Marion Zerlin

Specific binding of low molecular weight ligands with direct optical detection

The characterization of low molecular weight ligand interaction with receptor molecules is of importance for the investigation of biological processes and for drug research. We report on the investigation of the binding of low molecular weight ligands to immobilized receptors by label-free detection. Reflectometric interference spectroscopy, an optical transducer which allows the monitoring of a few picograms per square millimetre changes in surface coverage, was used to study two model systems. In both cases detection of the binding event was successful. High affinity binding of biotin to immobilized streptavidin was clearly detectable at receptor surface concentrations as low as 1-2 x 10(10) binding sites/mm2. Linear correlation between the receptor surface concentration and the response to biotin binding was observed. Using immobilized DNA, we investigated the binding of common intercalators with respect to kinetics and thermodynamics by evaluation of the association and the dissociation part of the binding curve. Bi-exponential increase and decrease of intercalator loading was observed, indicating complex interaction kinetics. The four structurally different intercalators showed significant distinction in binding kinetics and equilibrium signals. Improvement of experimental parameters is required to obtain more reliable kinetic data.

First Glycosylation of Decarestrictine B and D: A Route to Hybrid Antibiotics

A set of new hybrid antibiotics can be generated by coupling the naturally occurring ten-membered lactones decarestrictine B and D, which lower cholesterol levels, with deoxygenated glycosyl donors. As demonstrated for bisglycoside 1 these novel glycoconjugates can show DNA-binding properties.

Manipulation of Microbial Metabolite Pattern. 1. Initiation of Obscurolide Biosynthesis in a Streptozoline-producing Streptomycetes Strain

Abstract Manipulation of the secondary metabolite pattern was studied by feeding various compounds into growing cultures of the streptazolin (1)-producing organism Streptomyces sp. (strain FH-S 2184). Besides an increase of the yield of (1),caused by a number of primary metabolites exclusively, the feeding of ammonium ions initiated the biosynthesis of the obscurolides A2 (2) and A3 (3).

Manipulation of Microbial Metabolite Pattern, 2. Initiation of Streptovaricine and Tryptophan-Dehydrobutyrin-Diketopiperazine Biosynthesis in a Marginolactone-Producing Actinomycetes Strain

Abstract Manipulation of the secondary metabolite pattern was studied by feeding various amino acids into cultures of the ‘talented’ Streptomyces sp. (strain FH-S 1623), which already has been found to produce marginolactones (oasomycins A to F, as well as desertomycins A, B, and D), neoaureothin and red pigments of the prodigiosin-type. Feeding of 10 g/l of L-tryptophan initiated the biosynthesis of metabolites of the streptovaricin-complex [streptovaricin C (7) and G (8)] as well as of tryptophan-related metabolites like tryptophan-dehydrobutyrin-diketopiperazin [(TDD (4)].