Synthesis and Screening of Peptide and Protein Based Rhenium Carbonyl Compounds a

描述(由申请人提供)：本申请的目标是继续研究REI(CO)3化合物作为下一代Tc/Re放射性核素剂的模型。随着在我们之前的资助期间发现了特定的多肽和蛋白质相互作用，我们将把注意力转移到下一个计划期的这种化学上。我们有兴趣通过Re(CO)3(H2O)3+离子与多肽和蛋白质的直接相互作用来开发靶向的REI(CO)3化合物，这与传统的双功能螯合剂(BFCA)方法不同。具体地说，我们希望1)研究Re(CO)3(H2O)3+离子与多肽之间的相互作用，扩展我们在组氨酸方面的工作，包括半胱氨酸和蛋氨酸以及吡啶亚胺偶联氨基酸；2)筛选一个强REI(CO)3结合肽文库以辅助His-tag序列的设计；3)通过His-tag(Rna 15)用REI(CO)3修饰蛋白质，用REI(CO)3(胰岛素和碳酸氢酶)取代三组氨酸锌位点，以及设计一个REI(CO)3结合位点(天青素)。这项工作将主要在阿克伦大学克里斯托弗·J·齐格勒教授的实验室进行，但圣十字学院的理查德·赫里克教授将提供大量帮助。该项目将在项目期间每年支持两名博士研究生和两名本科生的培训。该提案的资金还将用于在计划期间的夏季期间支持PI(每年一个月)。研究生将专攻生化和无机方法；本科生将由研究生在这些领域进行培训。 公共卫生相关性：这项工作在几个方面与公共卫生相关。首先，这项研究将直接有助于开发针对特定组织的新型氚放射性药物。基于氚的显像剂是目前临床上使用的最常见的放射性核素，对脑、心血管和骨骼结构的成像至关重要。此外，这笔补助金将帮助培训研究生和本科生，这些学生将继续在与健康有关的专业工作。

DESCRIPTION (provided by applicant): The objective of this application is the continued investigation of ReI(CO)3 compounds as models for next generation Tc/Re radionuclide agents. With the discovery of specific peptide and protein interactions during our previous grant period, we are moving our attention to this chemistry for the next program period. We are interested in developing targeted ReI(CO)3 compounds via the direct interaction of the Re(CO)3(H2O)3+ ion with polypeptides and proteins, which represents a departure from the traditional bifunctional chelate agent (BFCA) approach. Specifically, we wish to 1) Investigate the interactions between the Re(CO)3(H2O)3+ ion and peptides, extending our work on histidine and including cysteine and methionine as well as pyridine imine coupled amino acids, 2) Screen a peptide library for strong ReI(CO)3 binders to assist with the design of his-tag sequences, 3) modify proteins with ReI(CO)3 through his-tags (rna15), replacement of tris-histidine zinc sites with ReI(CO)3 (insulin and carbonic anhydrase) and the engineering of a ReI(CO)3 binding site (azurin). This work will be carried out primarily in the laboratories of Prof. Christopher J. Ziegler at the University of Akron, but significant assistance will come from Prof. Richard Herrick at the College of the Holy Cross. This project will support the training of two Ph.D. graduate students during the program period as well as two undergraduate researchers per year. Funds from the proposal will also be used to support the PI (one month per year) during the summers of the program period. The graduate students will be specialized in biochemical and inorganic methods; the undergraduate students will be trained in these areas by the graduate students. PUBLIC HEALTH RELEVANCE: This work is relevant to public health in several ways. First, this research will directly contribute to the development of new technetium radiopharmaceuticals that target specific tissues. Technetium-based imaging agents are the most common radionuclides in use in the clinic today, and are crucial for the imaging of brain, cardiovascular and skeletal structures. In addition, this grant will assist in the training of both graduate and undergraduate students who will go on to work in health related professions.