Biomedical Engineering Reference
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molecules containing substituent(s) that have the greatest potential to initiate
boronate ester formation was key in designing a signaling component that would
perform with the desired glucose binding characteristics.
Our preliminary efforts in designing a boronic acid sensing system focused on
selecting commercially available boronic acids with a diversity of substituent(s)
about the phenylboronic acid substructure and a reactive group that could be used
for coupling the boronic acid to a carrier scaffold. We selected phenylboronic acid
molecules whose substituent type(s) and location(s) would increase the electrophi-
licity of the boronic acid group, reducing its p
K
a
and ultimately, increasing the
binding affinity at neutral pH. The resulting boronic acid constructs, each of which
possessed unique functionalities and enabled a diversity of saccharide binding
sensitivities and selectivities, formed the basis of our library of candidate DBA
signaling component materials.
3.1.2 Dendrimers as Synthetic Receptor Scaffold Materials
Three main considerations influenced the design of the DBA scaffold. These
included: (1) selection of the appropriate scaffold to arrange the recognition motif
in the correct orientation to support binding affinity and specificity, (2) selection of
a scaffold with a mass sufficient to create a differential with glucose in order to
generate a detectable signal, and (3) selection of a construct of appropriate size to
prevent the signaling/competition component from diffusing out of the sensing
system compartment.
Owing to their physical and chemical properties, dendrimers are advantageous
for the construction of synthetic receptor materials and stable sensing applications
[
91
]. Dendrimers have a spherical and highly branched 3-D architecture that gives
them a well-defined composition and topology [
92
,
93
]. These characteristics,
combined with their high-density surface functional group capacity for boronic
acid immobilization, give dendrimers desirable physical, chemical, and
polyvalency characteristics [
91
,
94
]. Their highly functionalized terminal surfaces
also allow for control over the display of surface recognition elements. In addition,
dendrimers are frequently exploited in physiological systems because they are
water soluble, biocompatible and non-immunogenic [
92
,
95
,
96
]. They are com-
mercially available in a number of different generations and have size and mass
characteristics that are compatible with our sensing system and implantable device
design.
These characteristics make dendrimers ideally suited as scaffolds for the DBA
competition/signaling component. They simultaneously provide a water soluble,
stable, and polyvalent scaffold that facilitates and stabilizes the conjugation of the
otherwise insoluble and unstable boronic acid recognition moieties at the dendrimer
surface.
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