Microwave-Accelerated Microchip Combinatorial Chemistry

描述(申请人提供)：蛋白质组学和基因组学的爆炸性增长产生了对研究小分子与蛋白质或核酸之间结合作用的快速和方便的手段的需求。我们计划使用一种名为微波加速靶向触发反应(MattR)的新平台技术来极大地加速和无缝集成基于芯片的组合多肽库的合成和生物分析。MattR芯片包含微波活性介电材料，当受到微波照射时，这些材料的温度会急剧上升。MattR包括两个“子技术”--微波加速合成(MAS，制备)和微波诱导化学发光(MIC，分析)。在MAS中，局部加热缩短了固相有机合成时间。在MIC中，通过使用微波触发的化学发光检测与抗体、酶或受体的相互作用来筛选合成的文库。如果成功，MAS/MIC有望成为小分子药物发现和化学基因组学/蛋白质组学基础研究的有价值的研究工具。我们的具体目的是通过在一个芯片上合成和筛选两个10个氨基酸的多肽来证明MAS/MIC的可行性。第一个目标是显示在合成来自c-myc的多肽和相同长度的对照多肽方面，与文献方法相比，速度至少提高了四倍。我们的第二个目标是利用化学发光标记的抗c-myc抗体，利用MIC技术快速检测c-myc多肽。Mirari计划将“微波发光计”仪器、芯片和试剂盒商业化，用于组合合成和随后对聚焦的多肽库进行生物分析。我们相信，这些产品将大大加快药物发现的速度，并使更好的药物能够在更短的时间内开发出来。

DESCRIPTION (provided by applicant): The explosive growth of proteomics and genomics has created a demand for rapid and convenient means of studying binding interactions between small molecules and proteins or nucleic acids. We plan to use a new platform technology called Microwave-Accelerated Targeted Triggered Reactions (MATTR) to dramatically accelerate and seamlessly integrate chip-based synthesis and bioanalysis of combinatorial peptide libraries. MATTR chips contain microwave-active dielectric materials that when irradiated by microwaves undergo sharp temperature increases. MATTR consists of two "sub-technologies" - Microwave-Accelerated Synthesis (MAS, preparative) and Microwave-Induced Chemiluminescence (MIC, analytical). In MAS, the localized heating shortens solid phase organic synthesis times. In MIC, synthesized libraries are screened by detecting interactions with antibodies, enzymes, or receptors using microwave-triggered chemiluminescence. If successful, MAS/MIC promises to be a valuable research tool in small molecule drug discovery and in basic research in chemical genomics/proteomics. Our specific aims are to demonstrate the feasibility of MAS/MIC by using the technology to synthesize and screen two 10-amino acid peptides on a chip. The first aim is to show at least a four-fold increase in speed compared to a literature method in synthesizing a peptide derived from c-myc as well as a control peptide of the same length. Our second aim is to use a chemiluminescently-labeled anti-c-myc antibody to rapidly detect the c-myc peptide using MIC technology. Mirari plans to commercialize "microwave luminometer" instruments, chips, and reagent kits for combined synthesis and subsequent bioanalysis of focused peptide libraries. We believe these products will sharply accelerate drug discovery and enable better drugs to be developed in shorter times.