Chemistry Reference
In-Depth Information
The dimension of the resultant structure was visualized by atomic force microscopy
(AFM). Indeed, the width of the fibers was reduced compared to that of SAF pep-
tides; however, its length was much more heterogeneous. Most fibers were also
shown to be shorter than that of previously described coiled coil nanofibers. Fiber
shortening could be related to the 1) weak association between sticky-ended coiled
coils and 2) salt effects. It was found that sodium chloride and ammonium sulfate
have a distinct effect on the fibril lateral aggregation, leading to short fibers in
NaCl and long fibers in ammonium sulfate.
Although the coiled coil stands out as the most common building block in the
design of helical nanofibers, other types of helix motifs have also been engineered
into self-assembled nanostructures. One example is the helix-turn-helix peptide
developed by Meredith's group (Lazar et al. 2005). The primary sequence is
derived from apolipoprotein I containing multiple amphiphilic helical fragments con-
nected by turns. The ability of peptides to self-assemble into fibrils was found to
depend on the rigidity and structural organization in the turn region. As characterized
by CD, FTIR, and X-ray diffraction, the self-assembled fibers were confirmed to be in
an a-helical pattern. X-ray diffraction also indicated that the helical axis is perpen-
dicular to the fiber long axis, which is very unusual for helix-based nanofibers
and differed from all the mentioned self-assembling helical nanofibers having
helices parallel to the fiber axis.
Unlike the conventional heptad motif based coiled coil peptides, Frost et al. (2005)
designed a series of amphipathic helical peptides (KIA peptides) that have a consen-
sus sequence of AKAxAAxxKAxAAxxKAGGY where two x positions out of six are
occupied by Ala and the rest by Ile. These peptides were created in an attempt to
mimic the ridges into grooves packing that has been utilized by many natural proteins
(Chothia et al. 1981). A combinatorial library containing 15 short peptides was con-
structed by varying the location of Ala and Ile. These peptides distinguished them-
selves from one another in the hydrophobic interface, which in turn affected their
folding pattern. Among the 15 peptides, only 2 formed insoluble helical filaments
(at a high salt concentration, used to screen the charges between lysine residues).
Fiber formation could be reversed by either reducing the salt concentration or
through the addition of another peptide (KIA16).
In spite of the great advances in the construction of helix-based nanofibers over the
last decade, the application of these materials still remains a large area to explore. A
key challenge is to engineer chemical and mechanical stability into the resultant nano-
fiber scaffold that is important for 3-D cell culture. In this regard, Woolfson's group
has taken the first step in targeting the construction of helical nanofibers with tunable
thermal stability and nanoscale order (Smith et al. 2006). Potekhin and colleagues
(2001) have proven the possibility of attaching a noncoiled coil moiety at the
N-terminus of the originally designed aFFP without disrupting fibril formation.
This study will encourage development of fibrous scaffolds with incorporation of a
variety of biologically active ligands and perhaps other electronically active moieties
imparting special electronic and transmitter ability to the “peptide wire.” Although
in vitro experiments using coiled coil based nanofiber scaffolds are rare, results
from Corradin's group are promising in terms of the higher efficiency in promoting
