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E Wünsch

Publications and source records attributed to E Wünsch.

At least 73 records · Page 4Linked to original sources
PubMed1982

(Alkyldithio)carbonyl groups for protection of amino functions in peptide synthesis.

(Alkyldithio)carbonyl groups were examined for their usefulness as amino-protecting groups in peptide chemistry. Among the derivatives studied, the (cyclohexyldithio)carbonyl function was found to be the most suitable for practical application. The related amino acid derivatives are obtained by relatively simple procedures and are sufficiently stable under normal conditions of peptide synthesis. Reductive cleavage with thiols or phosphines results in quantitative removal of this new amino protecting group.U

Acylation↗
PubMed1982

A new method for the selective synthesis of unsymmetrical cystine peptides.

A convenient method for the synthesis of unsymmetrical cystine peptides is described, which is based on the conversion of one cysteine component to the corresponding sulfenohydrazide by reaction with azodicarboxylic acid derivatives. Following the isolation and characterization of this S-activated intermediate, its thiolysis via the second cysteine component leads to the desired disulfide bridging.

Cysteine↗
PubMed1982

Biological and immunological properties of human gastrin I analogues.

The 15-methionine of human little gastrin I, prone to oxidation with concomitant loss of biological activity, has been replaced by leucine, norleucine and methoxinine, respectively. The resulting analogues exhibit acid secretory potencies practically undistinguishable from that of the parent hormone, whereas their immunoreactivity, as assayed with four different antisera raised against human little gastrin I, reflect to a significant extent the afforded modifications. Only [15-methoxinine]human little gastrin I retains practically the full reactivity for all antisera examined. The results suggest that this 15-methoxinine analogue is well suited for both biological and immunological studies.

Animals↗
PubMed1981

Secretin binding sites coupled with adenylate cyclase in rat fundic membranes.

Specific binding sites for secretin have been identified in rat fundic membranes, using 125I-secretin. The binding was saturable, reversible, time and temperature dependent. Optimal pH for binding was around 7-7.5. Scatchard plots were compatible with the existence of 2 classes of receptors; the first class with a high affinity for secretin (apparent Kd of 4 x 10(-10) M) and a low binding capacity (150 fmol per mg membrane protein, i.e., 4,500 high affinity sites/cell) and a class of receptors with a lower affinity (Kd of 3 x 10(-9) M) and a higher binding capacity (580 fmol per mg membrane protein i.e., 17,400 sites/cell). Glucagon, gastric inhibitory polypeptide and somatostatin had no-effect on secretin binding. In contrast, VIP inhibited 125I-secretin binding and stimulated adenylate cyclase activity, in both cases at a 200-times lower potency than secretin (ID50 and Ka = 2 x 10(-7) M VIP). The properties of these secretin receptors strongly support the concept that secretin acts as a regulatory peptide on the rat gastric epithelium.

Adenylyl Cyclases↗
PubMed1981

In vivo effect of 13 Leu motilin on the electric activity of the rabbit sphincter of Oddi.

Myoelectrical activity of the sphincter of Oddi was studied in 15 anaesthetized and laparotomized male rabbits, before and after injection of various doses of 13 Leucine Motilin (13 L Motilin), a biological and structural analogue of natural motilin. It can be concluded that 13 L Motilin provoked an increase of the sphincter of Oddi spike activity with doses ranging from 0.1 to 1.6 x 10(-6) g/kg. This effect had begun one minute after the injection, reached its maximum at the second minute and lasted for fifteen minutes. The action of 13 L Motilin is dose-related between 0.2 and 0.6 x 10(-6).

Ampulla of Vater↗
PubMed1981

Hydrokinetic activity of secretion and secretin analogues, modified in the N-terminal sequence, and of vasoactive intestinal peptide in the dog pancreas.

