nonapeptide with sodium in liquid ammonia, oxidation with air in dilute aqueous solution and purification by counter-current distribution gives the desired cyclic nonapeptide amide : (N-methyl-Tyr)2-oxytocin. This exhibits less than one per cent of the oxytocic potency of oxytocin.

Orn8-vasopressin and Orn8-oxytocin have been synthesized and their biological activities compared with those of arginine-vasopressin and lysine-vasopressin and of arginine-vasotocin and lysine-vasotocin, respectively. The replacement of the arginine or lysine residues by an ornithin residue to not considerably affect the oxytocic and pressorie activities.

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.

Hog thyrocalcitonin has been isolated in the form of an homogeneous peptide. After digestion with trypsin three fragments have been separated by paper electrophoresis. the amino acid composition of intact thyrocalcitonin and of the three tryptic fragments is given in a table.

Deamino1-Phenylalanin2-Arginin8-Vasopressin, dessen Synthese und pharmakologische Haupteigenschaften beschrieben werden, zeichnet sich durch eine hohe antidiuretische Wirkung aus. Dieser Effekt ist demjenigen des menschlichen antidiuretischen Hormons qualitativ ahnlich, jedoch wesentlich selektiver.

Eine neue Synthese von Arginin-Vasotocin (= Arg8-Oxytocin = Ile3-Arginin-Vasopressin) wird beschrieben. Das reine synthetische Peptid erwies sich in verschiedenen biologischen Testen wirksamer als nach fruheren Literaturangaben zu erwarten war.

Die Synthese und die pharmakologischen Haupteigenschaften von Orn8-Vasopressin, Phe2-Orn8-Vasopressin, Orn8-Oxytocin und Phe2-Orn8-Oxytocin werden beschrieben. Die pressorische Aktivitat dieser Peptide zeigt eine in der Reihenfolge zunehmende Selektivitat.

Die Synthese und die pharmakologischen Haupteigenschaften von Desamino2-Arginin-Vasopressin werden beschrieben. Dieses Peptid ist durch eine hohe (1300 IE/mg) und relativ selektive antidiuretische Wirksamkeit ausgezeichnet.