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

肽和蛋白质基铼羰基化合物的合成与筛选

基本信息

批准号：
8367543
负责人：
CHRISTOPHER J ZIEGLER
金额：
$ 34.5万
依托单位：
UNIVERSITY OF AKRON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8367543
关键词：
Amines Amino Acids Area Attention Azurin Binding Binding Sites Biochemical Brain imaging Cardiovascular system Chelating Agents Chemicals Chemistry Clinic Complex Coupled Cysteine Development Diagnostic Doctor of Philosophy Egg White Elements Engineering Frequencies Funding Grant Health Histidine Image Imidazole Imines Insulin Intention Investigation Ions Label Laboratories Libraries Ligation Lysine Metalloproteins Metals Methionine Methods Modeling Mono-S Muramidase Peptide Library Peptide Synthesis Peptides Peripheral Phase Positioning Attribute Post-Translational Protein Processing Protein Region Proteins Public Health Publishing Radioisotopes Radiopharmaceuticals Reaction Reagent Reporting Research Research Personnel Rhenium Schiff Bases Screening procedure Side Site Site-Directed Mutagenesis Solid Stretching Structure System Technetium Tissues Training Training Support Universities Work Zinc adduct base carbonate dehydratase carbonyl compound college cupredoxin design functional group graduate student interest molecular assembly/self assembly next generation polypeptide programs protein complex pyridine skeletal undergraduate student

项目摘要

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.

描述（由申请人提供）：本申请的目的是继续研究 ReI(CO)3 化合物作为下一代 Tc/Re 放射性核素试剂的模型。随着我们在上一个资助期间发现特定的肽和蛋白质相互作用，我们将在下一个项目期间将注意力转向这种化学。我们感兴趣的是通过 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 ReI(CO)3 化合物，这代表了传统双功能螯合剂 (BFCA) 方法的背离。具体来说，我们希望 1) 研究 Re(CO)3(H2O)3+ 离子和肽之间的相互作用，扩展我们对组氨酸的工作，包括半胱氨酸和蛋氨酸以及吡啶亚胺偶联氨基酸，2) 筛选肽用于强 ReI(CO)3 结合物的文库，以协助设计 his 标签序列，3) 通过 his 标签 (rna15) 用 ReI(CO)3 修饰蛋白质，替换具有 ReI(CO)3（胰岛素和碳酸酐酶）的三组氨酸锌位点以及 ReI(CO)3 结合位点（天青蛋白）的工程设计。这项工作将主要在阿克伦大学 Christopher J. Ziegler 教授的实验室中进行，但圣十字学院的 Richard Herrick 教授将提供重要协助。该项目将支持培养两名博士生。项目期间的研究生以及每年两名本科生研究人员。该提案的资金还将用于在项目期间的夏季支持 PI（每年一个月）。研究生将专门研究生物化学和无机方法；研究生将在这些领域对本科生进行培训。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锝放射性药物。锝基成像剂是当今临床中最常用的放射性核素，对于大脑、心血管和骨骼结构的成像至关重要。此外，这笔赠款将有助于培训将继续从事健康相关专业工作的研究生和本科生。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The synthesis and structures of 1,1'-bis(sulfonyl)ferrocene derivatives.

DOI：
10.1039/c6dt02669a
发表时间：
2016-09-28
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
0
作者：
Chanawanno K;Holstrom C;Crandall LA;Dodge H;Nemykin VN;Herrick RS;Ziegler CJ
通讯作者：
Ziegler CJ

Facile solid phase peptide synthesis with a Re-lysine conjugate generated via a one-pot procedure.

通过一锅法生成 Re-赖氨酸缀合物，轻松进行固相肽合成。

DOI：
10.1039/c4dt01129e
发表时间：
2014
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
0
作者：
Chanawanno,Kullapa;Caporoso,Joel;Kondeti,Vinay;Paruchuri,Sailaja;Leeper,ThomasC;Herrick,RichardS;Ziegler,ChristopherJ
通讯作者：
Ziegler,ChristopherJ

New 1,1'-Ferrocene Bis(sulfonyl) Reagents.