COBRE: NDS U: SYNTHESIS: BONE, LUNG, EMPHYSEMA, ALZHEIMER, CANCER, DRUG DVMT

描述（改编自申请人摘要）：申请资金用于建立一个研究通过蛋白酶抑制靶向疾病的独特策略的中心。将采用多学科的方法，包括体外细胞相互作用、合成、药物设计、靶向递送和生物制药。该中心将协调来自化学系的四位教员（Cook, Mallik， Rodgers和Sibi）和药学系的两位教员（Balaz和Sehgal）的专业知识。该中心的科学重点将是开发基质蛋白酶的治疗性抑制剂和递送系统，包括基质金属蛋白酶（MMPs）和丝氨酸蛋白酶（SPs）家族、尿激酶纤溶酶原激活剂（uPA）和纤溶酶。大部分的努力是针对MMPs的抑制。然而，这两种丝氨酸蛋白酶在健康和疾病的基质稳态中也起着关键作用。一部分工作将用于设计和优化这些酶的抑制剂。这项工作将包括四个相互关联的项目：项目1，综合；项目2，目标/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）。COBRE中心将建立基础设施，以促进北达科他州生物医学研究的发展。从1997年7月到1999年12月，北达科他州总共向NIH提交了130份提案。在撰写本文时，NDSU有15名研究人员参与了NIH资助的项目。北达科他州大约有200名教师/研究人员从事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了该州的一个潜在增长领域。研究人员将通过建立COBRE资助的研究中心来开发这一潜力。中心将在生物医学相关领域开展新的活动，以整体方式解决上述增长领域。这些倡议包括：为北达科他州教师提供种子基金，建立研究生奖学金计划，博士后奖学金，本科生和四年制学院教师的夏季研究计划，以及NIH研讨会。本中心将保持警惕，建立和维持一个有利的环境，以促进在RO1水平上向NIH提出新的建议。

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.