Peptide Morphing: Rational Design of Separase Inhibitors

肽变形：分离酶抑制剂的合理设计

• 批准号: 6747260
• 负责人: Webster L Santos
• 金额: $ 4.3万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6747260
• 关键词: HeLa cells; active sites; biotechnology; cell morphology; computer simulation; cysteine endopeptidases; enzyme inhibitors; enzyme substrate; fluorescence microscopy; ligands; molecular dynamics; open reading frames; peptide chemical synthesis; postdoctoral investigator; protein engineering; structural biology

DESCRIPTION (provided by applicant): Separase has recently been identified as a cysteine protease that cleaves the Scc1 subunit of cohesin, a complex protein that physically connects sister chromatids and serves important functions in mitotic spindle dynamics. This proposal applies the recently described technique of peptide morphing in the rational design and synthesis of small nonpeptidic molecules to bind and inhibit separase. It is our hope that this proposal will demonstrate the power of peptide morphing by presenting a functionally rich and stereo diversified ligand structure to a protein target of urgent biologic interest and significance. Inhibition of separase, particularly at the active site, should shed light on key aspects of chromosome biology.

描述（由申请人提供）：分离酶最近被鉴定为一种半胱氨酸蛋白酶，可切割粘连蛋白的 Scc1 亚基，粘连蛋白是一种复杂的蛋白质，在物理上连接姐妹染色单体并在有丝分裂纺锤体动力学中发挥重要作用。该提案将最近描述的肽变形技术应用于合理设计和合成小非肽分子以结合和抑制分离酶。我们希望该提案能够通过向具有紧急生物学兴趣和意义的蛋白质靶标呈现功能丰富且立体多样化的配体结构来展示肽变形的力量。分离酶的抑制，特别是在活性位点的抑制，应该能够揭示染色体生物学的关键方面。