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Biomedical subjects

L Moroder

Publications and source records attributed to L Moroder.

At least 145 records · Page 8Linked to original sources
PubMed1984

Exocrine pancreatic secretion in response to a new CCK-analog, CCK33 and caerulein in dogs.

We studied the relative molar potencies of a newly synthetized cholecystokinin nonapeptide [Thr28,Nle31]CCK[25-33], natural porcine CCK33 and synthetic caerulein in conscious dogs with chronic gastric and pancreatic fistulas. Peptides were dissolved in albumin-containing solutions to prevent loss from solution. The three peptides were found to be equipotent on a molar basis in stimulating exocrine pancreatic secretion. As [Thr28,Nle31]CCK9 is a peptide less susceptible to oxidation than other forms of CCK, it is an interesting analog with many uses for medical and biological research.

Animals↗
PubMed1984

[Synthesis of peptides with gastrinlike activity. Studies on the structure-activity relationship of the natural hormone human little gastrin I].

To identify the role of the block of glutamic acid residues characteristic for the gastrin molecule, a series of shortened peptides related to the human little-gastrin-I sequence were synthesized. The biological activities of these gastrin peptides strongly suggest in the pentaglutamic acid sequence a specific information for a pronounced amplification of the hormonal activity.

Amino Acid Sequence↗
PubMed1983

Interaction of GRF with VIP receptors and stimulation of adenylate cyclase in rat and human intestinal epithelial membranes. Comparison with PHI and secretin.

GRF (10(-8) - 10(-5) M) is shown to inhibit competitively the binding of [125I]VIP to human and rat intestinal epithelial membranes. The affinity of GRF for VIP receptor is 700-800-times lower than that of VIP in both species. The order of affinity of different peptides is VIP greater than PHI greater than secretin greater than GRF in rat, and VIP greater than GRF greater than PHI greater than secretin in man. The important species specificity of VIP receptors in recognizing PHI and secretin does not occur in the case of GRF. GRF stimulates adenylate cyclase through its interaction with VIP receptors in rat and human membranes. However, while GRF behaves as a VIP agonist in human tissue, it is a partial agonist/antagonist of VIP in the rat.

Adenylyl Cyclases↗
PubMed1983

Bimodal regulation of pancreatic exocrine function in vitro by somatostatin-28.

The action of natural and synthetic somatostatin-(1--28), [Nle8]somatostatin-(1--28), somatostatin-(15--28), and somatostatin-(1--14) was examined in dispersed acini from guinea pig pancreas. At high concentrations, the 28-amino acid form of somatostatin increased amylase release, outflux of 45Ca, cellular cGMP, and to a lesser extent cellular cAMP. The increase in amylase release was suppressed by dibutyryl cGMP but was not modified by theophylline or atropine. Binding of 125I-labeled [Thr28, Nle31] cholecystokinin-(25--33) was inhibited by [Nle8]somatostatin-(1--28). These effects required the entire 28-amino acid peptide and appeared to result from occupation of cholecystokinin receptors. It is postulated that they involve interactions between the C-terminal and the N-terminal sequences of the molecule with the participation of the amino acid in position 8. At low concentrations, natural and synthetic forms of somatostatin-(1--28) and somatostatin-(15--28) inhibited secretin- and vasoactive intestinal peptide (VIP)-stimulated increases in cellular cAMP concentration. No difference was found between the potency of somatostatin peptides, indicating that the tetradecapeptide somatostatin-(15--28) is sufficient to exert an inhibitory action on secretin- and VIP-stimulated cellular cAMP concentration. By contrast, the somatostatin fragment S-(1--14) was inactive on pancreatic cellular function.

Amylases↗
PubMed1983

Synthesis of the porcine intestinal peptide PHI and its 24-glutamine analogue.

PHI--a new candidate hormone from porcine intestinal tract-- corresponds to a linear heptacosapeptide amide of remarkable sequence homology to the known members of the glucagon family, particularly to the vasoactive intestinal peptide (VIP) and secretin. The position 24 usually occupied by an aminodicarboxylic acid omega-amide, in the present case, however, carries a glutamic acid, thus opening the question of whether this structural feature is related to desamidation in one of the isolation and characterization steps or of whether it is significant for this peptide factor. Consequently the heptacosapeptide amides corresponding to the proposed primary structure and to its 24-glutamine analogue have been synthesized. Comparative chromatographic and biological studies on the natural and the two synthetic products have confirmed the correctness of the primary structure proposed for the isolated PHI. Since [24-glutamic acid] and [24-glutamine]PHI exhibit no significant differences in their biological potencies, the main question is still open of whether the position 24 in native PHI is occupied by the aminodicarboxylic acid omega-amide (glutamine) or by N-substituted derivatives (N-glycosyl).

