Bioinspired Self-Assembled Peptide Nanofibers with Thermostable Multivalent α-Helices

The stabilization of peptide's active conformation is a critical determinant of its target binding efficiency. Here we present a structure-based self-assembly strategy for the design of nanostructures with multiple and thermostable alpha-helices using bioinspired peptide amphiphiles. The design principle was inspired by the oligomerization of the human immunodeficiency virus type-1 (HIV-1) Rev protein. Our goal was to find a strategy to modify the Rev protein into a chemically manageable self-assembling peptide while stabilizing its alpha-helical structure. Instead of using cyclic peptides for structure stabilization, this strategy utilizes the pseudocyclization for helix stabilization. The self-assembly induced stabilization of alpha-helical conformation could be observed, and the alpha-helices were found to be stable even at high temperature (at least up to 74 degrees C). Conjugation of a hydrophobic alkyl chain to the Rev peptide was crucial for forming the self-assembled nanostructures, and no nanostructures could be obtained without this modification. Because chemical modifications to the alpha-helical peptide domain can be avoided, potentially any alpha-helical peptide fragment can be grafted into this self-assembling peptide scaffold.