THE GASTRIC ACID PUMP AS A TARGET FOR ULCER TREATMENT

胃酸泵作为溃疡治疗的目标

• 批准号: 6524310
• 负责人: George Sachs
• 金额: $ 24.95万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524310
• 关键词: antiulcer drug; benzimidazole analog; binding sites; chemical models; enzyme inhibitors; enzyme mechanism; enzyme structure; gastric acid; hydrogen potassium exchanging ATPase; hydrogen transport; molecular dynamics; pharmacokinetics

This is a new application from an established investigator to investigate structure function relationships of the H+,K+ ATPase. This PI proposes to investigate a new class of acid suppressant medication, imidazo-1,2alpha-pyridnes, which are non-covalent inhibitors of the enzyme. The potential binding sites of SCH28080 and other imidazo-pyridines will be investigated by kinetic measurements in cells transfected with the H+,K+ ATPase and mutated enzyme. Specific membrane segments involved in recognition of this class of inhibitors will be identified. Models will largely rely on the recently identified crystal structure of sr Ca ATPase and Neurospora H+ ATPases, thus the current proposal will refine the model that currently is proposed and maybe used to generate structure-function data for understanding the ion transport role of H+,K+ ATPase and its regulation by this new class of acid suppressant drugs.

这是一位资深研究者提出的新申请 研究 H+、K+ ATP 酶的结构功能关系。这个PI 提议研究一种新型抑酸药物， 咪唑并-1,2α-吡啶，是该酶的非共价抑制剂。这 SCH28080 和其他咪唑并吡啶的潜在结合位点将是 通过 H+、K+ ATP 酶转染细胞的动力学测量进行研究 和突变酶。参与识别这一点的特定膜片段 将确定抑制剂的类别。模型将很大程度上依赖于 最近鉴定出 sr Ca ATPase 和脉孢菌 H+ 的晶体结构 ATPases，因此当前的提案将完善当前的模型 提出并可能用于生成结构功能数据以供理解 H+、K+ ATP 酶的离子转运作用及其对此类新型酶的调节 抑酸药。