Selection of Modified Ribosomes Using Novel Puromycins

使用新型嘌呤霉素选择修饰核糖体

• 批准号: 10061609
• 负责人: Sidney M. Hecht
• 金额: $ 26.69万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-13 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10061609
• 关键词: Amino Acids; Amino Acyl Transfer RNA; Antiviral Agents; Bacterial Proteins; Behavior; Binding; Biochemical; Carbohydrates; Cell Death; Cells; DNA; DNA Repair; DNA biosynthesis; DNA-Binding Proteins; Derivation procedure; Dipeptides; Escherichia coli; Excision; Goals; Grant; In Vitro; Interferon-beta; Laboratories; Libraries; Mass Spectrum Analysis; Modification; Mus; Organism; Peptidyltransferase; Phosphorylation; Phosphotyrosine; Plasmids; Play; Positioning Attribute; Preparation; Production; Prokaryotic Cells; Property; Protein Biosynthesis; Proteins; Puromycin; RNA, Ribosomal, 23S; Reporting; Research; Research Design; Ribosomal RNA; Ribosomes; Role; SS DNA BP; Site; Structure; System; Transfer RNA; Tyrosine; Virulence; analog; cost; experimental study; functional group; inorganic phosphate; interest; link protein; novel; protein function; sugar; unnatural amino acids; virtual

Project Summary The long term goals of this research involve modification of the peptidyltransferase (PTC) center in bacterial ribosomes to enable the incorporation of very unusual amino acids not recognized by wild- type ribosomes. In recent years, we have described the selection of modified ribosomes and their use in incorporating D-amino acids, beta amino acids, dipeptides and dipeptidomimetric cassettes into proteins. During the four years of proposed research, the focus of efforts will be on the selection of ribosomes capable of introducing phosphorylated and glycosylated amino acids into specific proteins. The utility of this approach will be explored by analyzing the altered function of proteins into which phosphates and carbohydrates have been introduced, and by expressing a phosphorylated DNA binding protein in E. coli.

项目摘要 这项研究的长期目标涉及修改肽基转移酶（PTC）中心 细菌核糖体能够掺入野生识别的非常异常的氨基酸 型核糖体。近年来，我们描述了修饰的核糖体的选择及其使用 在将D-氨基酸，β氨基酸，二肽和二肽米的盒中掺入中 蛋白质。在拟议的四年研究中，努力的重点将是选择 能够将磷酸化和糖基化氨基酸引入特定蛋白质的核糖体。 通过分析蛋白质的功能改变的功能，将探索这种方法的实用性 引入了磷酸盐和碳水化合物，并通过表达磷酸化的DNA 大肠杆菌中的结合蛋白。

项目成果

Protein Synthesis with Ribosomes Selected for the Incorporation of β-Amino Acids.

• DOI: 10.1021/acs.biochem.5b00389
• 发表时间: 2015-06-16
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Maini, Rumit;Chowdhury, Sandipan Roy;Dedkova, Larisa M.;Roy, Basab;Daskalova, Sasha M.;Paul, Rakesh;Chen, Shengxi;Hecht, Sidney M.
• 通讯作者: Hecht, Sidney M.

Synthesis and Evaluation of a Library of Fluorescent Dipeptidomimetic Analogues as Substrates for Modified Bacterial Ribosomes.

• DOI: 10.1021/acs.biochem.6b00102
• 发表时间: 2016-05-03
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Chowdhury SR;Chauhan PS;Dedkova LM;Bai X;Chen S;Talukder P;Hecht SM
• 通讯作者: Hecht SM

Enhanced Binding Affinity for an i-Motif DNA Substrate Exhibited by a Protein Containing Nucleobase Amino Acids.

• DOI: 10.1021/jacs.6b11825
• 发表时间: 2017-04-05
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Bai X;Talukder P;Daskalova SM;Roy B;Chen S;Li Z;Dedkova LM;Hecht SM
• 通讯作者: Hecht SM

Ribosome-Mediated Incorporation of Dipeptides and Dipeptide Analogues into Proteins in Vitro.

• DOI: 10.1021/jacs.5b03135
• 发表时间: 2015-09-09
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Maini R;Dedkova LM;Paul R;Madathil MM;Chowdhury SR;Chen S;Hecht SM
• 通讯作者: Hecht SM

Synthesis of alanyl nucleobase amino acids and their incorporation into proteins.

• DOI: 10.1016/j.bmc.2016.07.008
• 发表时间: 2016-09-15
• 期刊: Bioorganic & medicinal chemistry
• 影响因子: 3.5
• 作者: Talukder P;Dedkova LM;Ellington AD;Yakovchuk P;Lim J;Anslyn EV;Hecht SM
• 通讯作者: Hecht SM