Chemistry Reference
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Deechongkit et al. 2005). Extensive TEM studies have shown nanofiber formation
with distinct morphology (protofibril, twisted fibers, ribbons, lateral associated
fibers, etc.) under different sample preparation conditions. The polymorphorism
observed in this system has a general significance in understanding the mechanism
of protein misfolding that causes many types of neurodegenerative diseases.
Banerjee's group established a series of tripeptides differing with each other in the
C- or N-terminal protecting group that coordinated peptides to self-assemble into
entangled nanofibers composed of antiparallel b-sheets (Das et al. 2004; Maji
et al. 2004; Ray, Das et al. 2006; Das et al. 2007). The gelation property was exam-
ined in water and a variety of organic solvents by differential scanning calorimetry,
TEM, FTIR, single crystal X-ray, and X-ray powder diffraction methods, showing
the ability of terminal functionality to alter peptide's gelation properties. The Gazit
group reported the formation of peptide nanotubes made of short b-sheet forming
dipeptides (Phe-Phe; Reches and Gazit 2003). Other dipeptides (Phe-Trp, Trp-Tyr,
Trp-Phe, and Trp-Trp) have also been examined, but none of them showed tubular
structures as the primary nanostructures. In contrast, this observation indicates that
the specific packing of aromatic residues often found in natural amyloids plays a sig-
nificant role in the self-assembly of amyloid fibrils. Short peptides comprising b, d,
and vamino acids have been reported by several groups in the construction of supra-
molecular self-assembling structures (Banerjee et al. 2005; Dutt et al. 2005; Martinek
et al. 2006). Despite the challenge in the synthesis of peptides containing noncano-
nical amino acids, the distinct secondary structures displayed by these peptides from
the commonly seen aamino acid peptides will create a diverse self-assembly pattern
and supramolecular nanostructural morphology.
14.3.4. Parallel
b
-Sheet Nanofibers
Although the majority of b-sheet forming nanofibers adopt an antiparallel orientation
because of the preferred orientation of hydrogen bonding between peptide backbone
amide linkages, b-sheets can be stabilized in parallel fashion by rational covalent
attachment of the hydrophobic domain at the N- or C-terminus. In 2001 a new
class of self-assembling molecules known as peptide amphiphiles (PAs) was deve-
loped by the Stupp group (Hartgerink et al. 2001), featuring a long hydrophobic
aliphatic chain at the N-terminus of a hydrophilic peptide. This simple modification
creates an amphiphilic molecule with a propensity to form cylindrical micelles
(nanofibers) in aqueous solution. In addition to the amphiphilicity, the stability of
the self-assembled structure comes from b-sheets like intermolecular hydrogen
bonding in the peptide region, especially those formed by the four amino acid
residues closest to the nanofiber core (Paramonov et al. 2006). Spherical, not cylind-
rical, micelles were observed when the hydrogen bond network was eliminated, for
example, through the incorporation of N-methylated residues. Peptides with tails
attached to the same terminus form parallel b-sheet.
The nanofibers formed by PAs are microns long and have a uniform diameter of
approximately 6-8 nm, depending on the length of the PA molecule. Self-assembly
of the nanofibers can be controlled by pH adjustment and/or addition of divalent
