Inhibitor Design and Synthesis

抑制剂设计与合成

• 批准号: 7647322
• 负责人: Maurizio Pellecchia
• 金额: $ 77.95万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7647322
• 关键词: Affect; Affinity; Anthrax disease; Anti-Bacterial Agents; Antitoxins; Antiviral Agents; Apoptosis; Bacillus anthracis; Binding; Binding Sites; Biological Assay; Bioterrorism; Cell Death; Cell Proliferation; Cells; Class; Clostridium botulinum; Collaborations; Development; Disease; Docking; Drug Design; Generations; Host Defense; Human; In Vitro; Individual; Infection; Inflammatory Response; Lead; Ligands; Location; Microbe; NMR Spectroscopy; Nuclear Magnetic Resonance; Numbers; Peptides; Pharmaceutical Chemistry; Plague; Play; Population; Poxviridae; Prevention; Principal Investigator; Process; Property; Protein Binding; Proteins; Role; Smallpox; Solutions; Synthesis Chemistry; Targeted Toxins; Techniques; Toxin; United States; Virulence; Virulence Factors; X-Ray Crystallography; Yersinia pestis; base; biothreat; design; high throughput screening; human TYRP1 protein; inhibitor/antagonist; innovation; macrophage; novel; pathogen; peptidomimetics; programs; protein expression; small molecule; small molecule libraries; virtual

This project is directed to the development of small-molecule and peptidomimetic inhibitors for blocking Bacillus anthracis (anthrax), Yersinia pestis (plague), Variola major (smallpox and other pox viruses), and Clostridium botulinum, by targeting their respective toxins: LF and PA, YopH, CrmA, BoNT/C. In close collaboration with Projects Cores, we will use a combination of virtual and high-throughput screening and novel synthetic approaches guided by NMR-based drug design strategies for generating small-molecule and peptidomimetic inhibitors. Given the arsenal of techniques proposed in this project, we anticipate being able within the course of the program to identify and characterize high affinity inhibitors for most of the targeted toxins.

该项目针对小分子和肽抑制剂的开发 通过针对其各自的毒素：LF和PA，YOPH，CRMA，BONT/c，阻止炭疽芽孢杆菌（炭疽杆菌），耶尔森氏菌（鼠疫），疫苗（鼠疫），瓦里奥拉大（天花和其他痘病毒）和肉毒杆菌。与项目核心密切合作，我们将使用 虚拟和高通量筛选以及以NMR为基础的新型合成方法 产生小分子和肽抑制剂的药物设计策略。鉴于 在该项目中提出的技术的武器库，我们预计能够在计划的过程中识别和表征大多数靶向毒素的高亲和力抑制剂。