Glucose-triggered self-assembly of peptide-based fluorescent probes for highly selective ratiometric detection of D-Glucose in aqueous solution at physiological pH and biological fluids

D-Glucose (Glu) is the principal source of energy production for important organs in human beings. We have first developed a monoboronic acid-based fluorescent sensor (1) for highly selective ratiometric detection of Glu among hexose in aqueous solution at physiological pH. The peptide-based probe bearing a pyrene fluorophore and a phenylboronic acid showed remarkable sensing ability for Glu such as high sensitivity for Glu, high enhancement (70-fold) of the excimer emissions, low detection limit (3.1 µM), fast response (< 10 mins), and high-water solubility. The fluorescent study of peptide-based probes (1−5) suggested that the amphiphilic peptide moiety consisting of the positively charged amino acid (Arg and Lys) and hydrophobic Trp residue played a critical role for the ratiometric response toward Glu. The binding mode study of 1 indicated that the probe formed a 2:1 complex with Glu and then the complexes self-assembled, resulting in significant enhancement of excimer emission, whereas the probe formed a 1:1 complex with Fru that did not assemble, resulting in no considerable fluorescent changes. We demonstrated that Glu induced the formation of nanoparticles and supramolecular gels of 1 depending on the concentration of the probe and Glu. 1 could quantify Glu in real urine and human serum samples by ratiometric response. This was the first example of self-assembling peptide-based probe triggered by Glu for fluorescent detection of Glu and hydrogel formation. Glu-triggered self-assembly of the peptide-based probes could be applied not only for novel sensing systems but also for the development of drug delivery and regenerative medicine.