In the dog pancreas in vivo, the biological activity of secretin and vasoactive intestinal peptide was compared to that of secretin analogues modified in their N-terminal hexapeptide and to X-secretion (alpha, beta-Asp3-secretin) and Y-secretin (a conversion product of X-secretin consisting of about 15% secretin and 85% beta-Asp3-secretin). Replacement of Asp3 by glutamic acid reduced secretin activity markedly. Replacement by neutral amino acids abolished the activity nearly completely. alpha, beta-Asp3-secretin and beta-Asp3-secretin appeared to be ineffective. The results indicate that the free beta-carboxy group of the side chain of the Asp3 residue of the secretin molecule is of decisive importance for hydrokinetic action.

Amino Acid Sequence↗
PubMed1981

[Total synthesis of somatostatin-28 (author's transl)].

The total synthesis of the octacosapeptide corresponding to the proposed primary structure of porcine somatostatin-28 is described. The synthesis has been performed using a protection scheme of maximum selectivity (acid labile side chain protection based on tert-butyl alcohol and 1-adamantol derived protecting groups in combination with the S-tert-butylthio group for reversible and selective blocking of the cysteine thiol functions and the 2-nitrophenylthio group for the temporary protection of the alpha-amino functions of intermediate segments) and of carefully selected fragments. Upon assembly in sequence order of the four suitably protected fragments related to sequences 18-28, 15-17, 8-14 and 1-7, the asymmetric disulfides were reduced by exposure of the fully protected octacosapeptide to phosphines. Subsequently, the final deprotection was performed with trifluoroacetic acid and the resulting dihydrosomatostatin-28 was then converted by air oxidation into the "cyclic peptide". Gel filtration on Biogel P-6 and ion-exchange chromatography on Biogel CM-2 produced somatostatin-28 at a high degree of purity. Comparative analysis of the synthetic and natural product by means of chromatographic, immunological and biological assays confirmed the structure proposed for this putative precursor of somatostatin-14.

Amino Acid Sequence↗
PubMed1981

[Total synthesis of human big gastrin I. Revised primary structure (author's transl)].

The synthesis of the tetratriacontapeptide amide corresponding to the revised structure of human big gastrin I is described. The fully protected peptide derivative was obtained by assembly in sequence order of the suitably protected fragments [1--9], [10--14] and [15--34] via the dicyclohexylcarbodiimide/N-hydroxysuccinimide and azide method, respectively. Upon removal of the protecting groups by exposure to trifluoroacetic acid and purification of the resulting crude product by chromatographic methods, human big gastrin I was obtained in satisfactory yields and at a high degree of purity. The identical immunological crossreactivities of natural and synthetic human big gastrin I using anti-porcine big gastrin I antiserum strongly supports the correctness of the newly proposed primary structure of this member of the gastrin family.

Amino Acid Sequence↗
PubMed1981

[Studies on the total synthesis of cholecystokinin-pancreozymin. Synthesis of the suitably protected fragment corresponding to the sequence 24--33 (author's transl)].

The synthesis is described of a suitably protected decapeptide derivative corresponding to the C-terminal tyrosin-O-sulfate-containing sequence 24--33 of cholecystokinin-pancreozymin as key fragment for the total synthesis of this gastrointestinal hormone or its 39-variant. This peptide derivative has been prepared according to our newly developed procedure based on the direct use of N-acyltyrosine-O-sulfate barium salt. Additionally, removal of the protecting groups followed by purification via chromatographic methods produced the decapeptide amide in good yields and with a high degree of purity as a fully active cholecystokinin-pancreozymin related peptide.

Cholecystokinin↗
PubMed1981

[Cholecystokinin-pancreozymin synthesis. Synthesis of [28-threonine,31-norleucine]- and [28-threonine,31-leucine]cholecystokinin-pancreozymin-(25-33)-nonapeptide].

