"Zipper" molecular beacons: a generalized strategy to optimize the performance of activatable protease probes.
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.
Chen
Juan
J
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Liu
Tracy W B
TW
Lo
Pui-Chi
PC
Wilson
Brian C
BC
Zheng
Gang
G
D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D015335:Molecular Probes / Q000138:chemical synthesis / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000627:therapeutic use
D005456:Fluorescent Dyes; D015335:Molecular Probes; D017319:Photosensitizing Agents; D010447:Peptide Hydrolases