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单体构建块的制备，该构建块包含金属配体中心枢纽，连接四个或六个DNA序列。这些单体的自组装通过互补杂交产生超分子DNA纳米级或中尺度晶格。晶格从根本上不同于DNA树状大分子或其他DNA组装体，因为每个单体构建块在不止一个确定的位点上附着在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）晶格将与佐治亚理工学院的Loren Williams教授合作，用x射线衍射方法对其进行表征。表面结合的晶格将提供研究各种结合事件的机会。通过末端硫醇残基可以生成与金表面结合的单层或多层晶格。与波士顿大学的Rosina Georgiadis教授合作，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。通过适当共轭物的杂交，将有可能创建结合生物制剂以及非生物制剂（如荧光团、纳米粒子和量子点）的表面阵列。晶格的金属中心可以被看作是由晶格DNA臂的存在而有规则间隔的功能位点。为了研究这种金属阵列的特性，我们将制备基于多天线的光收集阵列来捕获光子，然后监测能量转移到中心卟啉或钌中心的过程。与Torsten Fiebig教授（波士顿学院）合作，我们将描述这些过程的中间体，寿命和效率。最后，规则的孔隙结构应该允许隔离或定时释放宏观药物或其他制剂。我们将表征孔隙结构，并确定这些材料对选定的大分子或纳米颗粒的多孔性