title: Bioinspired self-assembled peptide nanofibers with thermostable multivalent α-helices.
abstract: 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.
authors.affiliation: Translational Research Center for Protein Function Control and Department of Materials Science and Engineering, Yonsei University, Seoul 120-749, Korea.
authors.forename: So-hee
authors.initials: SH
authors.lastname: Han
authors.forename: Mun-kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Yong-beom
authors.initials: YB
authors.lastname: Lim
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D015497:HIV-1 / Q000737:chemistry; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013229:Stearic Acids / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D013229:Stearic Acids; D013501:Surface-Active Agents; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; C031183:stearic acid