Diskriminantenalgebren quadratischer Formen

Ohne ZusammenfassungDiese Note enthält die wesentlichen Ergebnisse meiner Diplomarbeit [3]. Herrn Professor Martin Kneser danke ich für viele Anregungen und für Hilfe bei der Abfassung dieser Note.     

Production of the Bengamide Class of Marine Natural Products in Myxobacteria: Biosynthesis and Structure–Activity Relationships

The bengamides, sponge‐derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), have been intensively investigated as anticancer compounds. We embarked on a multidisciplinary project to supply bengamides by fermentation of the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize their properties as drug leads. The characterization of the biosynthetic pathway revealed that bacterial resistance to bengamides is conferred by Leu 154 of the myxobacterial MetAP protein, and enabled transfer of the entire gene cluster into the more suitable production host M. xanthus DK1622. A combination of semisynthesis of microbially derived bengamides and total synthesis resulted in an optimized derivative that combined high cellular potency in the nanomolar range with high metabolic stability, which translated to an improved half‐life in mice and antitumor efficacy in a melanoma mouse model.     

Generation of potential energy surfaces in high dimensions and their haptic exploration

A method is proposed for the automated generation of potential energy surfaces in high dimensions. It combines the existing algorithm for the definition of new energy data points, based on the interpolating moving least-squares algorithm with a simulated annealing procedure. This method is then studied in a haptic quantum chemistry environment that requires a fast evaluation of gradients on a potential energy surface with automatic improvement of its accuracy. As an example we investigate the nitrogen binding pathway in the Schrock dinitrogen fixation complex with this set-up.     

Determination of carbonyl compounds in the low ppb-range by capillary electrophoresis

Summary A new method for analysing carbonyls (aldehydes and ketones) by capillary electrophoresis (CE) is described. The carbonyls are derivatized with DNSH [5-(dimethylamino)naphthalene-1-sulphonehydrazide, Dansylhydrazine] to form detectable compounds and also to form negative charged molecules (buffer pH 7.1). Detection is carried out by UV or, alternatively, by fluorescence. Eight carbonyls are separated in less than 8 min. Electrokinetic injection is made by using a new experimental set-up. The electroendosmatic flow (EOF) is reversed during sample injection by pressure. Results are compared with HPLC-analysis as the most common method in carbonyl analysis.Dedicated to Professor Dr. Wilhelm Fresenius on the occasion of his 80th birthday