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()
n
O
N
H
O
()
n
O
O
O
()
n
N
N
H
()
n
N
H
dibenzofuran
2,2'-substituted biphenyl
2, 3'-substituted biphenyl
diphenylacetylene
O
O
O
O
HN
N
X
N
N
H
H
O
O
N
N
O
X
O
O
O
N
O
N
N
H
HN
X
=
CH
2
: Nip-D-Nip
X
=
O: di-oxaNip
HN
type VI
-turn mimic
β
Pro-D-Pro
diketopiperazine
Figure 3.26 Examples of aromatic-based and proline-based b-sheet nucleating
templates
2,2
0
-substituted biphenyls were developed by Feigel as turn mimics in
cyclic peptides [218]. The analogue with
n ¼
2 was recently shown to be
capable of adopting an intramolecularly hydrogen-bonded turn confor-
mation, in contrast to the shorter-chain (
n
<
2) analogues [219]. The
stability of the hairpin conformation induced by the 2-amino-2
0
-carboxy-
diphenylacetylene scaffold was shown to depend on the relative config-
uration of the appended peptide strands [220,221].
Amino acids conjugated to the indolizidinone type VI b-turn mimic
were shown to form interstrand hydrogen bonds, with a strong depen-
dence on the sequence [222]. The bis-proline-derived diketopiperazine
scaffold induces an extended conformation in a cyclic peptide containing
the NPNA motif, which elicited antisera in mice against
P. falciparum
sporozoites [223]. The heterochiral dipeptide sequence
L
-Pro-
D
-Pro and
the di-b-amino acid segment (R)-nipecotic-(S)-nipecotic acid (Nip-Nip)
were more recently shown by Marshall and Gelman, respectively, to be
very efficient turn inducers [224,225]. The dioxanipecotic acid (X
¼
O)
segment was shown to lead to even more stable turn motifs than the
dinipecotic acid (X
¼
CH
2
) segment [226].
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