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Biomedical subjects

U Ragnarsson

Publications and source records attributed to U Ragnarsson.

At least 73 records · Page 4Linked to original sources
PubMed1979

Peptide inhibition of mammalian histidine decarboxylase.

The hypothesis that N-terminal histidine peptides might act as inhibitors to histidine decarboxylase was investigated. A murine mastocytoma was utilized as enzyme source. The crude extract of this tissue exhibits high rates of decarboxylation of both histidine and DOPA and was used to establish the specificity in the effect of the compounds tested. For kinetic analyses a highly purified histidine decarboxylase fraction was used. The effect of some representative peptides on both enzyme activities were recorded. Histidine decarboxylase exclusively was inhibited by N-terminal histidine peptides. None of the other peptides investigated interfered negatively with this enzyme. This inhibition was consistent in the purified preparation and appeared to be more pronounced with increasing hydrophobicity in the second amino acid. Histidyl-phenylalanine was found to be about 100-fold as potent as the commonly used specific histidine decarboxylase inhibitor alpha-methyl histidine. It is concluded that small peptides with histidine as the N-terminal amino acid might act as specific inhibitors for mammalian histidine decarboxylase. An analog effect of small tyrosyl or phenylalanyl peptides was not seen for the DOPA decarboxylase.

Animals↗
PubMed1978

Solid phase synthesis of apamin, the principal neurotoxin in bee venom. Isolation and characterization of acetamidomethyl apamin.

The synthesis of apamin, the principal neurotoxin in bee venom, has been accomplished by the solid phase method on a benzhydrylamine resin, 2-Phenylisopropyloxycarbonyl amino acids were used throughout the synthesis except for the C-terminal histidine. Improved yields in the coupling steps in the N-terminal part of the molecule were obtained by coupling each amino acid both in dichloromethane and dimethylformamide. The use of acetamidomethyl as an S-protecting group for cysteine made it possible to isolate and purify the linear peptide. The deblocked and oxidized peptide was fractionated by ion-exchange chromatography (Bio-Rex 70) to obtain a highly purified apamin with full biological activity and with the same physical and chemical properties as the natural peptide. Circular dichroism (CD) spectra of the synthetic and natural apamin were identical.

Amino Acid Sequence↗
PubMed1977

Failure of the putative IgE pentapeptide to compete with IgE for receptors on basophils and masts cells.

We have examined the claim that a pentapeptide resembling a portion of epsilon-chain of IgE can inhibit allergic reactions by competing with IgE for basophil-mast cell IgE receptors. Four laboratories with expertise in different areas collaborated. The following was found. (1) There was no evidence, by autoradiography, that the pentapeptide could block IgE fixation to basophils or displace IgE from these cells. (2) There was no evidence, by histamine release studies that the pentapeptide could block basophil sensitization or remove IgE from actively sensitized cells. The pentapeptide, also, did not impair antigen-induced histamine release. (3) There was no evidence that the pentapeptide could block the skin test response in Prausnitz-Küstner testing with the antigen injected intradermally or orally administered. Neither the correct pentapeptide sequence from the epsilon-chain nor the Fc" fragment of IgE impaired the P-K test. In each series of experiments, IgE myeloma protein, as a positive control, blocked the allergic response. The failure of the pentapeptide to block these reactions was observed at molar ratios of pentapeptide/IgE of 10(6) to 10(7). Our results, therefore, provide no evidence for competition between the pentapeptide and IgE. Even if there should be some weak affinity between the pentapeptide and IgE receptors on basophils or mast cells this would, by virtue of quantitative considerations, be of no clinical relevance.

Autoradiography↗
PubMed1976

Synthesis of peptides by fragment condensation on a solid support. II. A scheme for preparation of 4,8-disubstituted vasopressins evaluated on 8-arginine-vasopressin.

A convenient scheme for the synthesis of 4,8-disubstituted vasopressins has been designed and its usefulness evaluated in the preparation of one of the parent hormones, 8-arginine-vasopressin. The main feature of the scheme involves preparation of two protected tripeptide fragments, Z-Cys(Bzl)-Tyr(Bzl)-Phe and Boc-Asn(Mbh)-Cys(Bzl)-Pro which are incorporated in a synthesis on a solid support. Both tripeptides were prepared conventionally with the carboxyl groups protected as benzyl esters. The benzyl-ester groups were removed by transesterification with 2-dimethylaminoethanol and subsequent hydrolysis. To avoid racemization in the coupling step with the fragment containing a C-terminal phenylalanine, N-hydroxysuccinimide was added. After removal of the peptide from the resin, deprotection, oxidation and desalting, final purification was effected by ion-exchange chromatography. Apart from the main product, which exhibited full pressor activity, only small amounts of impurities could be isolated.

Arginine Vasopressin↗
PubMed1975

Syhthesis of peptides by fragment condensation on a solid support. I. Application in preparation of bradykinin.

Two tripeptides and one dipeptide, protected except at the carboxyl ends, have been prepared in solution and used as intermediates in a new synthesis of bradykinin on a solid support. Condensation of the two tripeptides to the resin was effected in satisfactroy yield with dicyclohexylcarbodiimide plus N-hydroxysuccinimide. The partial epimerization that might occur by such an approach was explicitly verified to be without practical importance in this case. The crude product contained only traces of impurities and yielded, after purification, bradykinin of high purity. Both the crude and purified bradykinin exhibited full biological activity.

Amino Acid Sequence↗