DNA Lattices for the Study of Biological Processes

用于生物过程研究的 DNA 晶格

• 批准号: 7098298
• 负责人: LARRY W MCLAUGHLIN
• 金额: $ 26.98万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7098298
• 关键词: X ray crystallography; biotechnology; chemical models; chemical structure function; combinatorial chemistry; crystallization; drug discovery /isolation; intermolecular interaction; ligands; metal complex; model design /development; molecular assembly /self assembly; molecular dynamics; monomer; nanotechnology; nucleic acid chemical synthesis; nucleic acid repetitive sequence; peptide chemical synthesis; platinum; surface plasmon resonance; thiols

DESCRIPTION (provided by applicant): This project will involve the preparation of DNA monomer building blocks that contain metal-ligand central hubs tethering either four or six DNA sequences. Self-assembly of these monomers by complementary hybridization generates supramolecular DNA nanoscale or mesoscale lattices. Lattices differ fundamentally from DNA dendrimers or other DNA assemblies since each monomer building block attaches to the growing supramolecular structure at more than one defined site. The result of lattice assembly is a regular array of DNA sequences, similar to a macroscopic crystal. Both tetrahedral (diamond) and octahedral (cubic) lattices will be characterized by x-ray diffraction methods in collaboration with Prof. Loren Williams (Georgia Tech). Surface-bound lattices will provide the opportunity to study a variety of binding events. Monolayers or multiple layers of the lattice can be generated bound to a gold surface through terminal thiol residues. In collaboration with Prof. Rosina Georgiadis (Boston University), we will be able to study the rates and extents of monolayer formation, as well as the rates and extents of ligand or protein binding to the surface-bound lattices. Through hybridization of appropriate conjugates, it will be possible to create surface arrays of bound biologicals as well as non-biologicals such as fluorophores, nanoparticles and quantum dots. The metal centers of the lattices can be viewed as functional sites that are spaced regularly by the presence of the DNA arms of the lattice. To study the properties of such metal arrays we will prepare light harvesting arrays based upon multiple antennae to capture photons and then monitor the energy transfer process to a central porphyrin or ruthenium center. In collaboration with Prof. Torsten Fiebig (Boston College) we will characterize the intermediates, lifetimes and efficiencies of these processes. Finally, the regular pore structure should permit the sequestering or the timed release of macroscale Pharmaceuticals or other agents. We will characterize the pore structure and determine how porous these materials are to selected macromolecules or nanoparticles

描述（由申请人提供）：该项目将涉及 DNA 单体构件的制备，其中包含连接四个或六个 DNA 序列的金属配体中心枢纽。这些单体通过互补杂交进行自组装，生成超分子 DNA 纳米级或介观级晶格。晶格与 DNA 树枝状聚合物或其他 DNA 组装体有根本的不同，因为每个单体构建块在多个定义的位点附着到不断生长的超分子结构上。晶格组装的结果是DNA序列的规则阵列，类似于宏观晶体。四面体（菱形）和八面体（立方体）晶格都将与 Loren Williams 教授（佐治亚理工学院）合作，通过 X 射线衍射方法进行表征。表面结合晶格将为研究各种结合事件提供机会。可以通过末端硫醇残基与金表面结合生成单层或多层晶格。通过与 Rosina Georgiadis 教授（波士顿大学）合作，我们将能够研究单层形成的速率和程度，以及配体或蛋白质与表面结合晶格结合的速率和程度。通过适当缀合物的杂交，将有可能创建结合的生物制品以及非生物制品（例如荧光团、纳米颗粒和量子点）的表面阵列。晶格的金属中心可以被视为功能位点，这些位点因晶格 DNA 臂的存在而规则地间隔开。为了研究这种金属阵列的特性，我们将准备基于多个天线的光捕获阵列来捕获光子，然后监测到中心卟啉或钌中心的能量转移过程。我们将与 Torsten Fiebig 教授（波士顿学院）合作，描述这些过程的中间体、寿命和效率。最后，规则的孔隙结构应允许隔离或定时释放大尺度药物或其他药剂。我们将表征孔结构并确定这些材料对选定的大分子或纳米颗粒的多孔程度