The syntheses of two analogues related to the C-terminal nonapeptide amide sequence 25-33 of cholecystokinin-pankreozymin are described. Based on the primary structure of the CCK-PZ-active caerulein and the experiences gained from the methionine replacement with leucine or norleucine in human little gastrin I, the analogues were designed by substituting methionine 28 with threonine, and methionine 31 with leucine and norleucine, respectively. Using a new method for the synthesis of tyrosine-O-sulfate-containing peptides, developed in our laboratory, and applying acid-labile side-chain protection in combination with the benzyloxycarbonyl group, the fully protected nonapeptide amide derivatives Z-Arg(Z2)-Asp(OBut)-Tyr-(SO3Ba1/2)-Thr(But)-Gly-Trp-Leu-Asp(OBut)-Phe-NH2 and Z-Arg(Z2)-Asp(OBut)-Tyr(SO3-Ba1/2)-Thr(But)-Gly-Trp-Nle-Asp(OBut)-Phe-NH2, were obtained. Upon hydrogenolytic and subsequent acidolytic removal of the protecting groups, followed by purification via chromatographic procedures the nonapeptide amides were isolated in satisfactory yields at a high degree of purity. In vivo and in vitro assays showed that a substitution of methionine 31 by norleucine with concomitant replacement of methionine 28 by threonine produced a fully active analogue, whereas for the threonine 28, leucine 31 analogue the pankreozymin-activity was lowered by a factor 10.

Amino Acid Sequence↗
PubMed1980

Evidence for a cyclic AMP system highly sensitive to secretin in gastric glands isolated from the rat fundus and antrum.

The effects of secretin and vasointestinal peptide (VIP) on the production of cyclic AMP have been studied in gastric glands isolated by means of EDTA from rat fundic and antral mucosa. (1) In gastric fundus, secretin and VIP caused a time- and temperature-dependent stimulation of cyclic AMP production that was maximal when the test agents were incubated for 60 min at 20 degrees C in the presence of 0.5 mM 3-isobutyl-1-methylxanthine as a phosphodiesterase inhibitor. The dose-response curve was monophasic for both peptides, the production of cyclic AMP being sensitive to 10(-10) M secretin and to 5 . 10(-8) M VIP. Half-maximal stimulation was obtained with 2.9 10(-9) M secretin or 2 . 10(-7) M VIP and the maximal stimulation represented a 21-fold and a 19-fold increase above control for secretin and VIP, respectively. Histamine also stimulated cyclic AMP production, with a Km of about 5 . 10(-4) M. No additive effect on cyclic AMP production was oberved when secretin and VIP were simultaneously added at maximally active concentrations, while an additive effect was observed when secretin and histamine were added together. (2) In gastric antrum, the characteristics of the secretin- and VIP-stimulated cyclic AMP production were similar to those observed in gastric fundus. Histamine nevertheless failed to stimulate the formation of cyclic AMP in antral mucosa. (3) These data demonstrate the existence of a cyclic AMP system highly sensitive to secretin in gastric glands isolated from the rat fundus and antrum and suggest that VIP operates through this system. (4) It is proposed that the pepsinogen- and/or mucous-secreting cells are implicated in the regulation of cyclic AMP production by secretin in gastric glands of the rat.

Animals↗
PubMed1980

Comparison of biological activity and disappearance rates of synthetic big gastrin, little gastrin and minigastrin in the dog.

Three synthetic preparations of big gastrin (G-34), little gastrin (G-17) and minigastrin (G-14) have been compared with regard to gastric acid stimulatory potency, rate of disappearance and the relation between acid secretion and the change in serum immunoreactive gastrin in gastric fistula and Heidenhain pouch dogs. Equimolar graded doses (12.5 to 200 pmol/kg-hr) of G-14, G-17 and G-34 produced similar rates of acid secretion with equal ED50 for all three gastrin peptides. Equimolar doses of G-14 and G-17 also resulted in similar increments in serum immunoreactive gastrin, but those of G-34 caused approximately two to three times greater increments in serum gastrin than did G-14 or G-17. The disappearance half-times determined by measuring serum gastrin at short intervals after discontinuation of equimolar dose (1000 pmol/kg-hr) infusions of each gastrin peptide were 1.75, 4.85 and 11.53 min for G-14, G-17 and G-34, respectively. The calculated space of distribution was similar for all three gastrin preparations and ranged from 20-30% body weight. These results indicate that the three major gastrin components differ in half-times and in relating secretory potency, in that relatively higher molar concentrations of G-34 than G-14 or G-17 were required to produce equal rates of acid secretion.

Animals↗