Synthesis and Applications of functional Macromolecules

功能高分子的合成及应用

• 批准号: 7336332
• 负责人: Christian E Schafmeister
• 金额: $ 25.28万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7336332
• 关键词: Active Sites; Amides; Amino Acids; Antibodies; Binding; Biological; Biomimetics; Catalysis; Catalytic RNA; Chemicals; Chemistry; Complex; Computer information processing; Development; Devices; Dimensions; Exercise; Fluorescence Resonance Energy Transfer; Free Energy; Goals; Learning; Libraries; Life; Measurement; Measures; Molecular; Molecular Weight; Nature; Object Attachment; Peptides; Phage Display; Pliability; Process; Proteins; RNA Folding; Range; Series; Shapes; Side; Solid; Solutions; Structure; Structure-Activity Relationship; Technology; Testing; catalyst; cavitand; chemical function; design; design and construction; functional group; interest; macromolecule; monomer; nanoscale; new technology; novel; peptide structure; prototype; receptor binding; scaffold; three dimensional structure; time use; tool

DESCRIPTION (provided by applicant): Nature relies on structured macromolecules in the form of proteins and catalytic RNA's that fold into specific three-dimensional structures and present reactive functionality in precise constellations in order to carry out the chemical processes of life. The structured nature of these molecules and what we have learned from proteins about structure/function relationships suggests that given the ability to construct macromolecules and control their three-dimensional structures, we could develop macromolecules with biomimetic capabilities and with entirely new chemical functions. Our goal is to develop a novel, basic technology for synthesizing macromolecules with designed three-dimensional shapes and capable of presenting multiple chemically reactive groups in controlled ways to perform new functions. Our approach is to synthesize small, rigid molecular building blocks (bis-amino acids) and couple them through pairs of amide bonds to create ladder oligomers. Each monomer contains multiple stereocenters that are set in the building block synthesis. The bis-amino acids are assembled on solid support, or in solution, in specific sequences to form constitutionally precise macromolecules with specific structures. We propose the following specific goals. 1) We will utilize our prototype monomer to synthesize several scaffolds with interesting structures and determine their structures. 2) We will measure the flexibility of linear and bow-shaped scaffolds. 3) We will develop syntheses of additional monomers. 4) We will synthesize macromolecules that display cavities with dimensions comparable to those of protein active sites and determine their structures. 5) We will discover peptides that selectively bind these cavitand scaffolds and characterize the interaction through structure determination and measurement of binding free energies. 6) We will develop syntheses for bis-amino acids that display an additional functional group akin to the side chain of an amino acid. 7) We will develop a general approach to the design of complex functional group arrays that are capable of biomimetic function and could be used for the development of nanoscale molecular devices.

描述(申请人提供)：自然界依赖于蛋白质和催化RNA形式的结构化大分子，这些大分子折叠成特定的三维结构，并在精确的星座中呈现反应功能，以执行生命的化学过程。这些分子的结构性质以及我们从蛋白质中了解到的结构/功能关系表明，如果我们有能力构建大分子并控制其三维结构，我们就可以开发出具有仿生能力和全新化学功能的大分子。我们的目标是开发一种新颖的基础技术，用于合成具有设计的三维形状的大分子，并能够以受控的方式呈现多个化学反应基团来执行新的功能。我们的方法是合成小的、刚性的分子构建块(双-氨基酸)，并通过成对的酰胺键将它们偶联，生成梯形低聚物。每个单体包含设置在构建块合成中的多个立体中心。双-氨基酸在固体载体上或在溶液中以特定的序列组装，形成具有特定结构的构成上精确的大分子。我们提出了以下具体目标。1)我们将利用我们的原型单体合成几种具有有趣结构的支架，并确定它们的结构。2)测量直线脚手架和弓形脚手架的挠度。3)我们将开发更多单体的合成。4)我们将合成具有与蛋白质活性中心相当大小的空腔的大分子，并确定其结构。5)我们将发现选择性结合这些空穴和支架的多肽，并通过结构测定和结合自由能的测量来表征相互作用。6)我们将开发具有类似于氨基酸侧链的附加官能团的双氨基酸的合成。7)我们将开发一种通用的方法来设计具有仿生功能的复杂功能基团阵列，并可用于开发纳米级分子器件。