Chemistry Reference
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Figure 11.35 Helical conformational equilibria of dendron-modified alanine residue (A
D
)
within a peptide-dendron conjugate. Peptide-dendron sequences are shown in the table form.
were studied (Shao et al. 2007). Interdendron spacing along the peptide backbone was
progressively increased from i, i
þ
4toi, i
þ
11 (Fig. 11.35).
Such polyalanine sequences generally display a high propensity to adopt an
a-helical conformation, even in aqueous media. The majority of the peptide-
dendrons exhibited a-helical/random coil conformations in water and tetrafluor-
oethylene (TFE) with slightly lower helicity compared with a control peptide
lacking dendron side chains. These peptides did not exhibit any evidence for
peptide-dendron coupled equilibria in the form of a helical bias in the dendron.
An a-helix to b-sheet conformational transition occurred in water for two of the
peptide-dendron conjugates: (i, i
þ
6) and (i, i
þ
10). Strong chiral transfer from
the peptide backbone to the dendron emerged exclusively in the b-sheet forms of
(i, i
þ
6) and (i, i
þ
10), revealing a synergistic coupling of the conformations of
both structural elements. Atomic force microscopy (AFM) of both peptides revealed
amyloid-like nanofibrils in PBS buffer at 10 mM, whereas in 60% TFE/PBS globular
aggregates were observed (Fig. 11.36). In addition, (i, i
þ
6) forms a hydrogel in
water at concentrations as low as 1.7 mM.
These studies support the notion that the occurrence of coupled conformational
equilibria between the peptide and dendron structures requires peptide folding to
be strongly coupled with dendron packing. Satisfying this criterion ensures that the
peptide secondary structure is stabilized by dendron packing; further, this packing
concomitantly promotes interdendron motions that amplify helical biases. It is note-
worthy that the peptide-dendrons exhibiting a lower a-helicity, relative to the
control, lack evidence for peptide to dendron chiral communication. In contrast,
the two sequences that exhibit b-sheet conformations exhibit strongly coupled
