Biomedical Engineering Reference
In-Depth Information
2.2 Metalloreceptor Scaffolds in Differential Sensing
An emerging field within coordination chemistry is the use of synthetic metallo-
receptors in array formats for the detection of small and large biomolecules. The
biological processes of olfaction and taste, which use “differential” receptors biased
toward specific classes of analytes, provide inspiration for this work. In contrast to
traditional “lock-and-key” approaches aimed at identifying highly selective
receptor-analyte interactions, each arrayed receptor for differential sensing is
designed to be cross-reactive with diverse affinities for different targets of interest [
17
].
As a result, specific analytes and analyte mixtures produce fingerprint responses that can
be extracted as unique diagnostic patterns using optical or chemometric tools. Synthetic
receptor arrays are an exciting frontier in sensor development with applications in the
detection of bioanalytes, pathogens in solution, environmental analysis, and medical
diagnostics. While transition metal cores are not critical to the construction of such
differential sensing receptor arrays, these subunits offer the potential advantage of target
coordination over alternate covalent systems.
For example, Anslyn and coworkers [
18
] have designed a series of metalated
synthetic receptor arrays as differential sensing platforms for a range of bioanalytes.
A homogeneous array sensing scheme for the differentiation of small peptides and
their phosphorylated analogues is shown in Fig.
3
[
19
]. Synthetic tripeptides
derived from the amino acid sequence flanking Ser-129 of filamentous
-synuclein,
a site of phosphorylation implicated in Parkinson's Disease, were used as model
analytes to assess the discriminatory properties of the differential receptors for
detecting protein phosphorylation. The platform involves a series of receptors
created by appending two random peptide sequences to a central
C
3v
-symmetric
metal complex core unit that selectively binds tetrahedral anions such as
monophosphate esters. Using a combination of different metal ions and indicator
dyes, receptors were screened optically for analyte binding using colorimetric/
fluorescent indicator displacement protocols [
20
]. Patterns within the optical data
sets were identified using pattern recognition algorithms.
A tris-[(2-pyridyl)methyl]amine core ligand subunit was selected due to its well-
known capacity for binding several transition metals. Coordination of Cu(II) to this
ligand framework substituted with guanidinium groups had previously been shown
to produce a selective binding pocket for phosphate over other anions with different
sizes, shapes, and charge [
21
,
22
]. The high affinities reported for phosphate were
proposed to proceed through a combination of ion-pairing interactions between
guanidiniums and the Cu(II) center with the oxygens of the tetrahedral anion. This
general ligand framework was functionalized with random tripeptide sequences via
solid-phase synthesis to impart differential cross-reactivity toward the target
peptides. Five different peptide side chains, three transition metal ions [Cu(II),
Ni(II), Co(II)], and three indicator dyes were selected through extensive screening
to produce an array of 45 receptor/metal/indicator combinations. Using linear
discriminate analysis of the differential optical responses, 100% classification of
the six peptide targets was achieved. Importantly, this general detection scheme
a
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