Hexagonally Ordered Arrays of α-Helical Bundles Formed from Peptide-Dendron Hybrids

Abstract

Combining monodisperse building blocks that have distinct folding properties serves as a modular strategy for controlling structural complexity in hierarchically organized materials. We combine an α-helical bundle-forming peptide with self-assembling dendrons to better control the arrangement of functional groups within cylindrical nanostructures. Site-specific grafting of dendrons to amino acid residues on the exterior of the α-helical bundle yields monodisperse macromolecules with programmable folding and self-assembly properties. The resulting hybrid biomaterials form thermotropic columnar hexagonal mesophases in which the peptides adopt an α-helical conformation. Bundling of the α-helical peptides accompanies self-assembly of the peptide-dendron hybrids into cylindrical nanostructures. The bundle stoichiometry in the mesophase agrees well with the size found in solution for α-helical bundles of peptides with a similar amino acid sequence.

Peptide–dendron hybrids that adopt sequence-encoded β-sheet conformations

“…We recently reported examples of α-helix bundle-forming peptide-dendron hybrids that self-organize in an hexagonally ordered array of columns. 54 We found that the helix bundle stoichiometry in the liquid crystalline mesophase matches the stoichiometry of the bundle formed by the peptide in aqueous buffer. This remarkable correspondence implies that folding and self-assembly instructions encoded by the amino acid sequence persist in the non-biological environment of the liquid crystalline mesophase.…”

“…The same polar and non-polar residues were used in our previously reported α-helical bundle-forming peptide-dendron hybrids. 32, 33, 54, 55 The side-chain amino group of each lysine residue is efficiently acylated using dendritic pentafluorophenyl esters. 54 DeGrado and Lear have shown that a seven-residue peptide with alternating leucine and lysine residues self-assembles into a β-sheet structure in buffered aqueous solution.…”

“…32, 33, 54, 55 The side-chain amino group of each lysine residue is efficiently acylated using dendritic pentafluorophenyl esters. 54 DeGrado and Lear have shown that a seven-residue peptide with alternating leucine and lysine residues self-assembles into a β-sheet structure in buffered aqueous solution. 56 The N -terminus of the peptide was acetylated to ensure that the dendrons would be conjugated exclusively through the side-chains of the lysine residues.…”

“…The efficient amidation reaction between amines and pentafluorophenyl esters makes pentafluorophenyl esters excellent reagents for ligation of polymers with proteins 59, 60 and dendrons with peptides. 26, 54…”

“…Inspired by the tunability and processability afforded by combinations of peptides with dendrons, we have investigated hybrids of dendrons with an α-helical bundle-forming peptide. 32, 33, 54, 55 The defined arrangement of different amino acids in the core of an α-helix bundle motif could allow us to synthesize chemical gradients or unique binding sites within supramolecular dendrimers. We recently reported examples of α-helix bundle-forming peptide-dendron hybrids that self-organize in an hexagonally ordered array of columns.…”