title: Chiral, J-Aggregate-Forming Dyes for Alternative Signal Modulation Mechanisms in Self-Immolative Enzyme-Activatable Optical Probes.
abstract: Enzyme-activatable optical probes are important for future advances in cancer imaging, but may easily suffer from low signal-to-background ratios unless not optimized. To address this shortcoming, numerous mechanisms to modulate the fluorescence signal have been explored. We report herein newly synthesized probes based on self-immolative linkers containing chiral J-aggregate-forming dyes. Signal modulation by formation of chiral J-aggregates is yet unexplored in optical enzyme probe design. The comprehensive characterization of the probes by absorption, CD, fluorescence, and time-resolved fluorescence spectroscopy revealed dye-dye interactions not observed for the free dyes in solution as well as dye-protein interactions with the enzyme. This suggested that J-aggregate formation is challenging to achieve with current probe design and that interactions of the dyes with the enzyme may interfere with achieving high signal-to-background ratios. The detailed understanding of the interactions provided herein provides valuable guidelines for the future design of similar probes.
authors.affiliation: BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Strasse 11, 12489 Berlin, Germany.
authors.forename: Jagoda
authors.initials: J
authors.lastname: Sloniec-Myszk
authors.affiliation: BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Strasse 11, 12489 Berlin, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Resch-Genger
authors.affiliation: BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Strasse 11, 12489 Berlin, Germany.|Department of Life Sciences and Chemistry, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hennig
mesh_terms: D002942:Circular Dichroism; D004396:Coloring Agents / Q000737:chemistry*; D004798:Enzymes / Q000737:chemistry*; D015335:Molecular Probes / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
chemical_list: D004396:Coloring Agents; D004798:Enzymes; D015335:Molecular Probes