Si-ROMP Hybrid Reagent/Scavengers for High Throughput Chemistry

描述(由申请者提供)：这项在MATRIA，Inc.和堪萨斯大学之间进行的快速通道小型企业技术转让研究旨在建立在我们目前STTR第二阶段资助(R41GM076765-02)成功的基础上，该资助将于2011年3月31日到期。这项提议是堪萨斯大学和加利福尼亚州帕萨迪纳市的MATRIA，Inc.之间的合作努力，旨在开发和扩大Si-ROMP杂化试剂/清道夫，并优化其商业化过程。更具体地说，第一阶段将集中在三个关键领域：(1)从现有的和新的降冰片基功能化单体利用表面引发的在二氧化硅表面上的ROM聚合生成一系列硅-ROMP试剂/清除剂，第一阶段的里程碑目标是合成六种硅-ROMP试剂：Si-OBAC、Si-ODCT、Si-OTPP、Si-OTP、Si-OACC和Si-OBP，(2)将开发的Si-ROMP杂化材料用于流动技术中，用于高通量方法中的简便和免净化方案，另一个第一阶段的里程碑目标是展示硅-ROMP杂化材料在连续流动协议中的应用。第二阶段的目标是(3)硅-ROMP试剂和清除剂的工艺开发和扩大，包括工业和非营利性组织/合作者对硅-ROMP试剂和清除剂的关键贝塔测试，(4)利用表面引发的只读存储器聚合(阶段1中的目标#1)从现有的和新的降冰片基功能化单体中继续产生表面固定化试剂/清除剂，(5)继续在流动技术中利用开发的硅-ROMP杂化材料，用于高通量方法中的简便和免净化协议(阶段1中的目标#2)，以及(6)利用Nb标记的硅颗粒以简便、免净化的方法隔离Nb标记的试剂/清除剂，并对废Si-ROMP墨盒的回收进行了研究。通过我们目前资助的第二阶段的一些研究以及最近的出版物，已经证明了可溶版本的ROMP试剂在药物发现中的应用。我们已经做好了充分的准备，通过MATRIA公司和堪萨斯大学的科学家合作，满足拟议的快速通道计划的挑战性技术方面。此外，Matia的技术平台、业务开发部门和大型制造设施将促进已开发技术从实验室到商业领域的计划过渡。Matia已经建立了广泛的战略联盟网络，以利用其技术和业务资源，并加快下游产品的开发。首席研究员实验室、堪萨斯大学NIH图书馆开发化学方法学中心(KU-CMLD)和MATRIA公司的大量资源将用于产品开发和对所有商业化产品进行广泛的Beta测试。 公共卫生相关性：该项目名为高通量化学的硅-ROMP杂化试剂/清除剂，旨在生产高通量化学中使用的高负载、硅-ROMP衍生的杂化试剂/清除剂并将其商业化。

DESCRIPTION (provided by applicant): This Fast Track Small Business Technology Transfer study between Materia, Inc. and the University of Kansas intends to build upon successes of our current STTR Phase II grant (R41GM076765-02) which expires on March 31, 2011. This proposal is a collaborative effort between the University of Kansas and Materia, Inc. in Pasadena, CA that aims to develop and scale-up Si-ROMP hybrid reagents/scavengers and optimize the process for their commercialization. More specifically, Phase I will focus on three key areas: (1) Generation of an array of Si-ROMP reagent/scavengers from existing and new norbornenyl-functionalized monomers utilizing surface-initiated ROM polymerization off SiO2 surfaces, with a Phase I milestone goal to synthesize six Si- ROMP reagents: Si-OBAC, Si-ODCT, Si-OTPP, Si-OTP, Si-OACC and Si-OBP, (2) Utilization of the developed Si-ROMP hybrid materials in flow-through technology for facile and purification-free protocols in high throughput methods, with another Phase I milestone goal demonstrating utilization of Si-ROMP hybrid materials in continuous-flow protocols. The Phase II goals are (3) process development and scale-up of Si-ROMP reagents and scavengers including key beta-testing of Si-ROMP reagents and scavengers by industrial and non-profit organization/collaborators, (4) continued generation of surface-immobilized reagent/scavengers from existing and new norbornenyl-functionalized monomers utilizing surface-initiated ROM polymerization (Aim #1 in Phase 1), (5) continued utilization of the developed Si-ROMP hybrid materials in flow-through technology for facile and purification-free protocols in high throughput methods (Aim #2 in Phase 1), and (6) utilization of Nb-tagged Si-particles to sequester Nb-tagged reagents/scavengers in facile and purification-free protocols and investigation into recycling of spent Si-ROMP cartridges. Application of soluble versions of ROMP reagents for drug-discovery has been demonstrated through a number of studies in our currently funded Phase II as well as in recent publications. We are well positioned to meet the challenging technical aspects of the proposed Fast Track program through teaming of scientists at Materia, Inc. and the University of Kansas. Moreover, Materia's technology platforms, its business development unit, and large scale manufacturing facilities will facilitate the planned transition of the developed technologies out of the laboratory and into the commercial realm. Materia has developed an extensive strategic alliance network to leverage its technical and business resources and accelerate downstream product development. Extensive resources in the Principal Investigator's laboratory, the NIH Center in Chemical Methodologies for Library Development at the University of Kansas (KU-CMLD), and at Materia, Inc. will be utilized toward product development and extensive beta testing of all products offered for commercialization. PUBLIC HEALTH RELEVANCE: This project entitled Si-ROMP Hybrid Reagent/Scavengers for High Throughput Chemistry aims for the production and commercialization of high-load, Si-ROMP-derived hybrid reagents/scavengers for use in high throughput chemistry.