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Biomedical subjects

T Wieland

Publications and source records attributed to T Wieland.

At least 109 records · Page 6Linked to original sources
PubMed1980

Carbon-13-N.M.R.-spectra of antamanide, several analogues and their alkali ion complexes.

Natural abundance carbon-13 Fourier transform n.m.r.-spectra were obtained of the cyclic decapeptides [Phe4Val6] antamanide (I); antamanide (II); [Tyr5] antamanide (III); [Ala1] antamanide (IV) and their ion complexes (I)-Na+, (II)-Na+, (II)-Li+, (III)-Na+ and (IV)-Na+. Based upon literature data, systematic comparisons and model compounds, a line assignment approach was performed for the majority of the aliphatic carbons. The spectra of the [Ala9Val6] analogues (V) (Bystrov et al., 1972) and II (measured in CD3CN Patel, 1973a, b) and their complexes were also assigned. Characteristic chemical shift variations observed upon complex formation were calculated (delta delta free peptide[Me+ complex) for a number of corresponding carbons, revealing shift changes up to 2.4 p.p.m. Preliminary calculations of the theta angle at selected prolines for some ion complexes are included.

Amino Acid Sequence↗
PubMed1980

Silybin inhibition of amatoxin uptake in the perfused rat liver.

Silybin dihemisuccinate, in a concentration of 0.4 mg/ml, almost completely inhibited the uptake of an amatoxin by the perfused rat liver. Similary, silybin should also interrupt absorption of toxins due to enterohepatic circulation, e.g. in dog and man. This effect may become important in the therapy of human Amanita poisoning.

Amanitins↗
PubMed1979

Reduced phallotoxin uptake by livers of young compared with adult rats.

Using [3H]-demethylphalloin as a tracer the uptake of phallotoxins by the liver of young (6, 12, 16 days old) and adult rats was determined in relation to the dose of toxin administered. The maximum amount taken up by the livers of the young rats was only about 50% of that in adults. Nevertheless, with a dose as high as 55 mg/kg body weight the toxin concentration in the young liver reached more than 30 micrograms/g, being markedly higher than the minimum concentration (approximately 20 micrograms/g) required to cause irreversible damage of the liver in adult rats and death of the animals. This suggests that the tolerance of young rats to phallotoxins cannot solely be explained by the reduced uptake of the toxin.

Aging↗
PubMed1979

Conformation of uncomplexed natural antamanide crystallized from CH(3)CN/H(2)O.

Natural antamanide, a cyclic decapeptide from Amanita phalloides, has been shown to have the same conformation for the backbone and comparable side groups as the biologically active synthetic [Phe(4), Val(6)]antamanide. Packing in the crystal is quite different for the two compounds. Large channels with a polar lining are formed in the crystals of [Phe(4), Val(6)]antamanide, whereas in natural antamanide large channels in the crystal are completely surrounded by the lipophilic side groups of the Pro, Phe, and Ala residues. Antamanide, C(64)H(78)N(10)O(10).8H(2)O.X, crystallizes in space group P2(1)2(1)2(1) with a = 15.88 A, b = 34.88 A, and c = 13.61 A.

Journal Article↗
PubMed1979

Fluorescent phallotoxin, a tool for the visualization of cellular actin.

A fluorescent derivative of phalloidin has been synthesized possessing high affinity to filamentous actin. This compound was used for visualization of actin-containing structures in eukaryotic nonmuscle cells. Due to its low molecular weight (1250), fixation for formaldehyde was sufficient to render the membrane permeable for the labeled peptide. Bundles of microfilaments are the predominant pattern in the flat rat kangaroo PtK1 cells, whereas a net of concentric fibers characterizes the more spherical bovine kidney MDBK cells. Specificity of staining was confirmed by competition experiments with unlabeled phalloidin.

Actins↗
PubMed1978

Influence of phallotoxins and metal ions on the rate of proteolysis of actin.

