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

在这个项目中，由历史悠久的黑人学院和大学本科项目和化学结构，动态和机制B项目共同资助，温斯顿塞勒姆州立大学化学系的Maria nung - schwemlein教授和她的合作者John Merle博士正在开发环保生物分子来隔离有毒的汞离子。本课题的目的是设计有效的巯基肽固定汞离子，用于汞污染水体的环境修复，并作为汞离子的传感器或报告器。这也为今后开发可用于植物修复的基因工程植物奠定了基础。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一个极好的教育广度。项目活动还提供了高水平的教育和研究培训，为本科生（在这所历史悠久的黑人大学中主要是代表性不足的群体）进入高级学位课程和科学职业做好准备。由于其单体单位的多功能性，多肽为其目标提供了固有的高亲和力，其提供了各种各样的供体原子并有助于特定的二级结构。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）的配合物形成，并评估通过增加配合物的稳定性来增强汞（II）的固定化。在这个项目中，由二或多半胱氨酸残基与添加辅助基团（O-， N-或芳香pi给体）组成的寡肽被制备来回答以下问题：(1)含有不同辅助给体的多硫醇肽如何与汞（II）形成配合物？(2)辅助结合基团能否形成显著的结合特异性，从而形成具有动力学稳定性的位阻肽-汞配合物？(3)结合汞（II）的半胱氨酸肽II型β转化的意义和稳定性是什么？(4)这些肽配体的空间可达性是什么？这些肽配体可以与载体或荧光团进行化学偶联，以固定和感应汞（II）？本研究结果可用于开发有效的汞螯合剂，用于环境修复、人体健康保护和传感。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。

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.