Preparation of New Long Wavelength Fluorescent Dyes

描述（由申请人提供）：在电磁波谱的长可见/近红外（NIR）区域工作的新型荧光染料已被证明是这种靶向分子探针和示踪剂的优秀报告成分。目前，这种染料的供应非常短缺，而那些商业上可用的染料要么非常昂贵，要么只有在严格限制的许可协议下才能获得。许多可用的染料具有不希望的特性，例如相对较高的非特异性结合和聚集倾向，并且由于部分未优化的合成方法而价格昂贵。该应用的主要重点是通过新的组合化学技术发现新的长波长近红外扩展方碱染料，这些染料设计用于高通量筛选，荧光偏振，生物医学成像和其他适用技术，如免疫荧光显微镜和荧光激活细胞分选和计数。新的固相合成途径将被开发出来，这将允许以克级合成高纯度的染料，并将产生更广泛地用于研究和科学界的产品。

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.