DEVELOPMENT OF NEW ASSAYS OF MAST CELLS SECRETION

描述：将开发新的分析方法，以提供可靠的测量 释放的肥大细胞蛋白水解酶替代组胺释放试验 检测肥大细胞分泌情况。这项研究将评估合成底物 例如量热法分析中使用的多肽4-硝基苯胺。常规化验 因为组胺是繁琐的、缓慢的、容易出错的，而且相对不敏感。这个 拟议研究的主要目标是测试 与组胺释放分析相比，蛋白水解酶分析具有明显的优势。 该方法具有快速、灵敏、高适应性等特点。 肥大细胞分泌物的吞吐量检测将有助于筛查 可能作用于肥大细胞的化合物数量。此外，化验结果显示 将在识别导致肥大细胞介导的药物方面具有实用价值 毒性。新的检测方法将被用于研究产生Low的肥大细胞。 组胺水平。改进的化验方法的可用性可能会刺激MAST 细胞研究。 建议的商业应用： 通过组合化学产生许多化合物的能力要求很高 吞吐量筛选分析，以促进药物发现。新的化验方法将允许 针对肥大细胞的候选药物的快速评估并提供早期 潜在的肥大细胞介导的毒性信息。这类放映服务 可能会给制药公司带来相当大的商业利益。

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.