Exploiting Biocatalysis in the Synthesis of Supramolecular Polymers - Enzymatic Polymerisation - page 130

a pentapeptide), only a few of them are found in biological systems. Consider-
able progress has been made towards elucidating design rules for peptide-based
supramolecular materials [ 42 - 45 ] . The design rules are either derived by copying
nature (

-sheet) [ 46 , 47 ] or are entirely new designs that exploit peptide
derivatives such as aliphatic [ 11 , 48 ] or aromatic peptide amphiphiles [ 10 , 49 - 52 ] .
The latter systems allow for the use of much simpler, shorter peptides (as small as
dimers) compared to other approaches that usually require at least ten amino acids
(and often many more) in each peptide chain. This approach facilitates rational
design and lowers costs for eventual application.
We focus on enzymatically controlled supramolecular polymerisations based on
aromatic peptide amphiphiles as building blocks because these are by far the most
widely studied systems. These are short peptides (generally one to five amino acids)
that are modified (usually at the N-terminus) with aromatic groups such as phenyl,
napthyl, pyrene, 9-fluorenyl methoxycarbonyl (Fmoc) etc. (Fig. 2 b , c). It was first
highlighted in the mid-1990s that certain Fmoc-dipeptides can self-assemble to form
gel-phase materials [ 53 ]. For a number of aromatic peptide amphiphiles, it has been
shown that self-assembly is governed by formation of in-register antiparallel

α -helix, β

-sheet
structures with aromatic groups extended at both termini of each sheet. Multiple
sheets were found to lock together via (antiparallel)

β

π -stacking interactions to give

rise to structures (Fig. 3 ) [ 51 , 54 ]. The nature of the

amino acid residues in these systems dictates the curvature of the

π -interlocked β -sheets or π - β

β -sheets, and in

cases where curvature allows both edges of an array of -sheets to lock together fi-

bres or hollow tubes may form [ 21 , 22 ] . It is clear that the morphologies and the
dimensions of these nanostructures are strongly dependent on the route of self-
assembly (see Sect. 3.3 ) as well as on the amino acid sequence and the chemical
nature of the aromatic residues in the building blocks.

β

a

b

iii

i

OH
OH

OH

O P =O

O R 1 O R 1 O R 3

O

R 2 O

Phosphatase OH Protease NH OR 4

O N

OH

Ar N

H

N
H

Ar Ar N

H

N
H

H 2 N

+

OR 4

OH

Ar O O R 2 O

N
H

O

O R 2

O

7

5 6

2

1

ii

H
N

O R 1 O O R 1 O

H
N

Esterase

O

Ar = OR OR Ar N

H

Ar OH

OR

H

O R 2

O R 2

3 4

Fig. 3 Mechanisms for enzymatic supramolecular polymerisation: ( a ) Formation of supramolec-
ular assembly via bond cleavage. ( b ) Formation of supramolecular assemblies via bond formation.
Examples are shown of biocatalytic supramolecular polymerisation of aromatic peptide am-
phiphiles via (i) phosphate ester hydrolysis, (ii) alkyl ester hydrolysis, and (iii) amide condensation
or reversed hydrolysis using protease