Synthesis of PNA-Peptide Conjugates as Functional SNARE Protein Mimetics

PNA-peptide conjugates are versatile tools in chemical biology, which are employed in a variety of applications. Here, we present the synthesis of PNA-peptide conjugates that serve as SNARE protein-mimicking biooligomers. They resemble the structure of native SNARE proteins but exhibit a much simpler architecture. Incorporated into liposomes, they induce lipid mixing, so that they can be used to study the SNARE-mediated membrane fusion in a simplified setting in vitro. They consist of artificial SNARE recognition units made out of PNA oligomers, which are attached to the native linker and transmembrane domains of two neuronal SNAREs. The PNA-peptide conjugates are synthesized via solid-phase peptide synthesis in a continuous fashion starting with the peptide part, followed by assembly of the PNA recognition unit. On top, we describe a strategy to synthesize PNA-peptide conjugates in a fully automated fashion by using a peptide synthesizer.