Zinc-Chelating Ratiometric Fluorescent Probes

A Novel Class of Zinc-Chelating Ratiometric Fluorescent Probes NU 2003-054 Inventors Masayasu Taki Thomas O'Halloran Abstract Investigators at Northwestern University have synthesized a new class of zinc-chelating probes that are useful as ratiometric probes for zinc (Zn(II)). The probes of this invention incorporate 2-(2'-hydroxypheny) benzooxazole (HBO) as a fluorophore with an aminomethyl pyridine moiety, to bind heavy metal ions selectively. Probes of this family are effective probes to measure zinc concentration in physiological solutions, as the absorption spectra of these indicators shift upon zinc binding. The probes may be utilized in the investigation of the functions of zinc in a variety of biological systems. For example, the importance of zinc is exemplified in the requirement for zinc in the folding of the DNA-binding domains of eukaryotic transcription factors, including the zinc finger transcription factors and the large family of hormone receptor proteins. Similar functions are also expected for zinc found in the RNA polymerases and the zinc-containing accessory proteins involved in nucleic acid replication. The involvement of zinc in the activity of so many proteins demonstrates the need for tools that can be used to quantitatively and qualitatively measure zinc. Such tools will help reveal the catalytic, structural, and regulatory functions of zinc in these proteins and in turn elucidate zinc's impact on metabolism, gene expression, and signal transduction, including neurotransmission. While the inorganic physiology of intracellular zinc is poorly understood, its importance is emerging in understanding a variety of disorders in humans. Histochemical studies of mammalian tissues including the prostate, the insulin secreting beta cells of pancreatic islets, and the dentate neurons of the hippocampus reveal patterns of Zn(II) accumulation that are disrupted in some types of prostatic cancer, diabetes and neurodegenerative disorders respectively. Applications o Zinc studies in biological systems o Histochemical studies of mammalian tissues Advantages o Selective binding to heavy metal ions o Effective at measuring zinc concentration in physiological solutions IP Status Issued U.S. Patent No. 7,105,680 Marketing Contact Michael Moore, PhD Invention Manager (e) [email protected] (p) 847.491.4645