Synthesis of Model Systems for SNARE Mediated Membrane Fusion Based on PNA/PNA Base Pair Recognition

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SNARE proteins are regarded as key players in membrane fusion. In neuronal exocytosis, for example, they cause synaptic vesicles to fuse with the presynaptic membrane in order to release neurotransmitters. The detailed mechanism of this process is still a matter of debate. SNARE model systems are valuable tools to study membrane fusion because they mimic the action of SNARE proteins in vitro. In this thesis, SNARE model systems have been developed which aim at mimicking the assumed SNARE zippering that initiates SNARE-mediated membrane fusion. The model peptides exhibit novel artificial peptide nucleic acid hybrid recognition units attached to transmembrane anchors. The thesis describes how the model peptides are designed and synthesized and how the fusogenicity of the peptides is analyzed. Combining bulk lipid mixing assays with the techniques of fluorescence cross-correlation spectroscopy and dynamic light scattering allowed obtaining a detailed picture on the fusogenic behavior of the investigated model systems.