title: Systematic study of protein detection mechanism of self-assembling 19F NMR/MRI nanoprobes toward rational design and improved sensitivity.
abstract: (19)F NMR/MRI probe is expected to be a powerful tool for selective sensing of biologically active agents owing to its high sensitivity and no background signals in live bodies. We have recently reported a unique supramolecular strategy for specific protein detection using a protein ligand-tethered self-assembling (19)F probe. This method is based on a recognition-driven disassembly of the nanoprobes, which induced a clear turn-on signal of (19)F NMR/MRI. In the present study, we conducted a systematic investigation of the relationship between structure and properties of the probe to elucidate the mechanism of this turn-on (19)F NMR sensing in detail. Newly synthesized (19)F probes showed three distinct behaviors in response to the target protein: off/on, always-on, and always-off modes. We clearly demonstrated that these differences in protein response could be explained by differences in the stability of the probe aggregates and that "moderate stability" of the aggregates produced an ideal turn-on response in protein detection. We also successfully controlled the aggregate stability by changing the hydrophobicity/hydrophilicity balance of the probes. The detailed understanding of the detection mechanism allowed us to rationally design a turn-on (19)F NMR probe with improved sensitivity, giving a higher image intensity for the target protein in (19)F MRI.
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takaoka
authors.forename: Keishi
authors.initials: K
authors.lastname: Kiminami
authors.forename: Keigo
authors.initials: K
authors.lastname: Mizusawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Matsuo
authors.forename: Michiko
authors.initials: M
authors.lastname: Narazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuda
authors.forename: Itaru
authors.initials: I
authors.lastname: Hamachi
mesh_terms: D024401:Carbonic Anhydrase I / Q000032:analysis* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry; D017155:Wettability
chemical_list: D005456:Fluorescent Dyes; D014867:Water; D005461:Fluorine; D024401:Carbonic Anhydrase I