Cell-Based Screen-Inhibitors of Mucin-Type O-Linked(RMI)

描述（由申请方提供）：项目总结：本提案的目标是开发用于鉴定粘蛋白型O-连接聚糖小分子抑制剂的高通量细胞检测方法。粘蛋白型O-连接聚糖结构在炎症和肿瘤转移中起关键作用;然而，尚未鉴定出小分子非碳水化合物抑制剂。本文所述的基于细胞的测定具有发现合成粘蛋白型0连接聚糖所需的任何生物合成酶的抑制剂的能力。O-连接聚糖生物合成酶的抑制剂将是探测这类碳水化合物的生物学作用的强有力的研究工具。此外，抑制剂将是开发用于治疗癌症、炎性疾病以及由流感和幽门螺杆菌引起的感染的治疗剂的起点。相关性：碳水化合物在许多人类疾病中发挥着重要作用;然而，针对这类分子的药物通常缺乏。该提案旨在通过开发高通量筛选系统来解决这一问题，以鉴定特定类别的细胞表面碳水化合物（称为粘蛋白型O-连接聚糖）的小分子抑制剂。通过本文提出的方法鉴定的小分子将具有作为研究工具的价值，并作为开发用于治疗癌症和传染病的新一类药物的起点。

DESCRIPTION (provided by applicant): Project Summary: The goal of this proposal is to develop high throughput cell-based assays for the identification of small molecule inhibitors of mucin-type O-linked glycans. Mucin-type O-linked glycan structures play critical roles in inflammation and tumor metastasis; however, no small molecule, non carbohydrate inhibitors have been identified. The cell-based assays described herein have the ability to discover inhibitors of any biosynthetic enzyme required for the synthesis of mucin-type O linked glycans. Inhibitors of O-linked glycan biosynthetic enzymes would be powerful research tools to probe the biological roles of this class of carbohydrates. Furthermore, inhibitors would be starting points to develop therapeutics for treating cancer, inflammatory diseases, and infection caused by influenza and Helicobacter pylori. Relevance: Carbohydrates play essential roles in many human diseases; however, drugs targeting this class of molecules are generally lacking. This proposal aims to solve this problem by developing a high throughput screening system to identify small molecule inhibitors of a specific class of cell surface carbohydrates known as mucin-type O-linked glycans. Small molecules identified by the methods proposed here would have value as research tools and as the starting point to develop a new class of Pharmaceuticals for treating cancer and infectious diseases.