Peptide Stapling Using Conformationally Constrained Building Blocks
使用构象约束构建模块进行肽缝合
基本信息
- 批准号:2003010
- 负责人:
- 金额:$ 35.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Joshua Kritzer of Tufts University to develop new chemical building blocks that control the shape of peptides to mimic distinct conformations seen in proteins. Peptides are short polymer chains of amino acids that share many properties with larger proteins. The ability to control the three-dimensional shape or conformation of peptides allows the control of these properties and, consequently, their functions. In this project, chemical tethers are used to link an unnatural amino acid (one that is not found in terrestrial organisms) to another amino acid along the chain to constrain the shape of the peptide. The resulting peptides have potential applications in materials science, as catalysts and in drug development. In addition, the project prepares students to enter the science workforce through the development of a series of training workshops that help students practice professional skills, provide career guidance, and promote diversity and inclusion.The research project employs a new strategy for side-chain-mediated cross-linking, or “stapling,” that takes advantage of the unique conformational properties of the unnatural amino acid 4-mercaptoproline. Multiple independent strategies are used to incorporate 4-mercaptoproline staples into peptides, producing unique varieties of stapled beta-hairpins, stapled collagen-like helices and assemblies, and stapled bicyclic peptides. The three-dimensional structures of these designed structural scaffolds are determined by solution-state NMR spectroscopy. The effects of the new staples on biological degradation and cell penetration are examined through cell-based assays. The long term broader scientific impact of this work is to provide tools and methodology to control peptide architecture and biological stability and in so doing construct polypeptides with particular utility for studies in chemical biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
该奖项将资助塔夫茨大学(Tufts University)的Joshua Kritzer博士开发新的化学构建模块,以控制肽的形状,模拟蛋白质中的不同构象。肽是由氨基酸组成的短聚合物链,与较大的蛋白质具有许多相同的特性。控制肽的三维形状或构象的能力允许控制这些特性,从而控制它们的功能。在这个项目中,化学链被用来将一种非天然氨基酸(在陆生生物中没有发现的氨基酸)连接到另一种氨基酸上,以限制肽的形状。由此产生的肽在材料科学、催化剂和药物开发方面具有潜在的应用前景。此外,该项目还通过开发一系列培训讲习班,帮助学生练习专业技能,提供职业指导,促进多样性和包容性,为学生进入科学队伍做好准备。该研究项目采用了侧链介导交联或“钉接”的新策略,该策略利用了非天然氨基酸4-巯基脯氨酸的独特构象特性。采用多种独立的策略将4-巯基脯氨酸钉入肽中,产生独特品种的钉接β -发夹,钉接胶原样螺旋和组装,以及钉接双环肽。所设计的结构支架的三维结构通过溶液态核磁共振谱测定。新钉对生物降解和细胞渗透的影响是通过基于细胞的分析来检查的。这项工作的长期更广泛的科学影响是提供控制肽结构和生物稳定性的工具和方法,并在此过程中构建具有化学生物学研究特殊用途的多肽。该奖项反映了美国国家科学基金会的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Joshua Kritzer其他文献
Joshua Kritzer的其他文献
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{{ truncateString('Joshua Kritzer', 18)}}的其他基金
Understanding the roles of conformational constraints in functional phosphotyrosine mimics
了解构象限制在功能性磷酸酪氨酸模拟物中的作用
- 批准号:
1507456 - 财政年份:2015
- 资助金额:
$ 35.7万 - 项目类别:
Continuing Grant
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