Distance Regulated Vesicle Fusion and Docking Mediated by β-Peptide Nucleic Acid SNARE Protein Analogues

Artificial SNARE analogues derived from SNARE proteins, which mediate synaptic membrane fusion, are of interest. They mimic the tetrameric α-helix bundle of the SNARE motif with various bio-oligomer recognition units. Interaction between complementary oligomers linked to the respective membrane by lipid or peptide anchors leads to proximity of vesicles and to fusion of lipid bilayers. β-Peptide nucleic acids were introduced as hybrid oligomers with the native SNARE protein transmembrane/linker sequence, in order to evaluate a fusion system that allows distance tuning of approaching membranes. Formation of a four-base pair β-PNA double strand with 20 Å length is sufficient for vesicle membrane fusion. Elongation of the recognition β-PNA duplex in the linker region yielded a 40 Å β-peptide duplex and provided a vesicle-vesicle distance that only supported hemifusion of vesicle membranes.