Bioinspired Self-Assembled Peptide Nanofibers

Bioinspired Self-Assembled Peptide Nanofibers with Thermostable Multivalent α-Helices
S.-h. Han, M.-k. Lee,  Y.-b. Lim, Biomacromolecules, Article ASAP
DOI: 10.1021/bm400233x
Publication Date (Web): April 3, 2013
Copyright © 2013 American Chemical Society

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 α-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 α-helical structure. Instead of using cyclic peptides for structure stabilization, this strategy utilizes the pseudocyclization for helix stabilization. The self-assembly induced stabilization of α-helical conformation could be observed, and the α-helices were found to be stable even at high temperature (at least up to 74 °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 α-helical peptide domain can be avoided, potentially any α-helical peptide fragment can be grafted into this self-assembling peptide scaffold.