COBRE: NDS U: BIOPHARMACOLOGY: MS, PROTEASE

描述(摘自申请者的摘要)：要求提供资金，以建立一个研究通过抑制蛋白水解酶来针对疾病的独特策略的中心。将采取一种涉及体外细胞相互作用、合成、药物设计、靶向递送和生物制药的多学科方法。该中心将协调来自化学的四名教员(库克、马利克、罗杰斯和西比)和药房的两名教员(巴拉兹和塞加尔)的专业知识。该中心的科学重点将是开发治疗基质蛋白酶的抑制剂和递送系统，包括基质金属蛋白酶(MMPs)家族和丝氨酸蛋白酶(SPS)、尿激酶型纤溶酶原激活剂(UPA)和纤溶酶。大部分的努力是针对MMPs的抑制。然而，在健康和疾病中，这两种丝氨酸蛋白酶也在基质动态平衡中发挥关键作用。部分工作将针对这些酶的抑制剂的设计和优化。这项工作将由四个相互关联的项目组成：项目1，合成；项目2，靶向/交付；项目3，生物制药/药物设计；项目4，体外细胞相互作用(核心)。科布雷中心将建设基础设施，以促进北达科他州生物医学研究的增长。从1997年7月至1999年12月，从北达科他州到国立卫生研究院共提交了130份建议书。截至撰写本文时，南加州州立大学有15名研究人员参与了美国国立卫生研究院资助的项目。在北达科他州，大约有200名教职员工/研究人员拥有与生物医学相关的研究项目。研究人员数量和拨款申请活动之间的差距代表着该州一个潜在的增长领域。研究人员将通过建立科布雷资助的研究中心来开发这一潜力。该中心将在生物医学相关领域发起新的活动，以全面解决上述增长领域。这些举措包括：为北达科他州教师提供种子基金，设立研究生奖学金计划，博士后奖学金，为四年制大学本科生和教职员工提供暑期研究计划，以及NIH研讨会。该中心将警惕地建设和维护一个良好的环境，以促进在RO1级向NIH提交新提案。

DESCRIPTION (Adapted from the applicant's abstract): Funds are requested to establish a Center for the investigation of unique strategies to target disease through protease inhibition. A multi-disciplinary approach involving in vitro cellular interactions, synthesis, drug design, targeting-delivery, and biopharmaceutics will be undertaken. The Center will coordinate the expertise of four faculty from Chemistry (Cook, Mallik, Rodgers, and Sibi) and two from Pharmacy (Balaz and Sehgal). The scientific focus of the Center will be the development of therapeutic inhibitors and delivery systems for matrix proteinases, including the family of matrix metalloproteinases (MMPs) and the serine proteases (SPs), urokinase plasminogen activator (uPA) and plasmin. The majority of effort is directed toward the inhibition of MMPs. However, the two serine proteases also play critical roles in matrix homeostasis in both health and disease. A portion of the effort will be directed towards the design and optimization of inhibitors for these enzymes. The effort will consist of four interrelated projects: Project 1, Synthesis; Project 2, Targeting/Delivery; Project 3, Biopharmaceutics/Drug Design; Project 4, in vitro Cellular Interactions (Core). The COBRE Center will build the infrastructure to foster growth of biomedical research in North Dakota. From July 1997 to December 1999 a total of 130 proposals from North Dakota to NIH have been submitted. As of this writing, NDSU has 15 researchers with NIH funded programs. There are on the order of 200 faculty/researchers with biomedically relevant research programs in North Dakota. The disparity between the number of researchers and grant proposal activity represents a potential growth area for the state. The investigators will develop this potential through establishment of the COBRE funded Research Center. The Center will initiate new activities in biomedically relevant areas to address the aforementioned growth areas in a holistic way. These initiatives include: seed grants for North Dakota faculty, establishment of a graduate fellowship program, post-doctoral fellowships, summer research program for undergraduates and faculty from four-year colleges, and NIH workshops. The Center will be vigilant in building and maintaining a favorable environment for fostering new proposals to the NIH at the RO1 level.