Peptide Lipid Interaction/ Peptide Transport (M. Dathe, J. Oehlke)
Projects
- LSM-picture of cell-internalized fluorescent peptides
Structural requirements for the cargo delivery ability of peptides
Our strategy has been to undertake a comparative investigation of cellular uptake and biological activity of a model cargo (PNA) conjugated with cell-penetrating peptides and derivatives thereof showing systematicly altered structural properties. The cellular uptake was studied by means of confocal laser scanning microscopy and by use of capillary electrophoresis combined with laser-induced fluorescence detection (CE-LIF) and FACS analysis. The biological activity was studied by means of the "Kole splice-correction-assay." Surprisingly, no significant effects of the structural changes of the peptide-tags could be found irrespective of the cell type used. These findings suggest very limited possibilities in cell selective targeting by altering the structural properties of the delivery peptides. More pronounced structural effects became apparent after energy depletion suggesting the presence of active export pumps and, thereby, offering a promising target for approaching cell selective delivery.
- Multifunctional Micelles and Liposomes
Peptide-modified liposomal and micellar carriers
The highly cationic tandem dimer A2, which is derived from the low-density-lipoprotein-receptor (LDLr)-binding domain of apolipoprotein E (apoE), was used as a vector to induce drug carrier transport across the blood-brain barrier (BBB). In addition to covalent coupling of A2 to liposomes, the physicochemical properties favoured the dipalmitoylated derivative, P2A2, as a highly promising candidate for the development of liposomal as well as micellar nanocarriers stable at pharmacologically relevant time scales. The cell matrix component, heparan sulfate proteoglycan, plays a decisive role in the efficient uptake of the liposomal carrier into BBB-forming capillary endothelial cells. An LDL-receptor-mediated targeting effect could not be detected. Different uptake patterns of the two particulate systems in studies with inhibitors of specific endocytotic pathways pointed to distinct differences in the transport routes, a subject of present investigation.
- NMR-structure of an antimicrobial hexapeptide
Small antimicrobial peptides
Studies of the structural and functional principles of small antimicrobial peptides suggested that the activity-determining structural motif of R- and W-rich hexapeptides is amphipathicity. This biophysical characteristic is based on cyclisation-induced clustering of aromatic side chains and the positioning of the charged residues in the plane of the back bone ring. The peptides act by permeabilising the bacterial membrane. However, their high selectivity for gram negative bacteria seems to be related to interactions with specific components of the outer wall of bacteria. The constrained, amphipathic, and enzymatically resistant hexapeptides will serve in present application-oriented studies as lead compounds for the development of additives in sperm conservation and in vitro fertilisation.
Current Projects:
- Brain targeting using surface-modified nanosuspensions and apolipoprotein E-peptide-covered lipid-based carriers.
DFG Research Group FG: 463 "Innovative Drugs and Carrier System" Project 7 (DA 324/5-2;5-3)
- Design and synthesis of small antimicrobial peptides.
POR INNO II Application-oriented cooperation project between the FMP; IZW, IFN and Biosyntan "Development of antimicrobial peptides for substituting conventional antibiotics and application in reproduction biology" Project 2 (KF0376001MD6)
- Biomaterials: Investigation of the antimicrobial activity of peptide-covered surfaces.
ProFIT Project (10134769)
