Exploring Aromatic Donor-Acceptor Interactions in Water

探索水中芳香族供体-受体相互作用

• 批准号: 7175452
• 负责人: BRENT L IVERSON
• 金额: $ 24.09万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-02 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7175452
• 关键词: Address; Affinity; Amino Acid Sequence; Antibodies; Architecture; Area; Aromatic Amino Acids; Attenuated; Avidin; Basic Science; Benchmarking; Benign; Binding; Biochemical; Biological; Biotechnology; Biotin; Breathing; Catalysis; Chemistry; Compatible; Complex; Coupling; Covalent Interaction; DNA; DNA Binding; DNA Sequence; Detection; Diagnostic; Drug Delivery Systems; Electrons; Electrostatics; Event; Foundations; Gene Expression; Generations; Genes; Genome; Hydrogen Bonding; Immobilization; Intercalating Agents; Ions; Laboratories; Lead; Learning; Libraries; Ligands; Marketing; Medical; Metals; Molecular; Naphthalene; Naphthalenes; Nature; Nucleic Acids; Organic Synthesis; Organic solvent product; Peptide Sequence Determination; Peptides; Phage Display; Phase; Principal Investigator; Proteins; Proteomics; Purpose; Range; Reaction; Recombinant Proteins; Research; Screening procedure; Signal Transduction; Solid; Solutions; Specificity; Stretching; Structure; Surface; System; Therapeutic; Therapeutic Intervention; Time; Vertebral column; Vision; Water; Work; aqueous; base; catalyst; covalent bond; design; design and construction; functional group; in vivo; molecular assembly/self assembly; next generation; novel; polypeptide; practical application; programs; protein aminoacid sequence; protein protein interaction; protein purification; protein structure; scaffold; sensor; size; tool; tryptophyltyrosine

DESCRIPTION (provided by applicant): But can we make it work in water? Chemists are now exploring the design of molecular architectures that extend beyond covalent bonding. Taking inspiration from Nature, molecules that fold or self-assemble are being designed from first principles. Creating molecular systems that fold and assemble in water is currently a major challenge, although once created, such systems will be able to interact with biological structures and molecules in unprecedented ways. Our early foldamer studies verified that aromatic donor-acceptor interactions can be used as a remarkably strong stabilizing interaction in water, producing folded, stacked structures (Lokey and Iverson, Nature, 1995, 375, 303-5.) called aedamers. More recently, we have made the exciting discovery that chains of electron rich aromatic units will specifically recognize a complementary chain of electron deficient aromatic units in aqueous solution to form a stable duplex (Gabriel and Iverson, J. of the Am. Chem. Soc., 2002, 124, 15174-15175.). The first two specific aims of this proposal describe the creation and characterization of novel folding and assembling molecular systems that in water exploit the stabilizing and recognition abilities of the electron rich 1,5-dialkoxynaphthalene (DAN) and the electron deficient 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) aromatic moieties. The last three specific aims take the next critical step and probe different interaction strategies with biological molecules. Spanning the range from basic science to practical application, we will 1) investigate an entirely new aedamer folding topology analogous to nucleic acid hairpins, 2) use the recognition ability of the DAN-NDI interaction to produce large molecular assemblies from smaller folding pieces, 3) investigate the utility of DAN-NDI interactions as a stabilizing force in a protein hydrophobic core, 4) create next-generation threading DNA poly-intercalators based on structures derived from NMR analysis of our NDI-based oligomers, and 5) use phage display to isolate a peptide with high affinity and specificity for binding a chain of NDI residues for potential use in biomedical and biotechnological applications.

描述（由申请人提供）：但是我们能让它在水中工作吗？化学家们现在正在探索超越共价键的分子结构的设计。从大自然中汲取灵感，折叠或自组装的分子正在从第一原理设计。创建在水中折叠和组装的分子系统目前是一个重大挑战，尽管一旦创建，这样的系统将能够以前所未有的方式与生物结构和分子相互作用。我们早期的折叠体研究证实，芳族供体-受体相互作用可用作水中非常强的稳定相互作用，产生折叠的堆叠结构（Lokey和Iverson，Nature，1995，375，303-5）。叫做爱达默斯最近，我们已经做出了令人兴奋的发现，即富电子芳族单元的链将特异性地识别水溶液中缺电子芳族单元的互补链以形成稳定的双链体（Gabriel和Iverson，J. of the Am.化学会，2002，124，15174-15175）。该提案的前两个具体目标描述了新型折叠和组装分子系统的创建和表征，该分子系统在水中利用富电子的1，5-二烷氧基萘（DAN）和缺电子的1，4，5，8-萘四羧酸二酰亚胺（NDI）芳族部分的稳定和识别能力。最后三个具体目标采取下一个关键步骤，并探索与生物分子的不同相互作用策略。 从基础科学到实际应用，我们将1）研究一种全新的类似于核酸发夹的aedamer折叠拓扑结构，2）利用DAN-NDI相互作用的识别能力从较小的折叠片段产生大分子组装体，3）研究DAN-NDI相互作用作为蛋白质疏水核心中的稳定力的效用，4）基于从我们的基于NDI的寡聚体的NMR分析得到的结构，创建下一代螺纹DNA多嵌插剂，和5）使用噬菌体展示来分离具有高亲和力和特异性的肽，用于结合NDI残基链，用于生物医学和生物技术应用中的潜在用途。