New Amino Acids for Protein Engineering

用于蛋白质工程的新氨基酸

基本信息

批准号：
7283057
负责人：
DAVID A TIRRELL
金额：
$ 32.39万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-01-01 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7283057
关键词：
Address Alkynes Amino Acids Amino Acids Activation Amino Acyl-tRNA Synthetases Attention Award Azides Binding Biocompatible Materials Cells Chemicals Chemistry Codon Nucleotides Collaborations Complement Development Engineering Evaluation Exhibits Extracellular Matrix Proteins Genetic Transcription In Vitro Isoleucine Ketones Kinetics Laboratories Leucine Ligase Liquid substance Measurement Messenger RNA Methionine Methods Mutagenesis Natural regeneration Phase Phenylalanine Phenylalanine-tRNA Ligase Post-Translational Protein Processing Progress Reports Protein Engineering Proteins Protocols documentation Recombinant Proteins Request for Applications Research Research Personnel Sense Codon Side Site Solid Substrate Specificity Synthetic Genes System Tissues Translations Tyrosine Tyrosine-tRNA Ligase Valine Variant Work analog crosslink design engineering design functional group in vivo leucyl-isoleucyl liquid crystal macromolecule method development mutant novel phenylalanine analog physical property programs reconstruction research study tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): This application requests support for the development of new methods for the incorporation of novel amino acids into recombinant proteins. Computational and experimental studies will be combined to design mutant forms of the aminoacyl-tRNA synthetases that are capable of efficient activation of amino acid analogs bearing reactive functional groups. Special attention will be given to amino acids that carry alkyne, azide and ketone functional groups, in order to provide powerful new chemistries for use in the engineering of natural and artificial proteins. Computational design will be evaluated in comparison with experimental approaches that involve multiple rounds of mutagenesis and selection, and computational predictions will be assessed by comparison with the results of in vitro kinetic studies of amino acid activation. Cell free transcription - translation systems will be used as appropriate to identify and address limitations due to poor amino acid transport. The new chemistries to be developed in this work will open new opportunities in the design of engineered biomaterials.

描述（由申请人提供）：此申请要求支持开发新方法，以将新型氨基酸掺入重组蛋白中。计算和实验研究将结合到设计能够有效激活具有反应官能团的氨基酸类似物的氨基酰基-TRNA合成酶的突变形式。将特别注意携带炔烃，叠氮基和酮功能组的氨基酸，以便提供有力的新化学物质，用于在天然和人造蛋白的工程中使用。与涉及多个诱变和选择的实验方法相比，将评估计算设计，并通过与氨基酸激活的体外动力学研究结果进行评估计算预测。无细胞转录 - 将适当地使用翻译系统，以识别和解决由于氨基酸运输差而引起的局限性。这项工作中要开发的新化学物质将在设计生物材料的设计方面为新的机会开放。