C O M M U N I C A T I O N S
structural elements; for example, the choline substrate could be
replaced with other compounds that can be oxidized to produce
hydrogen peroxide, thereby allowing the application of other
oxidases in the DCR assay. In principle, any analyte of interest
that has cleavage reactivity toward a specific trigger could be
incorporated collectively with the specific triggering group in the
dendritic platform.
In conclusion, we have demonstrated a novel technique for signal
amplification that, like immuno-PCR, takes advantage of exponen-
tial growth. The amplification is based on a distinctive dendritic
chain reaction that progresses through a growing number of
diagnostic cycles. This is the first example of exponential signal
amplification for diagnostic purposes that is not based on PCR and
can be performed under aqueous conditions. When coupled with
an additional probe activity, this technique could be applied for
detection of other analytes. Optimization of the aqueous stability
of the probe with respect to spontaneous hydrolysis while maintain-
ing a rapid disassembly rate upon reaction with the analyte should
significantly increase the sensitivity of the DCR technique.
Acknowledgment. D.S. thanks the Israel Science Foundation
(ISF) and the Binational Science Foundation (BSF) for financial
support. Special thanks go to Prof. Ehud Gazit, Prof. Dave Segal,
and Prof. Moshe Portnoy for helpful discussions.
Supporting Information Available: Full experimental details and
characterization data for all new compounds. This material is available
Figure 5. Diagnostic assay for detection of PGA through coupling with a
DCR probe. (A) Release of 4-nitroaniline from dendron 3 (500 µM) in the
presence of COX (0.3 mg/mL) and probe 4 (500 µM) in PBS at pH 7.4
monitored at 405 nm over a range of PGA concentrations. (B) Comparison
of the signal measured in the presence of COX by the DCR amplification
technique (green) vs that measured using phenylacetamide directly attached
to 4-nitroaniline (blue) at 30 min. The values shown were obtained by
subtracting the background at 30 min.
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