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Biomedical subjects

M Bodanszky

Publications and source records attributed to M Bodanszky.

At least 55 records · Page 3Linked to original sources
PubMed1978

Pancreatic secretory activity of secretin5-27 and substituted analogues.

The effect of secretin5-27 and four substituted analogues (9 Gln-secretin5-27, 15-Asn-secretin5-27, 9-Gln-15-Asn-secretin5-27, and 15-Lys-secretin5-27) on pancreatic secretion in the rat and guinea pig was examined. Secretin5-27 retained significant pancreatic secretory activity in both species. Its efficacy (intrinsic activity) relative to secretin was much higher in the rat (0.2) than in the guinea pig (0.03). The activity of secretin5-27 was not affected by a single or dual substitution of carboxylic acid residues by the corresponding carboxamides or by lysine despite a substantial decrease in the helical character of the peptide.

Animals↗
PubMed1978

Side reactions in peptide synthesis. VI. A reexamination of the benzyl group in the protection of the side chains of tyrosine and aspartic acid.

The acid catalyzed O leads to C migration of the benzyl group in the side chain of tyrosine could be reduced by applying HBr in a mixture of phenol and p-cresol instead of BHr in trifluoroacetic acid for acidolytic deprotection. This side reaction occurs also during the removal of Boc groups. The loss of O-benzyl protection and the formation of 3-benzyltyrosine residues could be suppressed by the application of a 7:3 mixture of trifluoroacetic acid and acetic acid. The acid- and base-catalyzed ring closure of beta-benzylaspartyl residues to aminosuccinyl derivatives was also studied. In this case HBr in trifluoroacetic acid was found to be relatively harmless. Deprotection with HBr in a mixture of trifluoroacetic acid and p-cresol can be applied for peptides that contain both beta-benzylaspartyl and O-benzyltyrosyl residues. An attempt to reduce the rate of the base-catalyzed side reaction by application of hindered tertiary amines was abandoned because the tertiary amines which were effective in this respect let to significant reduction of the rate of the desired reaction, the aminolysis of active esters, as well. A satisfactory solution for the problem was found in the selective catalysis of the active ester reaction with 1-hydroxybenzotriazole or 4-dimethyl-aminopyridine. These catalysts do not enhance the rate of ring closure and in their presence essentially pure beta-benzylaspartyl peptides can be produced in good yield.

Aspartic Acid↗
PubMed1978

Side reactions in peptide synthesis. VII. Sequence dependence in the formation of aminosuccinyl derivatives from beta-benzyl-aspartyl peptides.

The base catalyzed ring closure in t-Boc-Asp-X beta-napthylamides was examined in a series of 2-peptide derivatives in which position X was occupied by the neutral and acidic amino acid residues that occur in proteins. Bulkiness and functional groups in the side chain of X have a major effect on the rate of cyclization, e.g. acidic groups slow down the formation of aminosuccinyl derivatives. Rate-enhancing effect can be observed in serine and threonine, while the side reaction is unexpectedly slow when X is methionine.

Amino Acids↗
PubMed1978

Side reactions in peptide synthesis. IX. Suppression of the formation of aminosuccinyl peptides with additives.

The base-catalyzed ring closure of beta-benzylaspartyl peptides was efficiently suppressed by the addition of phenols (with electron-withdrawing substituents) to the reaction mixtures. From a series of compounds tested, 2,4-dinitrophenol and pentachlorophenol were the most effective. No direct relationship was found between the acidity of the additives and their ability to suppress the formation of aminosuccinyl peptides. The applicability of 2,4-dinitrophenol and pentachlorophenol in practical syntheses was also examined.

Acylation↗
PubMed1977

Cholecystokinin (pancreozymin). 3. Synthesis and properties of an analogue of the C-terminal heptapeptide with serine sulfate replacing tyrosine sulfate.

The influence of tyrosine O-sulfate, the 27th residue in the sequence of cholecystokinin (pancreozymin) (CCK-PZ) on calcium outflux in isolated pancreatic cells of guinea pigs, was studied by replacing this residue in the biologically active C-terminal heptapeptide, CCK-PZ-(27--33) (I), with L-serine O-sulfate. The synthetic analogue Ser(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2 (IV), produced the half-maximal outflux observed with I, if applied at about 250 times higher concentration. The unsulfated form of IV was about ten times less potent than unsulfated I. Thus, in the effect on the calcium outflux, serince cannot replace tyrosine without a major loss in potency; a sulfate ester group in position 27 is important but in itself not sufficient for full potency. Interestingly, if the terminal amino group of the heptapeptide is left protected by a tert-butyloxycarbonyl group, the potencies of the derivatives of both I and IV were slightly, but significantly, higher than those of the free peptides.

Animals↗
PubMed1977

Synthesis and pharmacological properties of the N-terminal decapeptide of the vasoactive intestinal peptide (VIP).

The decapeptide derivative, L-histidyl-L-seryl-L-aspartyl-L-alanyl-L-valyl-L-phenylalanyl-L-threonyl-L-aspartyl-L-asparaginyl-L-tyrosine methyl ester, corresponding to the N-terminal sequence of both porcine and chicken VIP was synthesized in solution, by the stepwise strategy. Its pharmacological properties resemble those of VIP itself, but with a much lower potency, comparable to that of peptides with C-terminal sequences. The presence of two independent sequences carrying similar instructions was recognized in VIP.

