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Abstract

Membrane fusion is an essential process in nature, accomplished by the specific interaction of SNARE proteins. SNARE model systems, in which SNARE domains are replaced by small artificial units, represent valuable tools to study membrane fusion in vitro. The synthesis and analysis of SNARE model peptides is presented that exhibit a recognition motif composed of two different types of peptide nucleic acid (PNA) sequences. This novel recognition unit is designed to mimic the SNARE zippering mechanism that initiates SNARE protein mediated fusion. It contains N‐(2‐aminoethyl)glycine‐PNA (aeg‐PNA) and alanyl‐PNA, both recognizing the respective complementary strand differing in duplex topology and double strand forming kinetics. The duplex formation of PNA hybrid oligomers as well as the fusogenicity of the model peptides in lipid mixing assays are characterized and found to induce liposome fusion. As an unexpected discovery, peptides with a recognition unit containing only five aeg‐PNA nucleo amino acids were sufficient and most efficient to induce liposome fusion.