Preparation of New Long Wavelength Fluorescent Dyes

新型长波长荧光染料的制备

• 批准号: 6735260
• 负责人: Nicholas Cairns
• 金额: $ 63.41万
• 依托单位: COMBINIX, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735260
• 关键词: chemical stability; chemical structure function; chemical synthesis; combinatorial chemistry; cyanine; fluorescence polarization; fluorescence resonance energy transfer; fluorescent dye /probe; high performance liquid chromatography; immunocytochemistry; infrared radiation; ionophores

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.

描述（由申请人提供）：在电磁波谱的长可见光/近红外（NIR）区域工作的新型荧光染料已被证明可以作为此类靶向分子探针和示踪剂的优异报告组分。目前此类染料的供应非常短缺，并且市售的染料非常昂贵或者仅在严格限制性的许可协议下才能获得。许多可用的染料具有不良特性，例如相对较高的非特异性结合和聚集倾向，并且部分由于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型组合化学技术发现新型长波长近红外扩展方酸菁染料，这些技术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。将开发新的固相合成途径，以实现克级高纯度染料的合成，并将产生更广泛地供研究和科学界使用的产品。 具体目标有 8 个： 具体目标 1：利用第一阶段开发的合成方法进一步合成 240 种新型长波长/近红外扩展方酸菁染料。 具体目标 2：新型染料的小规模纯化和表征。具体目标 3：扩大目标 1 和 2 中选定的 20 种花青染料的合成规模。目标 4：荧光偏振 (FP) 研究。具体目标 5：评估新型染料在荧光共振能量转移 (FRET) 研究中的性能。具体目标 6：使用新染料进行免疫组织化学研究。具体目标 7：染料稳定性研究。具体目标 8：蛋白质标记效率研究。