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: 6589241
• 负责人: George Sachs
• 金额: $ 0.61万
• 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 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6589241
• 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.

这是一个新的申请从一个既定的调查员， 探讨H+，K+ ATP酶的结构与功能关系。此PI 建议研究一类新的抑酸药物， 咪唑并-1，2 α-吡啶，它们是酶的非共价抑制剂。的 SCH 28080和其他咪唑并吡啶的潜在结合位点将是 在转染H+，K+ ATP酶的细胞中通过动力学测量进行研究 和变异酶参与识别这一点的特定膜片段 将识别抑制剂的类别。模型将主要依赖于 最近鉴定的sr Ca ATP酶和脉孢菌H+的晶体结构 ATPases，因此，目前的建议将完善目前的模型， 提出并可用于生成结构-功能数据， H ~+，K ~+ ATP酶的离子转运作用及其受这类新的 抑酸药