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Adding New Covalent Bonds to Proteins in Live Cells

在活细胞中的蛋白质中添加新的共价键

基本信息

批准号：
9264558
负责人：
Lei Wang
金额：
$ 28.57万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-20 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9264558
关键词：
Amino Acids Biological Biological Process Biological Response Modifier Therapy Biology Biotechnology Cell physiology Cells Chemicals Chemistry Cysteine Dependence Dimensions Disease Engineering Environment Event G-Protein-Coupled Receptors Genetic Genetic Code Ligands Light Location Mammalian Cell Methods Nucleic Acids Optics Oxidation-Reduction Peptides Physiological Play Property Protein Biosynthesis Protein Engineering Proteins Reaction Recombinants Research Resolution Role Side Signal Transduction Site Specificity Structure Technology Testing Translations Ultrafine Vertebral column azobenzene chemical function covalent bond cytotoxicity design disulfide bond in vivo innovation microwave electromagnetic radiation nano novel peptide drug protein function protein structure public health relevance success synthetic biology therapeutic protein tool unnatural amino acids

项目摘要

DESCRIPTION (provided by applicant): Proteins are basic building blocks and workhorses of biology. A fundamental limitation of proteins is their inadequacy in covalent bonding via side chains. This application will break this natural barrier by genetically introducing new covalent bonds into proteins in live cells. The principle of the approach is to use a novel amino acid to react with natural amino acid residues in proteins. However, huge challenges are imposed by the contradictory demands on bioreactivity, genetic encoding, and specificity of bond formation. Our hypothesis and innovation is to enable the new amino acid to react with the target natural amino acid only when they are in proximity, thus permitting building the new covalent bond in proteins in live cells. New chemistries suitable for such reactions under physiological conditions will be developed. The identified chemical functionality will be installed into proteins in the format of new amino acids through protein translation in live cells. Using this new covalent bonding strategy, we will build light-sensitive nano-bridges onto proteins as a general method to optically regulate protein function for noninvasive studies in cells and in vivo. In the long run, e will further develop these new covalent bonds for studying protein networks and protein-nucleic acid interactions involved in various diseases and for generating new protein therapeutics. The success of this project will lead to a new dimension for researching and engineering proteins and biological processes by harnessing the new covalent linkages inaccessible to natural proteins, fundamentally impacting basic biological studies, biotechnology, biotherapeutics, and synthetic biology.