PHOTOCLEAVABLE LINKERS AND MARKERS FOR MASS SPECTROMETRY

该项目的目标是开发新技术， 基于新型光可裂解的生物分子的检测和分析 连接体（PC-连接体）、光可裂解标记物（PC-标记物）和基质 辅助激光解吸电离质谱（MALDI-MS）。 PC- 连接体促进生物分子在表面上的捕获， 随后光释放用于通过MALDI-MS分析。PC-标记物促进 同时识别复合物中的不同生物分子 在阶段I期间，AmberGen，Inc.已经开始 开发一系列专有试剂和方法， 将PC-接头和PC-标志物掺入寡核苷酸中， proteins.开发和评价的试剂的实例包括PC-100。 氨基标记物-亚磷酰胺，用于寡核苷酸的5 '-末端标记， 固相支持合成和可掺入PC-核苷酸 酶促转化为寡核苷酸。 一种专有的方法， 具有光可裂解肽质量的寡核苷酸探针的合成 已经基于使用DNA/RNA标记物（PC-SNAP）开发了一种DNA/RNA标记物， 固相合成仪 肽质量标记物具有许多吸引人的 包括大量独特的可分辨质量的特征， 片段化稳定性和自动化合成。 在第二阶段， 这项新技术将得到进一步发展，并用于各种 应用包括PCR产物分析、快速测序 以及基于DNA和蛋白质分析的分子诊断。 拟定商业应用： 光可裂解接头和光可裂解标记物的开发 质谱法将在许多领域具有广泛的商业应用。 生物技术领域，涉及检测和分析 生物分子 产品将包括光裂解试剂， 光可裂解标记物，用于质量的光可裂解表面阵列 光谱分析和DNA和蛋白质水平的诊断分析 用于各种医疗保健应用。

The objective of this project is to develop new technology for the detection and analysis of biomolecules based on novel photocleavable linkers (PC-linkers), photocleavable-markers (PC-markers) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS). PC- linkers facilitate the capture of biomolecules on surfaces and subsequent photorelease for analysis by MALDI-MS. PC-markers facilitate simultaneous identification of different biomolecules in a complex mixture by MALDI-MS. During Phase I, AmberGen, Inc. has begun development of a range of proprietary reagents and methodologies for incorporating PC-linkers and PC-markers into oligonucleotides and proteins. Examples of reagents developed and evaluated include PC- aminotag-phosphoramidites for 5'-end labeling of oligonucleotides during solid-support synthesis and PC-nucleotides which can be incorporated enzymatically into oligonucleotides. A proprietary method for the synthesis of oligonucleotide probes with photocleavable peptide mass markers (PC-SNAPs) has been developed based on the use of a DNA/RNA solid phase synthesizer. Peptide mass markers have many attractive features which include a large set of unique resolvable masses, stability to fragmentation and automated synthesis. During Phase II, this new technology will be further developed and used in a variety of applications including the analysis of PCR products, rapid sequencing of DNA, and molecular diagnosis based on DNA and protein analysis. PROPOSED COMMERCIAL APPLICATION: The development of photocleavable linkers and photocleavable markers for mass spectrometry will have widespread commercial applications in many areas of biotechnology involving the detection and analysis of biomolecules. Products will include photocleavable reagents, photocleavable markers, photocleavable surface arrays for mass spectrometry, and diagnostic assays at both the DNA and protein level for a variety of health care applications.