Because of their potential for nondestructive detection and cell permeability, fluorescent chemosensors for carbohydrates can play a critical role in glycobiology. The objectives of this continuing research program involve the application of molecular clefts as fluorogenic sensors suitable for biological studies of monosaccharides and carbohydrate derivatives. The scope of these investigations build on previous results in which novel signal transduction mechanisms were identified and shown to proceed by substituent changes of the fluorophore component. In an effort to significantly augment the fluorescence signal intensity over conventional Photoinduced Electron Transfer (PET) fluorescence as well as red-shift this response to longer wavelength emission, new sensors are proposed which utilize Resonance Energy Transfer fluorescence (FRET). This research plan begins by investigating intermolecular energy transfer between two donor/acceptor Forster-pairs. Given the calculated distance of separation (14 Angstroms) for one saccharide complexed between two receptor components, well known donor/acceptor dyes that coincide with this Forster distance such as diethylaminocoumarin and fluorescein are incorporated into the sensor design. Subsequent plans utilize rigid aromatic diimide chromophores as non-fluorescent molecular scaffolds to which recognition groups are appended via benzyl-imide bonds. Cooperative binding of analyte between receptor sites is expected to decrease torsional motion and enhance energy transfer rates between coupled FRET cassettes. In addition to investigating simple monosaccharides via FRET based sensors, carbohydrate derivatives relevant to glucose metabolism and cell membrane carbohydrates are also targeted for fluorimetric detection. Specifically, glucose-6-phosphate and N-acetylneuraminic acid via 2-point bifunctional binding sites from phenylboronic acid and guanidinium receptors. Second messenger myo-Inositol-triphosphate via bis- guanidinium groups and glucosamine sensing through crown-ether coordination are also included in these fluorometry studies.
| Paudel, Sangita; Nandhikonda, Premchendar; Heagy, Michael D (2009) A comparative study into two dual fluorescent mechanisms via positional isomers of N-hydroxyarene-1,8-naphthalimides. J Fluoresc 19:681-91 |
| Cao, Zhi; Nandhikonda, Premchendar; Heagy, Michael D (2009) Highly water-soluble monoboronic acid probes that show optical sensitivity to glucose based on 4-sulfo-1,8-naphthalic anhydride. J Org Chem 74:3544-6 |
| Cao, Haishi; McGill, Tom; Heagy, Michael D (2004) Substituent effects on monoboronic acid sensors for saccharides based on N-phenyl-1,8-naphthalenedicarboximides. J Org Chem 69:2959-66 |
