Utilization of Unnatural Amino Acids in de novo Protein Synthesis

该研究将开发一种新的蛋白质合成方法，该方法基于超二级结构基序的组装，通过掺入特别设计的非天然氨基酸残基来稳定蛋白质。多肽中非天然氨基酸残基的合成、掺入和结构表征是研究的关键要素。残基将用作约束β - II型反转的基础。此外，通过提供比目前可用的更多的β支链氨基酸残基选择，非天然氨基酸残基应该有助于建立β片结构。该研究建议利用超二级（而不是三级）结构元素作为蛋白质设计的基本构建块，以促进预测和分析过程。进一步功能化的非天然残留物可以形成生产新的调节或催化生物聚合物的基础。有了这个有机合成项目的奖项，加州理工学院化学系的芭芭拉·Imperiali博士将在从头合成蛋白质领域进行研究。该研究将集中于开发可以以合理方式组装的构建块，以提供具有预定三维结构的蛋白质产品。Imperiali博士将使用基于非天然氨基酸残基的肽基化合物，这种化合物可用于构建新的蛋白质。进一步功能化的非天然残留物可以导致生产新的调节或催化生物聚合物。

The research will develop an approach to de novo protein synthesis which is based on the assembly of supersecondary structural motifs stabilized by the incorporation of specifically designed unnatural amino acid residues. Synthesis, incorporation and structural characterization of unnatural amino acid residues within polypeptides are crucial elements of the research. The residues will be used as the basis for constrained beta-type II reverse turns. Further, the unnatural amino acid residues should help in establishing beta-sheet stucture by providing a greater choice of beta-branched amino acid residues than that currently available. The research proposes utilization of supersecondary (rather than tertiary) structural elements as the basic building blocks in protein design to facilitate both predictive and analytical processes. Further functionalization of the unnatural residues can form the basis for the production of new regulatory or catalytic biopolymers. %%% With this award from the Synthetic Organic Program, Dr. Barbara Imperiali of the Department of Chemistry at the California Institute of Technology will conduct research in the area of de novo protein synthesis. The research will focus on developing building blocks which can be assembled in a rational manner to afford proteinaceous products with a predetermined three-dimensional structure. Dr. Imperiali will use peptidyl compounds, based on unnatural amino acid residues, which can be used to build new proteins. Further functionalization of the unnatural residues can lead to the production of new regulatory or catalytic biopolymers.