Excellence in Research: Evaluating thiol-peptides with auxiliary binding groups as chelators of mercury(II)

卓越研究：评估带有辅助结合基团的硫醇肽作为汞螯合剂 (II)

• 批准号: 1831020
• 负责人: Maria Ngu-Schwemlein
• 金额: $ 32.87万
• 依托单位: Winston-Salem State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1831020&HistoricalAwards=false
• 关键词: Excellence; Research; Evaluating; thiol; peptides

In this project, co-funded by the Historically Black Colleges and Universities Undergraduate program and the Chemical Structure, Dynamic and Mechanism B program, Professor Maria Ngu-Schwemlein and her collaborator Dr. John Merle, of the Chemistry Department at Winston Salem State University are developing eco-friendly biomolecules to sequester toxic mercury ions. The goal of this project is to design effective thiol-peptides to immobilize mercury ions for applications in environmental remediation of mercury polluted water, and as sensors or reporters of mercury ions. It may also afford a basis for future research in developing genetically engineered plants that are useful for phytoremediation. This project lies at the interface of bioorganic, inorganic, analytical, and computational chemistry, and therefore provides an excellent breadth of education for scientists and students. The project activities also provide a high level of education and research training to prepare undergraduates, primarily underrepresented groups at this historically black university, for entry into advanced degree programs and careers in science. Peptides offer inherent high affinities for their targets due to the versatility of its monomeric units, which offer a wide variety of donor atoms and contribute to specific secondary structures. The proposed syntheses include thiol-peptides with different auxiliary binding groups to evaluate complex formation with mercury(II) and to assess for enhanced mercury(II) immobilization through increased complex stability. In this project, oligopeptides consisting of di- or multi-cysteinyl residues with added auxiliary groups (O-, N-, or aromatic pi donors) are prepared to answer the following questions: (1) How do multi-thiol peptides containing different auxiliary donors form complexes with mercury(II)? (2) Can auxiliary binding groups form significant binding specificities resulting in sterically hindered peptide-mercury complexes that are kinetically stable? (3) What is the significance and stability of type II beta turn in cysteinyl peptides for binding mercury(II)? (4) What are the spatial accessibilities in these peptide ligands that can be identified for chemical conjugation with carriers or fluorophores for immobilizing and sensing mercury(II)? The findings from this study could be useful for developing effective chelators of mercury(II) for applications in environmental remediation, human health protection, and sensing.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.

在这个项目中，由历史悠久的黑人学院和大学本科课程以及化学结构，动态和机制B计划，Winston Salem State University化学系的合作者Maria Ngu-Schwemlein教授和她的合作者John Merle博士共同资助。 该项目的目的是设计有效的硫醇肽，以将汞离子固定在汞污染水的环境修复中，并作为汞离子的传感器或记者。 它还可以为未来的研究提供基础研究的基础，以开发对植物修复有用的基因工程植物。 该项目位于生物有机，无机，分析和计算化学的界面，因此为科学家和学生提供了极好的教育广度。 该项目活动还提供了高水平的教育和研究培训，以准备这所历史悠久的黑人大学的本科生，主要是代表性不足的群体，以进入科学领域的高级学位课程和职业。 由于其单体单元的多功能性，肽为其目标提供了固有的高亲和，这些单元提供了各种各样的供体原子，并为特定的二级结构做出了贡献。 所提出的合成包括具有不同辅助结合基团的硫醇肽，以评估与汞（II）的复合形成，并通过提高复杂稳定性来评估增强的汞（II）固定。 在该项目中，准备通过添加的辅助组（O-，N-或芳香族PI供体）组成的二或多囊样残基组成的寡肽可以回答以下问题：（1）含有不同辅助供体的多硫醇肽如何形成与Mercury（Mercury）形成复合物（II）？ （2）辅助结合基部可以形成显着的结合特异性，从而导致在动力学上稳定的肽 - 粘液菌络合物？ （3）在结合汞（II）中，II型β型转弯的意义和稳定性是什么？ （4）这些肽配体中有哪些空间可访问性可以鉴定出与载体或荧光团化学结合以固定和传感汞（ii）的化学结合？这项研究的发现对于开发汞（II）的有效螯合剂（II）可能很有用，用于在环境修复，人类健康保护和感应中的应用。该奖项反映了NSF的法定任务，并认为值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来进行评估。

项目成果

Dithiolated peptides incorporating bis(tryptophan)s for cooperative mercury(II) binding

掺入双（色氨酸）的二硫醇化肽可协同结合汞（II）

• DOI: 10.1016/j.bmc.2021.116296
• 发表时间: 2021
• 期刊: Bioorganic & Medicinal Chemistry
• 影响因子: 3.5
• 作者: Ngu-Schwemlein, Maria;Merle, John;Cameron, T'ea;Witcher, Charlexia;Todd, Daniel
• 通讯作者: Todd, Daniel

Evaluating the involvement of tryptophan on thiolated peptide-mercury(II) complexes: Cation-pi interactions

• DOI: 10.1016/j.ica.2020.119552
• 发表时间: 2020-06-01
• 期刊: INORGANICA CHIMICA ACTA
• 影响因子: 2.8
• 作者: Ngu-Schwemlein, Maria;Merle, John;Nixon, Timothy
• 通讯作者: Nixon, Timothy