Pools of free zinc ion have been found in a variety of intra- and extracellular environments, often linked to signaling events in living organisms. Disrupted patterns of zinc accumulation have been associated with diabetes, cancer, and neurodegenerative diseases such as Alzheimer's disease;nevertheless, the specific role of this ion in such pathological process and in a range of physiological functions remains poorly understood. The development of better imaging techniques that allow for the study of free Zn2+ in a wide range of biological samples is crucial in solving many of the unanswered questions about zinc biology. The research proposal outlined herein focuses on the design and development of new fluorescent probes for the detection of free Zn2+ in biological samples, producing an optical response in the Near-Infrared region of the electromagnetic spectrum. The proposed strategy is based on the modulation of the Near-Infrared fluorescence properties of Single-Walled Carbon Nan tubes (SWCNT), taking advantage of conformational changes of oligonucleotide conjugates adsorbed to the tube's walls. Synthetic nucleotides, specifically designed to chelate Zn2+, are incorporated into oligonucleotide sequences in order to confer zinc-specific binding capabilities to the SWCNT-oligonucleotide complex. The choice of fluorophore (SWCNT) and zinc- binding moiety seeks to address an important and thus far unsolved challenge in mobile Zn2+ imaging: the tuning of the sensor's optical response to a spectral window more suitable for in vivo applications, with less background interference, higher tissue penetration, and less damage to cellular components.
| Buccella, Daniela; Horowitz, Joshua A; Lippard, Stephen J (2011) Understanding zinc quantification with existing and advanced ditopic fluorescent Zinpyr sensors. J Am Chem Soc 133:4101-14 |
