NOVEL CYCLIC-PEPTIDE-BASED ANTIMITOTICS

新型环肽抗有丝分裂剂

• 批准号: 2862902
• 负责人: Robert SCOTT LOKEY
• 金额: $ 3.17万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2862902
• 关键词: antimitotics; chemical structure function; cyclic peptides; cyclins; cytotoxicity; membrane permeability; peptide chemical synthesis; peptide library

We will synthesize a small library of heptapeptide scaffolds to explore the effects of scaffold conformation on cyclization and cell permeability. We will select several novel cell-permeable cyclic scaffolds for elaboration into libraries of potential protein ligands and screen them for effects on the cell cycle in a number of different assays. Several active compounds will be chosen for further study. We are particularly interested in compounds that arrest cells in mitosis by directly perturbing the degradation of cyclin B or by targeting components of the mitotic spindle and thus triggering the mitotic checkpoint pathway.

我们将合成一个小的七肽支架文库，以探索支架构象对环化和细胞通透性的影响。我们将选择几种新的细胞渗透性的循环支架来精加工到潜在的蛋白质配体的库中，并在一些不同的分析中筛选它们对细胞周期的影响。将选择几个活性化合物进行进一步的研究。我们特别感兴趣的是那些通过直接干扰细胞周期蛋白B的降解或通过靶向有丝分裂纺锤体的组件从而触发有丝分裂检查点途径来阻止细胞有丝分裂的化合物。