Dendritic DNA Building Blocks for Amplified Detection Assays and Biomaterials

摘要

Since the seminal work on the synthesis and characterization of dendritic molecules in the late 1970's, a variety of chemical dendrimers have been evolved for a number of applications in sensing and materials science.'11 Informed by advances in the synthesis of artificial deoxyribonucleic acid (DNA) oligonucleotides using solid-phase phosphoramidite chemistry, Horn and Urdea realized that this synthetic approach gives rise to the construction of fork- and comb-like DNA oligomers (1 and 2) that could be useful as basic building blocks for the assembly of DNA dendrimers by means of specific Watson-Crick base pairing. Indeed, their approach proved feasible and resulted in the development of commercial diagnostic tests for nucleic acids of pathogens, such as HIV (human immunodeficiency virus) and HCV (hepatitis C virus). At the same time, developments of dendritic DNA-based superstructures were initiated by the groundbreaking work of Seeman, who demonstrated that DNA crossover motifs, so-called three- and four-arm junctions (3 and 4, respectively), are accessible by self-assembly of designed oligonucleotides. When the junction motifs contain single-stranded overhangs ("sticky ends"), they can act as oligova-lent building blocks for the assembly of dendrimer-like superstructures that possess well-defined structural features on the nanometer length scale. This pioneering work has led to the establishment of the highly innovative and vibrant field of DNA nanotechnology, in which motifs such as 3 and 4, and especially more complex ones, are used extensively as building blocks for rationally designed two-dimensional nanoarrays, three-dimensional wire-frame objects, and even programmable dynamic systems with structure-directing properties. In addition to building blocks comprised of pure DNA, a variety of oligovalent DNA molecules containing chemical branch points have been introduced as components for DNA nanoconstruction. Representative examples include nickel cyclam (5) and porphyrin derivatives (6),branched phosphoramidites (7), trisoligonucleotides [13,14] tripodal oligonucleotide-functionalized modules (TOMs, 9), adenosine bis(phosphate) derivatives (e.g., 10), as well as other linkers for the generation of dendritic DNA structures.