Chemistry Reference
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Figure 14.11 (Left) The molecular structure of collagen fragments used as building blocks
and (right) the TEM image of self-assembled fragments. Reprinted from Kotch and Raines
(2006). Copyright 2006 National Academy of Sciences.
noted in the previous example. This group went a step further and tested the length
and thermal stability in aqueous methanol, in which more stable triple helices con-
taining Hyp residues produced longer fibers. The collagen building blocks and the
product of their assembly are shown in Figure 14.11.
Recently, Cejas and coworkers (2007) investigated the self-assembly of short
peptides with Gly-Pro-Hyp repeating units containing hydrophobic end groups,
containing phenyl, pentafluorophenyl, or isopropyl groups. The aromatic end
groups were of interest because of potential p-pstacking noncovalent interactions,
which could provide a potential driving force for head-tail self-assembly.
Computational molecular modeling of the self-assembly process between two
triple helices predicted face-face orientations of the end groups, which result in
strong binding between the aromatic groups, especially for pentafluorophenyl/
phenyl pairs, but not for the isopropyl group. The thermal stability of the peptide
was studied by CD and NMR, which confirmed its triple helicity at well above
room temperature. A newly prepared solution of peptide containing a pentafluoro-
phenyl end group formed a mixture of small (3 nm) and large (190 nm) particles,
which aggregated to form fiberlike material that was microns in length and had a
0.26 mm average diameter within 24 h. The peptide was assessed in a human platelet
assay and was found to induce platelet aggregation similar to equine type I collagen.
In the previous examples, short collagen-like peptides were designed to
have complementary binding sites that led to propagation of self-assembly to
form large triple helical fibers or aggregates. The next two examples describe self-
assembly of collagen-like peptides with the help of covalent
linking of short
collagen-like segments.
The work of Kishimoto and cohorts (2005) focused on the synthesis of a high
molecular weight collagen-like polypeptide by the direct polycondensation of the
collagen characteristic sequence (Pro-Hyp-Gly)
n
(n ΒΌ 1, 5, and 10) using 1-ethyl-3-
(3-dimethyl-aminopropyl)-carbodiimide hydrochloride and 1-hydroxybenzotriazole
(HOBt). Carbodiimides and HOBt are commonly used coupling reagents in peptide
synthesis. The polymerization reaction creates long triple helical chains from short
peptides through head-tail propagation. No side reactions were observed by FTIR
and
1
H-NMR of poly(Pro-Hyp-Gly)
10
. Various concentrations of peptide monomers