The rate of proteolytic degradation of rabbit skeletal muscle actin by trypsin, alpha-chymotrypsin, and, mainly, subtilisin was followed by dual wavelength spectroscopy at 285 nm by reference at 320 nm. Phalloidin and phallacidin, two toxic bicyclic heptapeptides from the mushroom Amanita phalloides, protect F-actin against degradation by the proteolytic enzymes. G-actin, which does not combine with phalloidin when maintained in the monomeric state by working at low ionic strength, and bovine serum albumin, which also has no affinity to the toxin, are hydrolyzed at the same rates in the presence or absence of phalloidin. The proteolysis of F-actin is distinctly retarded by KCl alone, i.e., without phalloidin, whereas Mg2+ or Ca2+ as sole cations permit a rather high rate of hydrolysis. An even faster degradation of F-actin by subtilisin is observed in the presence of Mg2+ plus cytochalasin B. Adenosine diphosphate and triphosphate have no influence on the rate of the enzymatic degradation. The S sulfoxide of phalloidin, the nontoxic diastereomer of the toxic R form, exerts only a limited inhibitory effect on the enzymatic hydrolysis; secophalloidin, another nontoxic derivative, which does not bind to F-actin has practically no effect.

Actins↗
PubMed1978

Syntheses of monocyclic and bicyclic peptides of tryptathionine and glycine.

L-3a-Hydroxy-1.2.3.3a.8.8a-hexahydropyrrolo [2,3-b-]-indole-2-carboxylic acid (Hpi), obtained from L-tryptophan by oxidation with peroxyacetic acid (Savige, 1975), after introduction of the Boc-residue at N-1, is coupled with various glycine peptides of S-trityl-L-cysteine to give the Hpi-peptides 6(a-f). By treatment with absolute trifluoroacetic acid these peptides are converted by an intramolecular thiolysis to the monocyclic thioethers 7(a-f). Two of them, 7e and 7f, can be subjected to a second cyclization by the mixed anhydride method thus yielding the bicyclic tryptathionine heptapeptide 8e and octapeptide 8f. In their structures the bicyclic molecules resemble the mushroom phallotoxins and amatoxins, respectively. They show CD spectra closely related to the naturally occurring bicyclic peptides thus indicating conformational similarities. The CD spectra of the other cyclic peptides synthesized are also presented and discussed.

Chemical Phenomena↗
PubMed1978

Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms.

This review gives a comprehensive account of the molecular toxicology of the bicyclic peptides obtained from the poisonous mushrooms of the genus Amanita. The discussion of the biochemical events will be preceded by a consideration of the chemistry of the toxic peptides. The structural features essential for biological activities of both the amatoxins and the phallotoxins will be discussed, also including the most important analytical data. Similar consideration will be given to antamanide, a cyclic peptide, which counteracts phalloidin. In addition, the phallolysins, three cytolytic proteins from Amanita phalloides will be discussed. The report on the biological activity of the amatoxins will deal with the sensitivity of the different RNA-polymerases towards the toxins and with their action on various cell types. Consideration will also be given to systems in which alpha-amanitin was used and can be used as a molecular tool; in the past, many investigators used the inhibitor in molecular biology, genetics, and even in physiological research. As for the phallotoxins, discussion of the affinity of these toxins for actin is provied. Further discussion attempts to understand the course of intoxication by filling in the gap between the first molecular event, formation of microfilaments, and the various lesions in hepatocytes during the intoxication.

Agaricales↗
PubMed1977

Modification of actins by phallotoxins.

Phallotoxins bind to filamentous actin (F-actin) from liver or rabbit muscle with Kdiss approximately 10(-8) M. By this combination the structure of F-actin is stabilized to such an extent that it will be resistant to the depolymerizing action of 0.6 M KI and of deoxyribonuclease I, to denaturation by heat (70 degrees C), and to local ruptures caused by ultrasonication or by cytochalasin B. The structural features of phallotoxins essential for affinity to F-actin are specific.

Actins↗