Mechanistic Studies on Diamine Oxidase

To investigate the enzyme pea seedling diamine oxidase our studies concentrated on three main areas: 1. mechanistic studies of the oxidative deamination of primary diamines catalysed by diamine oxidase; 2. oxidation of aromatic compounds with amine side chains by pea seedling diamine oxidase; and 3. inhibition of pea seedling diamine oxidase. To make use of diamines synthesised within the research group a fourth area was studied: 4. synthesis of cisplatin analogues. Mechanistic Studies of the Diamine Oxidase-Catalysed Deamination of Diamines Diamine oxidase catalyses the oxidative deamination of diamines to their corresponding aminoaldehydes (Scheme A). To test the hypothesis that the diamine oxidase-catalysed oxidation proceeds via an enamine intermediate (i) we prepared a number of alpha,o-diamines labelled with deuterium at the beta-positions. The [2H4]-labelled diamines and the corresponding unlabelled diamines were incubated with pea seedling diamine oxidase and the products were trapped with benzoylacetic acid in situ. (Scheme B). This gave substituted acetophenone products (ii) which were analysed by NMR and mass spectrometry. From a comparison of the spectroscopic data we were able to show that the enamine intermediate (i) is not involved in the enzymatic process. 2. Oxidation of Aromatic Compounds with Amine Side Chains by Pea Seedling Diamine Oxidase A range of quinoline, pyridine, thiophene and pyrrole derivatives with amine side chains were synthesised and tested as substrates of pea seedling diamine oxidase using a spectrophotometric assay which measures the hydrogen peroxide by-product of the enzymatic reaction. From this assay Vmax and Km values were obtained for the oxidation of each substrate using diamine oxidase. The Vmax is the maximal rate of oxidation and gives an indication of the oxidation rate for the various substrates. The KM is a measure of the strength of the enzyme-substrate complex and determines the binding efficiency of the substrate to the enzyme. Analysis of this kinetic data provided information on the enzymatic process and the nature of the pea enzyme's active site. Comparison of the kinetic data obtained from the various aromatic substrates enabled us to study the effect on the binding affinity and rate of oxidation from changes to the ring size of the substrates. The role of the second amine group was also explored using nitrogen heterocycles with amine side chains. 3. Inhibition of Pea Seedling Diamine Oxidase Polyamines are known to be essential in the growth and replication of cells, and diamine oxidase plays a key role in the polyamine metabolism with the oxidative deamination of diamines. Inhibitors of diamine oxidase should therefore have a considerable effect on the polyamine metabolism and hence cell growth. With this in mind inhibitors of diamine oxidase may possess important biological activity. Compounds which were shown to be poor substrates but efficient binders of the pea seedling diamine oxidase from our initial studies were tested as inhibitors. These tests were carried out using the same spectrophotometric assay as before, but which had been modified to include the inhibitor. Most of the compounds tested were found to inhibit the diamine oxidase-catalysed deamination of putrescine and were shown to be competitive inhibitors. 4. The Synthesis of Cisplatin Analogues Cisplatin (iii) is a widely used anticancer drug, but its therapeutic value is limited by the number of toxic side effects which it exhibits. To make use of the diamines available from other studies, we attempted to make cisplatin analogues with various diamines used as bidentate ligands. As there were no examples of unsaturated diamines being used in cisplatin analogues we used cis-1.4-diaminobut-2-ene (iv) which had previously shown antibiotic activity. We made our target compound cis-1,4-diamino(dichloro)-platinum (II) (v), but were unable to make our second target cis-1,4-diaminobut-2-ene(1,1-cyclobutanedicarboxylato)platinum (II) (vi)

Reise nach Istanbul.

Donated by Klaus KreiserReprinted from in : Süddeutschen Zeitung Nr. 293., 10.11.1955

5 Chorlieder: (op. 16)

5 engagierte, hochexpressive Lieder für 4- bis 6stimmigen gemischten Chor, zwei Lieder davon mit obligatem Klavier. Charakter und auch Art des Satzes sind durchaus unterschiedlich. Die Spanne reicht von einfacher Linie im Chor mit virtuosem Klavierpart als Kontrapunkt über einen aphoristisch kurzen Chorsatz und einem reinen Klangstück ohne Text bis zu einem bedrohlich sich steigernden Fugato. Es handelt sich dabei nicht um einen festen Zyklus, d.h. die Lieder können auch einzeln gesungen werden, wiewohl eine Gesamtaufführung in der angegebenen Reihenfolge natürlich erwünscht ist. Die Texte stammen von Wolfgang Borchert und Marie-Luise Kaschnitz.:1. Versuch es - S/A/T/B/Piano 2. Obertöne - S/A/T/B 3. Intermezzo - S/MS/A/T/Bar/B 4. Weißnoch - S/MS/A/T/Bar/B 5. Du sollst nicht - S/MS/A/T/Bar/B/Pian

Description of a village by Marie Luise Kaschnitz : translation and introduction

Germanic Studie

[Lieber Dr. Grubel].

Handwritten and signed letter from Marie Luise Kaschnitz to Fred Grubel of the Leo Baeck Institute regarding her poem "Am Strande," which was included in the 1968 German Advanced Placement examination. Included with the letter is a copy of the part of the examination containing the poem and a letter from Grubel to Kaschnitz about the examination.Marie Luise Kaschnitz was born Marie Luise von Holzing-Berslett in Karlsruhe in 1901. She grew up in Potsdam in Berlin and worked in the book trade in Weimar and Munich. In 1925, she married Austrian archeologist Guide Freiherr von Kaschnitz-Weingerg. The couple lived in Rome (1926-32, 1953-56), Königsberg (1932-37), Marburg (1937-41) and Frankfurt am Main (1941-53). After her husband's death in 1958, Marie Luise Kaschnitz lived in Frankfurt as a writer and novelist. She died in Rome in 1974.The original German-language inventory is available in the folderProcessed for digitizatio