SBIR Phase I: Development of Novel Dendrimer-based Technologies for Phosphorylation Analyses

这个小型企业创新研究(SBIR)第一阶段项目解决了有效分析蛋白质磷酸化的未得到满足的需求，这是一种将磷酸基团添加到蛋白质中以改变其功能的过程。蛋白质磷酸化是蛋白质的一种重要修饰，其异常与许多疾病有关。因此，在大多数生命科学研究实验室中，定性或定量地评估单个蛋白质或一类蛋白质的磷酸化状态已成为一个常规但极其重要的步骤。现有技术存在着重复性差、回收率差、成本高、选择性降低、实验时间延长等明显不足。在这个第一阶段项目中开发的平台技术将通过提供有利可图的、通用的磷酸化分析方法来极大地缓解这些缺点。这些技术将为蛋白质组学实验实现一般的磷酸化检测、经济高效的抑制剂筛选、激酶/磷酸酶活性定量和高效的磷酸肽浓缩。这项研究的更广泛/商业影响是平台技术的发展，以改进一套生化分析，并有助于发现新的治疗靶点。作为药物靶点的蛋白质磷酸化和蛋白激酶抑制剂目前正处于研发的高峰期，占药物研发总费用的30%以上。这些研发活动可以极大地受益于拟议的技术，因为它们的创新设计和多功能功能可实现最佳效率，并能够以前所未有的深度重复探索磷酸化事件。这些将提供宝贵的工具，并满足学术和工业环境中许多生物科学研究实验室/设施的需求。

This Small Business Innovation Research (SBIR) Phase I project addresses the unmet needs for effective analysis of protein phosphorylation, a process where a phosphate group is added to a protein to change its function. Protein phosphorylation is a crucial modification of proteins; its abnormalities have been implicated in many diseases. Therefore, assessing the phosphorylation status of individual proteins or classes of proteins, qualitatively or quantitatively, has become a routine but extremely important step in the majority of life science research labs. Existing technologies have glaring deficiencies, including low reproducibility, poor recovery, high cost, reduced selectivity and prolonged experiment time. The platform technology to be developed during this Phase I project will greatly alleviate these shortcomings by providing lucrative, general approaches for phosphorylation analyses. The technologies will enable general phosphorylation detection, cost-effective inhibitor screenings, kinase/phosphatase activity quantitation, and efficient phosphopeptide enrichment for proteomic experiments.The broader/commercial impacts of this research are the development of platform technology to improve a set of biochemical assays, and help the discovery of new therapeutic targets. Protein phosphorylation and kinase inhibitors as drug targets are currently at the peak of research and development (R&D), responsible for over 30% of the total drug discovery expenses. These R&D activities could greatly benefit from the proposed technologies due to their innovative design and versatile features for optimum efficiency and the ability to reproducibly explore phosphorylation events in unprecedented depth. These should provide invaluable tools and address needs of many bioscience research labs/facilities in academic and industrial settings.