title: "Zipper" molecular beacons: a generalized strategy to optimize the performance of activatable protease probes.
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.
authors.affiliation: Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Tracy W B
authors.initials: TW
authors.lastname: Liu
authors.forename: Pui-Chi
authors.initials: PC
authors.lastname: Lo
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: 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
chemical_list: D005456:Fluorescent Dyes; D015335:Molecular Probes; D017319:Photosensitizing Agents; D010447:Peptide Hydrolases