Anti-Inflammatory Bioconjugates

抗炎生物结合物

• 批准号: 6995211
• 负责人: BENJAMIN P BOWEN
• 金额: $ 10.5万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6995211
• 关键词: antiinflammatory agents; biotechnology; biotherapeutic agent; cell adhesion; cell adhesion molecules; cell cell interaction; cell migration; chemical conjugate; dextrans; disease /disorder model; dosage; drug design /synthesis /production; immunologic substance development /preparation; immunopharmacology; intravital microscopy; laboratory rat; leukocytes; mesentery; peptides; receptor binding; selectins; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium

DESCRIPTION (provided by applicant): The research objective of this work is to develop a dextran-peptide conjugate that selectively binds injured tissue surfaces to form a protective colloid barrier against trauma-induced inflammatory cell damage to healthy tissues. This therapy could have a tremendous impact on the morbidity and mortality rates of many pathological processes. Aim 1: To synthesize and characterize several anti-inflammatory bioconjugate formulations. Aim 2: To perform in vitro assays to verify biochemical and biological function of the dextran-peptide conjugates. Aim 3: To determine the influence of the bioconjugate on leukocyte-endothelium interactions in vivo using rat mesenteric venules stimulated by TNF-a. The training involved in this appointment will equip the applicant with the skills necessary to perform state-of-the-art research in molecular therapeutics. This field is a new direction from the applicant's chemical engineering and biophysical chemistry training, and will work synergistically in the long run with the previous training. When the appointment is completed, the applicant will be well-qualified to perform research integrating molecular therapeutics and ultrasensitive analysis as an independent researcher. Over the four-year duration of this award, areas of work will include didactic coursework, training "at the bench" at Arizona State University in Tempe, Arizona and intravital microscopy training with Dr. Stuart Williams at The University of Arizona in Tucson, Arizona. For the entire duration of this project 100% of the applicant's time will be spent working on the proposed work and training activities. A projected timeline of the tasks that will be performed each year is listed below. Year 1: didactic coursework, synthesis of the bioconjugates, binding affinity measurements of the bioconjugates, training in the responsible conduct of research; Year 2: didactic coursework, in vitro testing of bioconjugates, manuscript preparation; Year 3: training in animal surgery, intravital microscopy training, preliminary in vivo testing of the optimal bioconjugate, manuscript preparation; and Year 4: in vivo testing of the optimal bioconjugate and manuscript preparation.

描述（由申请人提供）： 这项工作的研究目标是开发一种葡萄糖肽结合物，该葡萄糖结合物有选择地结合受伤的组织表面，形成保护性胶体屏障，以防止创伤引起的炎症细胞对健康组织的炎症损害。这种疗法可能会对许多病理过程的发病率和死亡率产生巨大影响。目标1：合成和表征几种抗炎生物缀合物制剂。目标2：进行体外测定，以验证葡萄糖肽缀合物的生化和生物学功能。目标3：使用TNF-A刺激的大鼠肠系膜静脉，确定生物缀合物对体内白细胞 - 内皮相互作用的影响。涉及此任命的培训将使申请人能够为进行分子疗法进行最先进的研究所需的技能。该领域是申请人的化学工程和生物物理化学培训的新方向，从长远来看，随着先前的培训，将协同工作。任命完成后，申请人将获得良好的资格进行研究，以整合分子治疗剂和作为独立研究人员的超敏分析。在该奖项的四年期间，工作领域将包括教学课程，亚利桑那州亚利桑那州立大学在亚利桑那州亚利桑那州立大学的“替补席”培训，以及在亚利桑那州图森的亚利桑那大学的Stuart Williams博士与Stuart Williams博士一起培训。在整个该项目的整个期限里，申请人的时间的100％将花在拟议的工作和培训活动上。下面列出了每年将执行的任务的预计时间表。第1年：教学课程，生物缀合物的合成，生物轭物的结合亲和力测量，负责任的研究培训；第二年：教学课程，生物缀合物的体外测试，手稿准备；第三年：动物外科训练，插入显微镜训练，最佳生物缀合物的体内初步测试，手稿准备；和第4年：最佳生物缀合物和手稿制备的体内测试。