DRUG DISCOVERY BY MIRROR IMAGE LIGAND DISPLAY

通过镜像配体显示发现药物

• 批准号: 6174000
• 负责人: ANTHONY CARLYLE FORSTER
• 金额: $ 13.93万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-22 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6174000
• 关键词: HIV envelope protein gp41; drug discovery /isolation; interleukin 8; intermolecular interaction; oncoproteins; peptide analog; receptor binding; stereoisomer

I am a physician-scientist with a Ph.D. in nucleic acid biochemistry who is within a year of completing an anatomical pathology residency at the Brigham and Women's Hospital. My immediate goal is to resume research, after a three-year absence from the laboratory, to learn the fields of protein biochemistry and stucture in the laboratory of Dr. Blacklow at the Brigham and Women's Hospital, Department of Pathology. This will give me the training necessary to pursue my long term goal of translational research in protein pharmacology. The overall goal of these studies is to test the feasibility of developing D-peptide drug candidates using the method of mirror image phage display (Schumacher et al., 1996; Forster, 1996; Fig. 1). The specific aims of this proposal are: 1. To establish that the D-enantiomer of a selected L-peptide ligand of D-interleukin-8 binds specifically and with measurable affinity to L-interleukin-8. 2. To investigate the specific molecular interactions responsible for the measured affinity and specificity of the D-peptide for the interleukin-8 target. 3. To apply this strategy for drug discovery to other potential therapeutic targets, including the gp41 subunit of the HIV envelope glycoprotein and the breast-cancer specific, cell- surface glycoprotein MUC1.

我是一个拥有博士学位的物理学家兼科学家。他在布里格姆妇女医院完成了一年的解剖病理学实习。 我的近期目标是在离开实验室三年后，重新开始研究，在布莱根妇女医院病理科的布莱克洛博士的实验室学习蛋白质生物化学和结构领域。 这将给我必要的培训，以追求我在蛋白质药理学转化研究的长期目标。这些研究的总体目标是测试使用镜像噬菌体展示方法开发D-肽药物候选物的可行性（Schumacher等人，1996; Forster，1996; Fig. 1）. 该提案的具体目标是：1.确定D-白细胞介素-8的选定L-肽配体的D-对映异构体与L-白细胞介素-8特异性结合且具有可测量的亲和力。2.研究导致D-肽对白细胞介素-8靶点测定亲和力和特异性的特异性分子相互作用。3.将这种药物发现策略应用于其他潜在的治疗靶点，包括HIV包膜糖蛋白的gp 41亚基和乳腺癌特异性细胞表面糖蛋白MUC 1。