Fakultät für Chemie - Former
Uni von A-Z
Bielefeld University > Department of Chemistry > Organic Chemistry III > Team > Former

Personal data for Dr. Patrik Plattner

  Dr. Patrik Plattner
Dr. Patrik Plattner
Scientific co-worker
Room: F2-263
Phone: 0521 106 2145

Topic 1: Synthesis and modification of homoserine lactones

Quorum sensing (QS) is a cell-density dependent phenomenon of bacterial colonies. This system facilitates them to sense the excess of a critical cell concentration. Small amounts of permanently produced signal molecules get enriched and initiate a specific gene expression. In gram-negative bacteria N‑acyl‑homoserine lactones (AHLs) are utilized as signal molecules.

Synthesis and modification of those molecules, especially of AHLs was done to investigate the function of their receptor proteins and the following protein-DNA interaction. For this purpose the modifications should not harm the biological activity but offer the opportunity to introduce reporter groups. Starting with L-methionine as a chiral substrate, cis and trans‑3‑hydroxy‑L‑homoserine lactone was synthesized. After acylation of the amino function with fatty acids full activity was maintained, which could be proven by electrophoretic mobility shift assays (EMSA). Further esterification of the hydroxyl group was done to introduce triethylene glycol based spacer unit. It can be immobilized on a solid matrix or conjugated to reporter groups. The hydrophilic spacer also increases the solubility in aqueous systems. All products have been characterized by standard techniques.

Maintained bioactivity renders this functionalized AHL appropriate as a probe for investigations of QS systems (SPR, AFM, fluorescence studies) and purification of interaction partners by affinity chromatography.

Topic 2: Synthesis and Evaluation of Peptide Analogues as functional Probes targeting Matrix Metalloproteinases

The isolation and detection of low abundant enzymes and proteins is one of the most challenging tasks in bioanalytical and pharmacological fields, especially if information about their state of activity is required. For this purpose tailored solutions for addressing the members of a protein family are required. Peptide chemistry provides established methods to assemble building blocks to construct such molecular probes. We chose matrix metalloproteinases (MMP) for validation of such an approach. This protein family processes and degrades various extracellular matrix proteins and possesses a highly conserved catalytic site with a zinc ion in its centre. Most of the known and potent inhibitors are peptidomimetics containing zinc chelating hydroxamate groups (e. g. marimastat). Although it binds reversibly, it is potent and active against a wide range of metalloproteinases. It was chosen as synthetically available binding group to target the protein in its active state. It was modified by peptide chemistry in order to introduce multiple functions. Depending on the purpose, different reporter groups, photoreactive or cleavage sites were chosen. The probes were tested positively to inhibit various human recombinant MMPs using activity assays. MMP were isolated using Streptavidin coated magnetic beads and a biotinylated probe. Furthermore a photoreactive group was introduced to enhance the binding to the target protein. A covalent interaction was achieved by irradiation of a probe protein mixture, isolation with magnetic beads and cleavage from the beads.