Preparation of New Long Wavelength Fluorescent Dyes

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DESCRIPTION (provided by applicant): Novel fluorescent dyes that operate in the long visible / near infra-red (NIR) region of the electromagnetic spectrum have been shown to act as excellent reporter components of such targeting molecular probes and tracers. Such dyes are in very short supply at the present time and those that are commercially available are very expensive or are only available under severely restrictive license agreements. Many of the available dyes have undesirable properties such as relatively high non-specific binding and a tendency to aggregate and are prohibitively expensive due in part to unoptimized synthetic methods. The main focus of this application is to discover novel, long wavelength near-infrared extended squaraine dyes by novel combinatorial chemistry techniques that are designed for use in high throughput screening, fluorescence polarization, biomedical imaging and other applicable techniques such as immunofluorescence microscopy and fluorescence activated cell sorting and counting. Novel solid phase synthetic pathways will be developed that will allow gram-scale synthesis of the dyes in high purity and will result in products that will be more widely available to the research and scientific community. There are 8 specific aims: Specific Aim 1: To Synthesize a Further 240 Novel Longer Wavelength / Near-Infrared Extended Squaraine Dyes By Using The Synthetic Methodologies Developed In Phase I. Specific Aim 2: Small Scale Purification and Characterization of the New Dyes. Specific Aim 3: Scale up Synthesis of 20 Selected Cyanine Dyes from Aims 1 and 2. Aim 4: Fluorescence Polarization (FP) Studies. Specific Aim 5: To Assess the Performance of the New Dyes in Fluorescence Resonance Energy Transfer (FRET) Studies. Specific Aim 6: Immunohistochemical Studies with the New Dyes. Specific Aim 7: Dye Stability Studies. Specific Aim 8: Protein Labeling Efficiency Studies.