Si-ROMP Hybrid Reagent/Scavengers for High Throughput Chemistry

描述（由申请人提供）：Materia, Inc.和堪萨斯大学之间的快速小企业技术转移研究旨在建立在我们目前的STTR第二期资助（R41GM076765-02）的成功基础上，该资助将于2011年3月31日到期。该提案是堪萨斯大学和加利福尼亚州帕萨迪纳市Materia公司的合作成果，旨在开发和扩大Si-ROMP混合试剂/清除剂的规模，并优化其商业化的过程。更具体地说，第一阶段将重点关注三个关键领域：(1)利用表面引发ROM聚合，从现有的和新的降冰片烯基功能化单体中生成一系列Si-ROMP试剂/清除剂，第一阶段的里程碑目标是合成六种Si-ROMP试剂。Si-OBAC、Si-ODCT、Si-OTPP、Si-OTP、Si-OACC和Si-OBP。(2)开发的Si-ROMP混合材料在流动技术中的应用，在高通量方法中实现简单和无净化的协议，第I阶段的另一个里程碑目标是展示Si-ROMP混合材料在连续流协议中的应用。第二阶段的目标是(3)Si-ROMP试剂和清除剂的工艺开发和规模扩大，包括由工业和非营利组织/合作者对Si-ROMP试剂和清除剂进行关键的beta测试；(4)利用表面引发ROM聚合，从现有和新的降龙骨烯基功能化单体中继续产生表面固定化试剂/清除剂（第一阶段的目标1）。(5)在流动技术中继续利用已开发的Si-ROMP混合材料，在高通量方法中进行易溶和无净化协议（第一阶段的目标#2）；(6)在易溶和无净化协议中利用nb标记的si颗粒来隔离nb标记的试剂/清除剂，并研究废弃Si-ROMP盒的回收利用。在我们目前资助的二期研究以及最近的出版物中，已经证明了可溶性ROMP试剂在药物发现中的应用。通过Materia， Inc.和堪萨斯大学的科学家团队，我们已经准备好迎接快速通道项目中具有挑战性的技术方面。此外，Materia的技术平台、业务开发部门和大规模生产设施将促进已开发技术从实验室向商业领域的计划过渡。Materia已经建立了一个广泛的战略联盟网络，以利用其技术和业务资源，加速下游产品的开发。首席研究员实验室、美国国立卫生研究院图书馆化学方法论中心（KU-CMLD）和Materia公司的大量资源将用于产品开发和所有商业化产品的广泛beta测试。

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.