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The C-terminal octapeptide of cholecystokinin-pancreozymin and its analogues in which the methionine residues were successively replaced by methoxinine have been synthesized. When these analogues were tested for their gallbladder-contraction activity in an in vitro system the following relative potencies were observed: [Mox3]-CCK-PZ 8 (95%), [Mox6]-CCK-PZ 8 (5%) and [Mox3, Mox6]-CCK-PZ 8 (2%).

Ammonolysis of nitroarginine-containing peptides leads to the formation of ornithine-containing side products. The structure of these side products has been deduced from model experiments. This side reaction can be avoided by using the NG-tosyl or the NG-dicarbobenzoxy protecting groups.

The open linear decapeptide corresponding to one of the four proposed structures (7α) for polymyxin B1, having throughout α-amino peptide bonds, has been synthesized. Attempts to cyclise it to the polymyxin B1 7α isomer by the carbodiimide procedure have not yet been successful.

Synthetic arginine-vasopressin, obtained using the tosyl group for protection of the guanidino group of the arginine residue, has been carefully compared with the freshly isolated natural hormone by physico-chemical and biological methods. Both products proved to be identical.

The syntheses of seven tripeptide isomers containing L-histidine, L-proline and L-glutamic acid residues, the same as found in the natural thyrotropin-releasing hormone (TRH), are reported. In addition L-pyroglutamyl-L-histidyl-L-proline and its amide as well as Nα-acetyl-L-glutamyl-L-histidyl-L-proline are described. Whereas eight peptides are inactive and L-pyroglutamyl-L-histidyl-L-proline shows a slight TRH activity, L-pyroglutamyl-L-histidyl-L-proline-amide has the full biological activity of the isolated thyrotropin-releasing hormone and, at the present state of knowledge, seems to be identical with it.

The isolation and amino acid sequence of substance P from horse intestine is reported. The sequence, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 is identical with the sequence reported for substance P isolated from bovine hypothalami.

The protected open decapeptide XIII, related to one of the four possible structures for polymyxin B1 has been synthesized by condensing together the pentapeptides 1-2-3-4-5 and 1′-2′-6-7-8 using either the azide method or the carbodiimide procedure.

The synthesis of the cycloheptapeptide 7α (Fig. 4) containing the α,γ-diaminobutyric acid residues only in the L form, and its cristallization as pentaphosphate are reported. This latter substance proved to be in all respects identical with the cristalline penta- phosphate of natural polymyxine B1.

Dab1-Dab9-bradykinin (Dab-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Dab) has been prepared by a new procedure which differs from known syntheses of bradykinin. Against carboxypeptidase and chymotrypsin this synthetic analogue of bradykinin behaves in a way similar to that of the natural hormone, but it does not exhibit any pharmacological activity on the isolated rat uterus.

In order to elucidate the structure of natural polymyxin B1 the cyclic decapeptide 8 γ(V, Fig. 3, with 8 amino acids in the ring and the side chain attached in γ-position) has been synthesized. This is one of the four possible structures deduced for the natural product by the usual degradation methods. The cyclic decapeptide 8 γ appears not to be identical with polymyxin B1 in view of its reduced antibacterial activity and different optical rotatory power.

The structure proposed for Evolidine, a cyclic heptapeptide isolated from the leaves of Evodia xanthoxyloides, is confirmed by degradation of the natural product and by synthesis.

The synthesis of an antibiotic substance to which we assign the structure 7α, one of the four possible formulas proposed for natural polymyxin B1, is reported. Although both synthetic and the natural product have the same antimicrobial activity towards Brucella bronchiseptica in vitro (plate test), they are not identical, as shown by the lower optical rotation of the synthetic material.

The synthesis of all-D-Val5-Angiotensin II-Asp1-β-Amide (Scheme 2), the antipode of the active principle of Hypertensin CIBA®, is carried out according to known schemes in the L-series. It showed neither inhibitory nor angiotensin-like effects up to concentrations of 10−3.

Based on our recent observation that as much as 81 % of the weight of the molecule of ovine TRF could be accounted for, following 6N HC1 hydrolysis, by the presence of His, Pro, Glu in equimolar ratio, tripeptide isomers containing His, Pro, Glu were synthesized. The tripeptides proved to be devoid of TRF activity. Following treatment of the tripeptides by acetic anhydride in an effort to protect the N-terminus as in natural TRF, only the acetylation mixture of H-Glu-His-Pro-OH showed biological activity qualitatively indistinguishable from that of natural TRF in in vivo and in vitroassays specific for TRF. The major product byweight of this acetylation procedure was shownto be PCA-His-Pro-OH (PCA is the abbreviationfor 2-pyrrolidone-5-carboxylic acid). PCAHis-Pro-OH isolated from the acetylation mixtureor prepared by total synthesis proved tohave TRF activity (10 U/mg, M.E.D. 10 μg/animal). N-acetyl-Glu-His-Pro-OH obtained bytotal synthesis had no TRF activity when injectedup to 250 μg/animal. Treatment ...

Es wird uber die Synthese von 1-Deamino-bradykinin, 9-Decarboxy-bradykinin und 1-Deamino-9-decarboxy-bradykinin und uber deren biologische Aktivitat berichtet. Nach dem verwendeten Testsystem scheint die endstandige Carboxylgruppe fur die Aktivitat bedeutsamer zu sein als die endstandige Aminogruppe.