Self-assembly of DNA nanotubes and analysis of 2'-linked nucleic acids.

摘要

DNA is a valuable medium for controlling the structure of matter. Its promise lies in the addressability of its components via Watson-Crick base pairing, its robust structural nature, and the ability to program both structure and intermolecular interactions through sequence selection. Nevertheless, the most valuable uses of DNA in nanoconstruction are likely to include the use its architectural properties to control the spatial organization of components that are not nucleic acids.;DNA nanotubes are cylinder-like structures, which are useful as sheaths around rodlike species such as carbon nanotubes or biological systems. DNA six-helix nanotubes were successful assembled from two half-tubes through specifically designed lateral cohesive interactions. Since the inner cavity of six-helix bundle is similar to that of a double helix, we prototype a nanorod control by attaching a seventh DNA helix to the inside of a DNA six-helix bundle. Interior hydrophobic DNA six-helix nanotubes were constructed by methyl DNA inwhich anionic phosphate backbone was replaced with neutral methylphosphonate linkages. It will be useful for the sheathing of hydrophobic stuff. The intermolecular stacking interactions were observed by multi-domain (BTX) DNA motif. The formation of these tubes were demonstrated by gel electrophoresis and visualized by Atomic Force Microscopy (AFM).;My joint projects describe the thermodynamic analysis of 2'-modified nucleic acids. Nylon nucleic acid is a ladder polymer in which one rail is composed by a phosphodiester backbone and the other by a polyamide similar in structure to the polyamide nylon. Thermal denaturing studies revealed that the amide linkage significantly enhanced the binding affinity of nylon nucleic acids. The secondary structure of almost fully modified nylon nucleic acid was A-form. Besides 2'-modified uridine nucleotide, 2'-modified cytidine was developed. This is one step further toward the goal to control topology of industrial polymers by nucleic acids, as more bases will be necessary to be effective. 2'-Modified uridines containing long linkers (polyethylene glycol, PEG) were incorporated to DNA strand as interstrand crosslinking moieties. The covalent linkage through amide bond formation between the amino and carboxyl terminates could increase the binding affinity of DNA duplex, which may have important applications in antisense research.