Chemistry Reference
In-Depth Information
loss of control over the assembly process. Most important in this category are the
family of amyloid fibers formed from relatively short peptides aggregated into
extended b-sheet nanofibers. Regardless of their healthy or diseased source, these
fibers variously illustrate the desirable features of controlled assembly, controlled dis-
assembly, nanostructured dimensions, atomically precise localization of chemical
functionality, and fiber directionality. All of these features are extremely desirable
materials properties. Mimicking these natural examples will help us to understand
Nature in more detail and will result in sophisticated new nanostructured materials.
This chapter examines some of the exciting results in nanofiber self-assembly (supra-
molecular polymerization) that have been described in the past decade utilizing pep-
tides and peptide derivatives as their building blocks. The chapter is divided by the
underlying peptide architecture used to make the fibers: a-helix, parallel and anti-
parallel b-sheets, and collagen-like polyproline type II (Table 14.1).
14.2. SELF-ASSEMBLY OF NANOFIBERS BASED ON
a
-HELICES
a-Helical coiled coils are one of the most common protein structural motifs in Nature.
They are utilized to generate higher ordered tertiary and quaternary protein structures
or act as recognition elements between two proteins. Because of this ubiquity in
Nature, they have been studied intensively and are now one of the few protein
motifs for which amino acid sequences can be selected and synthesized that will
result in predetermined three-dimensional (3-D) structures.
A single a-helical molecule is stabilized by the intramolecular hydrogen bonding
between the (i) and (i
þ
4) residue along the peptide backbone, allowing for the for-
mation of a right-handed helix with 3.6 amino acids per turn. However, a lone helix is
rare. Typically, the helix must be stabilized by interactions with other portions of the
protein or, in the case of coiled coils, it may be stabilized by interactions with
additional helices.
The resulting structure largely depends on the amphiphilic pattern of the protein
primary sequence comprising a variety of hydrophobic and polar residues. If a
helix peptide molecule is designed to have all of the polar residues on one face
and all of the hydrophobic residues on the other, a specific type of protein tertiary
structure can be created with two or more helix chains associated together through
hydrophobic interaction to form a coiled coil. The coiled coil was first postulated
in 1953 by Crick to explain the X-ray diffraction pattern of a-keratin (Crick 1953).
Later it was identified in many natural proteins, including a yeast transcription
factor, GCN4 protein, that has been considered, because the X-ray crystal structure
has been determined as a parallel coiled coil dimer, as an excellent model system
to study protein-protein interactions (O'Shea et al. 1991). The primary sequence
of GCN4 (also known as a “leucine zipper”) demonstrated a distribution of hydro-
phobic and polar amino acids along the peptide backbone characterized by a
seven-residue repeating unit called a heptad repeat, which is denoted abcdefg.
Many reports (Hodges 1996; Lupas 1997; Oakley and Hollenbeck 2001) have docu-
mented the structural features of coiled coils. In order to pattern a peptide into a coiled
