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Microwave-Accelerated Microchip Combinatorial Chemistry

微波加速微芯片组合化学

基本信息

批准号：
6833904
负责人：
MARK T. MARTIN
金额：
$ 9.9万
依托单位：
MIRARI BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-15 至 2005-03-14
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：蛋白质组学和基因组学的爆炸性增长已经产生了对研究小分子与蛋白质或核酸之间的结合相互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）的新平台技术来显着加速和无缝集成组合肽库的基于芯片的合成和生物分析。MATTR芯片含有微波活性介电材料，当被微波照射时，温度急剧上升。MATTR由两个“子技术”组成-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。如果成功的话，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一个有价值的研究工具。我们的具体目标是通过使用该技术在芯片上合成和筛选两个10-氨基酸肽来证明MAS/MIC的可行性。第一个目的是与文献方法相比，在合成衍生自c-myc的肽以及相同长度的对照肽中显示出至少四倍的速度增加。我们的第二个目标是使用荧光标记的抗c-myc抗体，使用MIC技术快速检测c-myc肽。Mirari计划将“微波光度计”仪器、芯片和试剂盒商业化，用于集中肽库的组合合成和随后的生物分析。我们相信这些产品将大大加快药物发现，并使更好的药物在更短的时间内开发出来。