Chen J, Liu TWB, Wilson BC & Zheng G
Bioconjugate Chemistry, 2009

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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