DEVELOPMENT OF NEW ASSAYS OF MAST CELLS SECRETION

描述：将开发新的检测方法，以提供可靠的测量， 释放的肥大细胞蛋白酶作为组胺释放测定的替代物， 检测肥大细胞分泌。该研究将评估合成基质 例如用于量热分析的肽4-硝基苯胺。常规测定 对于组胺来说是乏味的，缓慢的，容易出错的，相对不敏感的。的 拟议研究的主要目标是测试 与组胺释放测定相比，蛋白酶测定提供了明显的优点。 蛋白酶测定法具有快速、灵敏、适用性强等优点， 肥大细胞分泌的通量检测，这将有助于筛选大 可能作用于肥大细胞的化合物的数量。此外，测定 将在鉴定导致肥大细胞介导的 毒性新的检测方法将用于研究肥大细胞， 组胺水平。改进的检测方法的可用性可能会刺激肥大细胞 细胞研究 拟定商业应用： 通过组合化学生产许多化合物的能力需要很高的 通量筛选测定以促进药物发现。 新的检测方法将允许 快速评估靶向肥大细胞的候选药物， 潜在肥大细胞介导毒性的信息。 这种类型的放映服务 可能对制药公司有相当大的商业利益。

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.