DEVELOPMENT OF NEW ASSAYS OF MAST CELLS SECRETION

肥大细胞分泌新检测方法的开发

• 批准号: 6310457
• 负责人: RICHARD G WOODBURY
• 金额: $ 9.34万
• 依托单位: PROTEIN SYSTEMS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2001-10-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6310457
• 关键词: bioassay; cell mediated cytotoxicity; endopeptidases; histamine; histochemistry /cytochemistry; mast cell; secretion; technology /technique development

DESCRIPTION: Novel assays will be developed to provide reliable measurement of released mast cell proteases as alternatives to histamine-release assays to detect mast cell secretion. The research will evaluate synthetic substrates such as peptide 4-nitroanilides for use in calorimetric assays. Routine assays for histamine are tedious, slow, prone to error and relatively insensitive. The primary goal of the proposed research is to test the feasibility that the protease assays offer clear advantages compared to histamine-release assays. The protease assays are expected to be rapid, sensitive and adaptable to high throughput detection of mast cell secretion that will be useful to screen large numbers of compounds potentially acting on mast cells. Additionally, the assays will have utility in identifying drugs that lead to mast cell-mediated toxicity. The new assays will be used to study mast cells that produce low levels of histamine. The availability of the improved assays may stimulate mast cell research. PROPOSED COMMERCIAL APPLICATION: The ability to produce many compounds by combinatorial chemistry requires high throughput screening assays to facilitate drug discovery. New assays will permit a rapid assessment of drug candidates targeting mast cells and provide early information of potential mast cell-mediated toxicity. A screening service of this type may be of considerable commercial benefit to drug companies.

描述：将开发新的检测方法来提供可靠的测量 释放肥大细胞蛋白酶作为组胺释放测定的替代方法 检测肥大细胞的分泌。该研究将评估合成基质 例如用于量热测定的肽 4-硝基苯胺。常规检测 对于组胺来说，这些过程繁琐、缓慢、容易出错并且相对不敏感。这 拟议研究的主要目标是测试该方案的可行性 与组胺释放测定相比，蛋白酶测定具有明显的优势。 蛋白酶测定预计将是快速、灵敏且适用于高 肥大细胞分泌的通量检测将有助于筛选大量 许多可能作用于肥大细胞的化合物。此外，化验 将有助于识别导致肥大细胞介导的药物 毒性。新的检测方法将用于研究产生低浓度的肥大细胞 组胺水平。改进检测的可用性可能会刺激肥大 细胞研究。 拟议的商业应用： 通过组合化学生产多种化合物的能力需要很高的 通量筛选分析以促进药物发现。 新的检测方法将允许 快速评估针对肥大细胞的候选药物并提供早期 潜在的肥大细胞介导的毒性信息。 此类筛查服务 可能会给制药公司带来可观的商业利益。