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Prof. Dr. Joachim Seelig

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Cell-penetrating petides, protein folding and multi-drug resistance

Research Project  | 2 Project Members

Project A Cell penetrating peptides have become interesting tools for trans-membrane transport studies and are investigated in pharmacological applications to transport protein and nucleic acids across cellular membranes. Different pathways are possible, ranging from detergent-like diffusion to binding to sulfated glycosamines, coupled with endocytosis. The details of membrane passage will be investigated with chemically modified CPPs to gain insight into the mechanistic details. The proposed modifications include pegylation, acylation with long chain fatty acids, and replacing polar amino acid by non-polar ones. The working hypothesis is to shift the hydrophilic amphipathic hydrophobic balance and to correlate it with membrane binding and cellular uptake. In a second project we will investigate (i) the membrane-induced random coil <-> beta-structure equilibrium of Alzheimer peptides and (ii) the pH-induced trans-membrane flip of the LAH4 peptide with isothermal titration calorimetry, dynamic light scattering, analytical ultracentrifugation, and spectroscopic methods. Project B Drug absorption across biological membranes is determined by passive influx and active efflux of drugs by ATP binding cassette (ABC transporters). We have investigated both processes with a special emphasis on active efflux by the ABC transporter P-glycoprotein (ABCB1). We developed a new assay that allows measuring the ATPase activity in cells and provided direct evidence for a substrate transporter interaction based on a modular binding principle.