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

在这个项目中，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博士共同资助了历史上的黑人学院和大学本科项目以及化学结构、动态和机制B项目，他们正在开发环保生物分子来隔离有毒汞离子。本项目的目标是设计有效的硫醇肽来固定化汞离子，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。这也可能为未来开发对植物修复有用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界处，因此为科学家和学生提供了极好的教育广度。项目活动还提供高水平的教育和研究培训，为本科生进入高级学位课程和科学职业生涯做好准备。在这所历史悠久的黑人大学，本科生主要是代表不足的群体。由于其单体单元的多功能性，多肽为其目标提供了固有的高亲和力，这些单体单元提供了各种各样的给体原子，并对特定的二级结构做出了贡献。建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)的络合物的形成，并通过增加络合物的稳定性来评估增强汞(II)的固定化。在本项目中，由二或多个半胱氨基残基组成的寡肽加上辅助基团(O-，N-，或芳香族pi供体)准备回答以下问题：(1)含有不同辅助供体的多个硫醇肽如何与汞(II)形成络合物？(2)辅助结合基团是否能形成显著的结合特异性，从而形成动力学稳定的空间受阻的多肽-汞络合物？(3)半胱氨酸多肽中II型β转角对结合汞(II)的意义和稳定性是什么？(4)这些多肽配体中哪些空间可与载体或荧光团化学结合以固定和传感汞(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、人类健康保护和感官应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.