Libraries of Template-Constrained Cyclic Peptides

模板限制的环肽文库

• 批准号: 9634646
• 负责人: William DeGrado
• 金额: $ 39.13万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9634646&HistoricalAwards=false
• 关键词: Libraries; Template; Constrained; Cyclic; Peptides

The focus of this research is to develop a combinatorial approach to lock a given short peptide sequence into a variety of different conformations. The sequence of interest is then incorporated into a macrocycle containing a template that serves as a conformational tuning element. The conformational properties of the template molecule influence the conformation of the intervening tetrapeptide sequence thus affording a template-constrained cyclic peptide. The potential target peptides will use two tripeptide sequences, Arg-Gly-Asp (RGD) and Leu-Asp-Val (LDV) which are recognized by the cell adhesion integrins. With this GOALI award, the Office of Multidisciplinary Activities and the Synthetic Organic Program are supporting the research of Dr. William F. DeGrado of the Department of Biochemistry and Biophysics at the University of Pennsylvania and Dr. Mark A. Scialdone of DuPont Central Research and Development. The team will focus on developing methodologies for the presentation of peptides in a variety of coformational states. These methods should have use for the design and synthesis of peptide mimetics that inhibit a variety of peptide/protein and protein/protein interactions. Such compounds might be useful directly as pharmaceuticals, diagnostics or agricultural products.

这项研究的重点是开发一种组合方法，将给定的短肽序列锁定为多种不同的构象。 然后将感兴趣的序列掺入含有模板的大环中，该模板用作构象调节元件。 模板分子的构象特性影响插入的四肽序列的构象，从而提供模板限制的环肽。 潜在的目标肽将使用两个三肽序列，Arg-Gly-Asp (RGD) 和 Leu-Asp-Val (LDV)，它们可被细胞粘附整联蛋白识别。 凭借这一 GOALI 奖，多学科活动办公室和合成有机项目正在支持宾夕法尼亚大学生物化学和生物物理学系的 William F. DeGrado 博士和杜邦中央研究与开发部的 Mark A. Scialdone 博士的研究。 该团队将专注于开发以各种构象状态呈现肽的方法。 这些方法应该可用于抑制各种肽/蛋白质和蛋白质/蛋白质相互作用的肽模拟物的设计和合成。 此类化合物可直接用作药物、诊断剂或农产品。