Chemistry Reference
In-Depth Information
two) functionalised at the N-terminus with aromatic moieties. These systems
are known to give rise to a range of self-assembling structures, depending on
the balance between the aromatic p-stacking and hydrogen bonding inter-
actions between the peptide moieties. One proposed structure are the highly
stable p-p-interlocked b sheets (or p-b structures) that have been observed for a
number of these systems.
33,34
Some of the aromatic residues that have been
used in this context are phenyl, naphthyl, pyrene, 9-fluorenyl as well as the
nucleobases (Figure 4.1).
d
n
1
r
3
n
g
|
5
4.4.1.2 Enzyme Recognition Site
A range of enzymes have been utilised to initiate self-assembly including
transglutaminase,
35
a-chymotrypsin,
13
thermolysin,
36-41
subtilisin,
42,43
phos-
phatase,
44-46
trans-acylase,
47
penicillin G amidase,
48
and (a combination of)
kinase/phosphatase.
49
Herein, we will concentrate on systems that are based on
the widely used aromatic peptide amphiphiles focusing on two main categories
of chemical reactions like i) Hydrolysis (''breaking'' bonds, by enzymes such as
phosphatase, subtilisin and b-lactamase) and ii) Condensation/transacylation
(''making'' bonds, by enzymes such as thermolysin and a-chymotrypsin).
3
.
4.4.1.3 Molecular Switch Component
As mentioned, the enzyme-triggered self-assembly and associated rebalancing
of the hydrophobic/-philic parts of building blocks usually involves either
making, or breaking of covalent chemical bonds (Figure 4.2). The resulting
hydrogelator molecules often rapidly reach their critical aggregation concen-
tration at the site of catalysis, and start to self-assemble into nanofibres that
eventually entangle to form the higher-order network structure of a supra-
molecular hydrogel. For route a, the formation of the supramolecular assembly
relies on reactions that are favourable in water (hydrolysis of amides and
(phosphate) esters), giving rise to a largely irreversible system. The structural
details of these chemical conversions are shown in Figure 4.3. In route b, the
self-assembly may take place under reversible conditions if the condensation
(a)
Precursors
Enzyme
Hydrogelator
(b)
Precursors
Self-assembly
(non-covalent attachment)
Supramolecular
hydrogel
Figure 4.2
Proposed mechanism for enzyme triggered self-assembly (a) formation of
supramolecular assembly via bond cleavage (hydrolysis) (b) formation of
supramolecular assemblies via bond formation (condensation).
