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)

基本信息

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

项目摘要

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，由历史黑人学院和大学本科项目和化学结构、动力学和机制 B 项目共同资助，温斯顿塞勒姆州立大学化学系的 Maria Ngu-Schwemlein 教授和她的合作者 John Merle 博士开发环保生物分子来隔离有毒汞离子。该项目的目标是设计有效的硫醇肽来固定汞离子，用于汞污染水的环境修复，并作为汞离子的传感器或报告器。它还可以为未来开发可用于植物修复的基因工程植物的研究提供基础。该项目位于生物有机化学、无机化学、分析化学和计算化学的交叉领域，因此为科学家和学生提供了广泛的教育。该项目活动还提供高水平的教育和研究培训，为本科生（主要是这所历史悠久的黑人大学中代表性不足的群体）做好进入高级学位课程和科学职业的准备。由于其单体单元的多功能性，肽对其靶标具有固有的高亲和力，这些单体单元提供了多种供体原子并有助于形成特定的二级结构。拟议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）的复合物形成，并评估通过增加复合物稳定性来增强汞（II）固定。本项目制备了由双或多半胱氨酰残基添加辅助基团（O-、N-或芳香π供体）组成的寡肽，以回答以下问题：（1）含有不同辅助基团的多硫醇肽如何供体与汞(II)形成络合物？ (2) 辅助结合基团能否形成显着的结合特异性，从而产生动力学稳定的空间位阻肽-汞复合物？ (3) 半胱氨酰肽中II型β转角对于结合汞(II)的意义和稳定性是什么？ (4) 这些肽配体的空间可及性是什么，可以识别这些肽配体与载体或荧光团的化学缀合，以固定和感测汞(II)？这项研究的结果可能有助于开发有效的汞（II）螯合剂，用于环境修复、人类健康保护和传感等领域。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持以及更广泛的影响审查标准。