Introduction to Unnatural Foldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 63

Figure 2.15 Superimposition of (a) the 13/ 11-helices of a / d- and b / g-hybrid peptides, (b) the
13-helix of a / d-hybrid peptides and the native a-helix and (c) the most stable mixed 20/ 22-
helix of a / d-hybrid peptides and the gramicidin A helix. Reprinted with permission from Ref.
[55]. Copyright 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
these foldamers. Detailed structure analyses show the formation of a novel 13/11-motif
corresponding to a mixed or b-helix. The authors have also compared the conformational
properties of a/d-hybrid peptides with those of other hybrid peptides, for instance,
a/b-, a/g-andb/g-hybrid peptides (Figure 2.15). Remarkably, the most stable mixed
20/22-helix is overlapping with the structure of the gramicidin A membrane channel.
This relationship demonstrates the considerable potential for a/d-hybrid peptides to
mimic native peptide and protein structures.
2.2.5 Aliphatic Urea Foldamers
Urea, thiourea and their derivatives have been playing a central role in the field of supra-
molecular chemistry since the 1940s-1950s, when urea itself was recognized to form self-
assembled tunnel host structures, so-called urea inclusion compounds, in the presence of
appropriate guest molecules [56]. Despite receiving far less attention than their amide
counterparts, oligomers with a urea-type backbone (-[RNHCONH] n -) have gradually
made their mark in the field [57]. The urea linkage shares a number of desirable features
(i.e., rigidity, planarity, polarity and hydrogen bonding capacity) with the amide group.
However, the subtle differences between the two linkages are significant when they are
introduced in oligomers with self-assembling and/or folding propensity:
1. The dipole moment of ureas exceeds that of amides.
2. As a result of competitive conjugation, the double bond character of the CONH bond is
significantly reduced in ureas compared toamides(rotationbarriersforureasare
around 10-12 kcal mol 1 vs 16-20 kcal mol 1 for amides).
3. Due to the presence of one additional NH-group, N , N 0 -disubstituted ureas have a pro-
pensity to form three-centered H-bonds.
N , N 0 -Linked oligoureas are formally obtained by the substitution of NH for the a-CH 2
of the amino acid constituents of g-peptides. Guichard's group was been working for
several years on the synthesis and self-assembly of aromatic and aliphatic urea oligomers
[58] and have demonstrated that the urea modification are compatible with the g-peptide