Biomedical Engineering Reference
In-Depth Information
Pre-gelator
Gelator
SAFIN
(Soluble)
Enzyme-
mediated lysis
Self-assembly
Two pre-gelator
components
SAFIN
Gelator
(Soluble)
Enzyme-mediated
coupling
Self-assembly
Figure 1.28
Cartoon representation of enzyme-mediated fiber formation. (a) A solubiliz-
ing group (red circle) is enzymatically cleaved from a pre-gelator; the resulting decrease in
solubility of the product (green oval) results in
SAFIN
formation. (b) Two soluble gelator
precursors are linked via an enzyme-catalyzed reaction, yielding an
LMOG
.
O
Opaque gel
O
OH
P
OH
HO
O
O
1. Na
2
CO
3
, buffer
2. alkaline phosphatase
OH
OH
O
N
H
O
H
O
O
45
46
1
μ
m
Figure 1.29
Fmoc-(
O
-phospho)-tyrosine
(
45
) is converted to the hydrogelator Fmoc-
tyrosine (
46
) via an alkaline phosphatase-
catalyzed dephosphorylation. The image
shows a scanning electron micrograph of the
dehydrated gel fibers. Reprinted with permis-
sion from Ref. [103a]. Copyright 2004 Wiley.
The phosphate group (which is ionic in the basic conditions of the experiment)
renders
45
soluble in water; its removal yields a product with significantly lower
solubility (
46
) that subsequently self-assembles into a fibrous aggregate, producing
a
and Fmoc-protected lysine
(not shown) yields a clear hydrogel under similar conditions. Gels produced by
this method are responsive to a range of stimuli, including temperature and pH,
allowing several experimental variables to control reversibly the gel-sol transition.
The Xu group has been a
tour de force
in this area over the last decade. A notable
development was reported in 2006: reversible gelation of a pentapeptide derivative
was controlled by a pair of enzymes that install (
SAFIN
as part of an opaque hydrogel. A mixture of
45
)a
phosphate group [104]. Addition of a kinase enzyme to the hydrogel in the presence
of ATP converts the tyrosine into a tyrosine phosphate (∼46% conversion), thus
destroying the gel. The reverse reaction, phosphatase-mediated dephosphorylation
(
47
→
48
) or remove (
48
→
47
99% conversion) triggered gel formation (Figure 1.30). Furthermore, subcuta-
neous injection of the soluble phosphorylated form of the compound into a mouse
∼
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