Amino Acid Sequence↗
PubMed1983

[Syntheses of human little gastrin-I and its leucine-15, norleucine-15 and methoxinine-15 analogs].

Human little gastrin-I is known to exhibit a high tendency to air-oxidation of its methionine-15 residue to the corresponding S-oxide derivative, with concomitant loss of biological activity. Since its leucine-15 analog, even if fully biologically active, differs significantly from the parent hormone in the immunological properties, the norleucine-15 and methoxinine-15 analogues were synthetized. For the required comparative analyses new syntheses of human little gastrin-I and of its leucine-15 analog were additionally elaborated. Upon an optimized condensation of the fragments, followed by the deprotection step, partition chromatography as well as preparative high-performance liquid chromatography led to the desired gastrins in satisfactory yields and high degree of purity as judged by the expected and known side products.

Amino Acid Sequence↗
PubMed1982

Effect of Nin-formylation of the tryptophan residue on gastrin (HG-13) binding and on gastric acid secretion.

The biologically active iodinated [Leu11]human gastrin-13 was found to exhibit high affinity for gastric mucosal cell receptors. We compared its biological activity on rat stomach and its receptor affinity on rat gastric mucosal cells isolated with pronase with those of a reversibly modified derivative obtained by direct Nin-formulation of the Trp10 residue. The results strongly suggested the involvement of the indole-NH group in both the specific binding of gastrin and the triggering of acid secretion.

Animals↗
PubMed1982

Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro.

The rate of degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma was investigated, using high pressure liquid chromatography for the separation and identification of the degradation products. CCK tetrapeptide showed a half-life of 13 min in human plasma while its cleavage in rat plasma occurred at a very high rate (half-life of less than 1 min). The kinetics of disappearance of both sulphated and unsulphated CCK-8 indicated more than a single rate of degradation; the faster degrading system showed a half-life of 18 min for unsulphated CCK-8 and of 50 min for the sulphated peptide in human plasma as compared respectively with 5 and 17 min in rat plasma. The cleavage of CCK-8 was inhibited by bestatin and puromycin, suggesting that aminopeptidases play a major role in the breakdown of this peptide. CCK-9 analogs were rapidly converted into their corresponding octapeptides (half-life of 2.7 min in human plasma). This conversion was inhibited by puromycin and bestatin, suggesting the participation of aminopeptidase(s) probably specific for basic amino acids. CCK decapeptide exhibited a greater stability than the nonapeptides (half-life of 30 and 45 min in human and rat plasma respectively) and also gave rise to CCK-8 as degradation product. This cleavage was not affected by aminopeptidase inhibitors but was decreased by aprotinin (Trasylol), suggesting that trypsin-like and/or kallikrein-like enzyme(s) were involved in the plasma metabolism of this peptide.

Adult↗
PubMed1982

Synthesis of [8-norleucine]somatostatin-28.

Because of the high tendency of natural and synthetic somatostatin-28 to S-oxide formation at methionine-8 via air-oxidation, the 8-norleucine analogue was prepared following the synthetic route previously elaborated for the parent methionine peptide. [Nle8]-somatostatin-28 was obtained at a high degree of purity as judged by different analytical assays. It was found to possess the identical stimulatory effect on amylase release from pancreatic acini as the natural peptide extracted from porcine intestine.

Amino Acids↗
PubMed1982

1-(tert-butylthio)-1,2-hydrazinedicarboxylic acid derivatives. New reagents for the introduction of the S-tert-butylthio group into cysteine and cysteine derivatives.

The sterically hindered tert-butyl thiol reacts smoothly with azodicarboxylic acid derivatives only upon addition of catalytic amounts of sodium alcoholate, yielding crystalline and analytically well characterized 1-(tert-butylthio)-1,2-hydrazinedicarboxylic acid derivatives. These sulfur-activated reagents were found to be stable on storage and well suited as tert-butylthio carriers for the introduction of this thiol-protecting group on cysteine, cysteine derivatives and cysteine peptides; the related compounds are obtained in high yields.

Cysteine↗
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

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↗