Shou Ming Du

New motifs in DNA nanotechnology

Recently, we have invested a great deal of effort to construct molecular building blocks from unusual DNA motifs. DNA is an extremely favorable construction medium. The sticky-ended association of DNA molecules occurs with high specificity, and it results in the formation of B-DNA, whose structure is well known. The use of stable-branched DNA molecules permits one to make stick-figures. We have used this strategy to construct a covalently closed DNA molecule whose helix axes have the connectivity of a cube, and a second molecule, whose helix axes have the connectivity of a truncated octahedron. In addition to branching topology, DNA also yields control of linking topology, because double helical half-turns of B-DNA or Z-DNA can be equated, respectively, with negative or positive crossings in topological objects. Consequently, we have been able to use DNA to make trefoil knots of both signs and figure of 8 knots. By making RNA knots, we have discovered the existence of an RNA topoisomerase. DNA-based topological control has also led to the construction of Borromean rings, which could be used in DNA-based computing applications. The key feature previously lacking in DNA construction has been a rigid molecule. We have discovered that DNA double crossover molecules can provide this capability. We have incorporated these components in DNA assemblies that use this rigidity to achieve control on the geometrical level, as well as on the topological level. Some of these involve double crossover molecules, and others involve double crossovers associated with geometrical figures, such as triangles and deltahedra.

Tight single-stranded DNA knots.

Trefoil (3(1)) and figure-8 (4(1)) knots have been synthesized from DNA molecules containing two single-turn helical domains, linked by four oligodeoxythymidine linkers. Both topologies are derived from the same DNA molecule. The tightest knots are fashioned by minimizing the lengths of the linkers. The shortest equal-length linkers from which a trefoil knot can be made readily are seven nucleotides long, in a 74-nucleotide molecule, whereas those in the shortest figure-8 knot are six nucleotides long, in a 70-nucleotide molecule. In addition to these limiting knots, other knots containing 80, 88, 96 and 104 nucleotides have been constructed. The mobilities of these molecules on denaturing gels show the conventional logarithmic dependence on length. Ferguson analysis of their mobilities indicates a linear dependence of surface area on length. The 80-mer trefoil knot is the tightest molecule that can be restricted in both domains.

Construction of DNA Polyhedra and Knots Through Symmetry Minimization

The goals of supramolecular chemistry include structural control on the nanometer scale comparable to that enjoyed by craft workers on the macroscopic scale.1 The ability to join, couple or weave two molecules together to produce a structure with the same certainty enjoyed by a carpenter, a plumber or a garment worker, would increase greatly the efficiency of materials scientists, chemists, and molecular biologists. Chemists have learned that it is not as simple to create structures from molecules as it is from macroscopic objects: They must rely on intrinsic propensities of precursors, because there are no nails, screws, or threads available to form bonds between atoms. Furthermore, the laws of physics do not permit all conceivable separations of atomic nuclei. In contrast, the components in biological systems often self-assemble spontaneously, by using complementary surfaces to form cohesive structures.