PEPTIDE COMBINATORIAL LIBRARY--IDENTIFY TUMOR ANTIGEN & CREATE THERAPY VACCINES

该计划的中心目标是继续开发一种 广泛收集小分子组合文库，并使用 这些文库在基于细胞的筛选试验中用于设计新的 癌症治疗学。四名知名高级调查员，每人 指导他们自己的项目，有三个核心参与其中 合作努力。一个项目直接参与了进一步的 新的合成小型组合文库的多样性发展。 第二个项目建议筛选大量的多肽 触发细胞毒性T细胞的分子组合文库 可能是有效的疫苗，针对选定的癌症。第三个项目 将筛选其他小分子、杂环、多肽类和有机类 可能控制异常细胞周期的其他化合物的文库 事件，类似地，第四个项目将探索库以 确定影响细胞凋亡途径各个步骤的化合物。 免疫抑制，异常细胞周期检查点，以及 正常的程序性细胞死亡机制经常涉及到 肿瘤的发病机制。除了行政核心，该计划 也包括专门为生产而设计的专用核心， 分发和跟踪当前存在的合成库，以及 另外一组多样化的组合生物学文库，它们具有 最近提供的信息和单独的化合物 这些研究的结果将为我们提供对 基于小分子的疫苗设计和药物中的一般问题 细胞分裂异常和事件改变的调控设计 是典型的恶性细胞的凋亡途径。

The central goal of this program is to continue the development of an extensive collection of small molecule combinatorial libraries, and to use these libraries in cell-based screening assays for the design of new therapeutics for cancer. Four well-established senior investigators, each directing their own project, and three cores are involved in this collaborative effort. One project is directly involved in the further development of diversity in new synthetic small combinatorial libraries. A second project proposes to screen an extensive collection of peptide combinatorial libraries for molecules that trigger cytotoxic T cells and may be effective as vaccines against selected cancers. The third project will screen other small molecule, heterocycle, peptidomemetic and organic libraries for other compounds that might control abnormal cell cycle events, and similarly, the fourth project will explore libraries to identify compounds that affect various steps in the apoptosis pathway. Immune suppression, abnormal cell cycle check points, and dysregulation of normal programmed cell death mechanisms are frequently involved in the pathogenesis of tumors. Aside from an administrative core, the program also includes to specialized cores specifically designed to produce, distribute and track synthetic libraries that currently exist, as well as an additional set of diverse combinatorial biology libraries that have recently been made available Information and individual compounds resulting from these studies will provide important insights into the general problem of vaccine design based on small molecules, and in drug design for the regulation of abnormal cell division and altered events in the apoptosis pathway that are characteristic malignant cells.