CORE--SYNTHETIC /MEDICINAL CHEMISTRY

合成/药物化学核心（SynCore）将为这种新型小分子治疗CF项目提供至关重要的技术支持。该项目的总体目标是发现新的CF相关小分子，这些小分子可以作为突变CFTR的增强剂，纠正deltaF508-CFTR细胞错误加工，CFTR抑制剂，非病毒基因传递增强剂，CF患者培养细胞中鼻腔pd和氯化物运输之间的相关性资源，抗菌剂，基于水通道蛋白的腺体液体分泌增强剂，CFTR激活剂增强肺泡液清除，腺体粘蛋白分泌抑制剂，资源慢性抑制猪CFTR功能，试剂可用于定义ASL在CF的先天免疫防御中的作用，试剂可用于定义缺陷的作用

The Synthesis/Medicinal Chemistry Core (SynCore) will provide enabling technology vital to this NOVEL SMALL-MOLECULE THERAPIES FOR CF program project. The overall goal of this program is the discovery of novel CF-relevant small-molecules which serve as potentiators of mutant CFTRs, correctors deltaF508-CFTR cellular misprocessing, CFTR inhibitors, enhancers of non-viral gene delivery, resources for correlation between nasal PDs and chloride transport cultured cells from CF subjects, antimicrobials, aquaporin-based enhancers of gland fluid secretion, CFTR activators to enhance alveolar fluid clearance, inhibitors of glandular mucin secretion, resources to chronically inhibit CFTR function in pigs, reagents useful in defining the role of ASL in innate immune defense in CF, reagents useful in defining the role of defective airway submucosal gland secretion in CF lung disease, and hit-to-lead discovery libraries for high-throughput screening. SynCore will figure prominently in this program's efforts to realize these objectives by preparing lead discovery libraries designed to explore hits provide by high-throughput screening and providing study-relevant quantities of the lead compounds required for the studies outlined in the PROJECTs2. The SynCore specific aims are to (1) prepare chemically pure, structurally characterized small-molecule HIT and LEAD compounds for application by the PROJECTS and the COREs and (2) prepare hit-to-lead discovery libraries designed to structurally explore hits identified by high-throughput screening.