COMBINATORIAL CYCLODEPSIPEPTIDE LIBRARIES FROM DIDEMNINS

来自 Didemnins 的组合环缩肽文库

• 批准号: 2011290
• 负责人: PAUL G GROTHAUS
• 金额: $ 10万
• 依托单位: HAWAII BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2011290
• 关键词: cyclic peptides; method development; peptide chemical synthesis; peptide library; peptide structure; protein structure function

The overall goal of this project is to optimize the inherent cytotoxicity, antiviral, and immunomodulatory activity of the didemnins and eventually develop new drugs for the treatment of cancer, viral infections, and immune disorders. In Phase I, a new solid-phase synthesis of didemnin A and a new method for the cyclization-cleavage of this compound from the solid support will be developed. This methodology will then be used to synthesize a small cyclodepsipeptide library. Eventually, these combinatorial chemistry techniques will be utilized to generate large diverse libraries of cyclodepsipeptides which will be screened for useful bioactivity. beads which are identified in these screens will be used to design subsequent focused libraries, so as to further optimize useful bioactivity. Suitable candidates would undergo further testing and development in collaboration with a pharmaceutical partner. PROPOSED COMMERCIAL APPLICATION: New therapies to treat cancer, viral infections, and immune disorders are urgently needed. Didemnins represent valuable leads in each of these disease categories. The proposed technology would greatly facilitate the search for active compounds structurally related to the didemnins. In addition, the methods being developed should be applicable to other cyclic peptides and depsipeptides of varying ring size and sequence for the identification of drugs for other diseases.

该项目的总体目标是优化固有的 Dodemnins的细胞毒性，抗病毒和免疫调节活性 并最终开发用于治疗癌症，病毒的新药 感染和免疫疾病。 在第一阶段，新的固相 DodemnI A的合成和一种新方法用于环化裂解 将开发从稳固支撑的化合物。 这种方法 然后将用于合成一个小的环肽肽库。 最终，这些组合化学技术将用于 产生大量的环肽二肽库，这将是 筛选有有用的生物活性。 这些珠子在这些珠子中识别 屏幕将用于设计随后的集中库，以便 进一步优化有用的生物活性。 合适的候选人会经历 与药品合作进行进一步测试和开发 伙伴。 拟议的商业应用：治疗癌症，病毒的新疗法 迫切需要感染和免疫疾病。 Didemnins代表 这些疾病类别中的每一个都有宝贵的潜在客户。提议 技术将极大地促进寻找活跃化合物 与didemnins结构上有关。另外，方法为 开发的应适用于其他环状肽和Depspeptides 鉴定药物的环大小和序列 其他疾病。