Amino Acid Sequence↗
PubMed1977

Active esters in the formation of ester bonds between amino acids and polymeric supports.

The imidazole catalyzed transesterification of active esters was used for the formation of the ester bond between the carboxyl group of protected amino acids and the hydroxyl group of a polymeric support applied in solid phase peptide synthesis. Anchoring of the C-terminal residue to the hydroxymethyl polymer proceeded smoothyl and provided a high degree of incorporation. No racemization was observed in the imidazole-catalyzed alcholysis. The procedure could be carried out with various active esters such as esters of o-and p-nitrophenol, 2,4,5-trichlorophenol, pentachlorophenol and N-hydroxysuccinimide.

Amino Acid Sequence↗
PubMed1977

Ring formation in a pentapeptide with alternating L and D residues: an analogy to cyclization in the biosynthesis of peptide antibiotics.

Acetylation of L-isoleucyl-D-alanyl-D-alanyl-L-valyl-D-leucine with acetic anhydride followed by methylation with diazomethane yielded the expected acetylpentapeptide methyl ester with molecular weight 541, but also resulted in the formation of a by-product with molecular weight 555. The incorporation of the mass corresponding to CH2 seems to be due to ring closure--via a mixed anhydride--and methylation of the cyclol derivative thus formed. A preferred, ring-like conformation stabilized by intramolecular hydrogen bonds that in turn are the consequences of the alternation of D- and L- residues in the sequence, is invoked as explanation for the unexpected cyclization. This assumption is supported by the conversion of the pentapeptide methyl ester to desthiomalformain in molten imidazole.

Acetylation↗
PubMed1977

Side reactions in peptide synthesis. V.A reexamination of the mixed anhydride method.

Acylation of amino acid beta-naphthylamides with protected (Boc) amino acidisobutylcarbonic acid mixed anhydrides resulted in each case in the formation of some undesired by-product: an isobutyloxycarbonylamino acid beta-naphthylamide. The amount of this second acylation product was particularly high, with the hindered amino acids valine and isoleucine as carboxyl-components. The nature of the amino component had no major influence on the extent of this side reaction.

Acylation↗
PubMed1977

The role of some polar amino acid residues in secretin.

Three analogues of S5-27, the tricosapeptide with the carboxyl-terminal sequence of secretin, were studied. In the analogues, the acidic residues at positions 9 and 15 of S5-27 were replaced by the neutral residues glutamine and asparagine. These changes resulted in a decrease in immunoreactivity. Binding to an antibody against secretin could be correlated with the changes in the conformation of the synthetic analogues.

Amino Acid Sequence↗
PubMed1976

A re-examination of the conformation of secretin in water.

An examination of a series of peptides corresponding to partial sequences of secretin and the application of empirical conformational parameters to the sequence has reopened the question about the position of the short helical stretch in the folded chain. In earlier studies, this was tentatively placed near the N-terminus, while newly accumulated evidence points to the C-terminal area. The possible role of ion pairs in the stabilization of the folding was investigated by the preparation and examination of synthetic analogues of the C-terminal tricosapeptide part of secretin. The carboxyl groups of glutamic acid (in position 9) and of aspartic acid (in position 15) were replaced by carboxamides. The 9-glutamine and the 15-asparagine analogues show a significant decrease in helical character. This loss of "structure" is even more pronounced in the 9-glutamine-15-asparagine tricosapeptide. Thus, ion-pair formation is indeed implicated as one of the forces which stabilize the folded conformation of the chain. Possible correlations between biological activity and secretin-like architecture were studied on several smooth muscle preparations.

Amino Acid Sequence↗
PubMed1976

High resolution mass spectra of malformin and related cyclic peptides.

A comparison of the high resolution mass spectra of synthetic and natural preparations of malformin provided new evidence for the revised structure: (see article): The interpretation of the mass spectra was aided by the examination of the spectra of the synthetic peptides, desthiomalformin and enantio-5-valine malformin.

Disulfides↗
PubMed1976

Interaction of peptides related to secretin with hormone receptors on pancreatic acinar cells.

Three analogues of the carboxyl-terminal tricosapeptide of secretin (S5-27), one with glutamine replacing glutamic acid in position 9 (9-Gln-S5-27), a second with asparagine substituted for aspartic acid in position 15 (15-Asn-S5-27), and a third with both replacements (9-Gln-15-Asn-S5-27) were tested for their ability to interact with hormone receptors on dispersed pancreatic acinar cells. Each of these analogues inhibited binding of 125I-labeled vasoactive intestinal peptide (VIP). None of the analogues increased cellular cyclic AMP but each inhibited the increase in cellular cyclic AMP produced by secretin or VIP. At the high affinity VIP receptor (the low affinity secretin receptor) each analogue had an apparent affinity which was greater than that for S5-27, whereas at he low affinity VIP receptor (the high affinity secretin receptor), each of the analogues had an apparent affinity which was the same as that for S5-27. Thus, in S5-27, substituting glutamine in position 9 or asparagine in position 15 makes the fragment more VIP-like but not less secretin-like. These results also provide additional evidence that the receptor having a low affinity for secretin and a high affinity for VIP is functionally distinct from the receptor having a high affinity for secretin and a low affinity for VIP.

Amino Acid Sequence↗