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"Zipper" molecular beacons: a generalized strategy to optimize the performance of activatable protease probes
Juan Chen1, Tracy W B Liu, Pui-Chi Lo
1Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Abstract:
We report the proof-of-principle concept for zipper molecular beacons (ZMB) comprising an asymmetrical polyarginine/polyglutamate electrostatic "zipper" hairpin-linked fluorophore-quencher pair. The objective is to balance maximal quenching efficiency and optimal two-step activation (protease cleavage/zipper dissociation), while enhancing target cell uptake. This strategy also eliminates the peptide sequence dependence of conventional protease beacons. This ZMB concept is a generalizable approach to improve the functionality of a wide range of diagnostic/therapeutic probes through a simple switching of substrate sequences.
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