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research

Branched DNA Structures

Biological and nanotechnological applications

Design: Because they can bind to specific DNA sequences, branched DNA structures are an important synthetic target, and are starting to be used for diagnostic applications (e.g., HIV detection). We have been interested in generating branched DNA structures with a transition metal at their branch point (1).
Transition metal complexes can be luminescent or redox active, and thus complex 1 can act as a "chemical spy", a molecule which can signal biological events, such as the presence of a specific DNA sequence. This is a very useful feature in the field of genomics in general, and particularly for the rapid identification of genes associated with disease.



Biological Properties: In addition to their potential importance as biosensors, complexes like 1 can act as building blocks to generate higher-order DNA structures, such as the two structures shown below. These can be formed by the self-assembly of complex 1 with two complementary DNA strands. There has been increasing interest recently in the generation of higher-order structures of nucleic acids. From the biological standpoint, these branched structures can mimic, and thus provide valuable information on similar naturally occuring structures, such as those involved in replication, gene recombination and repair, and selective gene repression mechanisms.


Applications in Nanotechnology: The other important motivation for generating higher-order DNA structures comes from the field of nanotechnology. This very exciting field seeks to control and arrange matter at the nanometer (10-9 m) scale, in order to make extremely small molecule-based devices and machines. Not only will this field result in making very high-performance materials in fields as diverse as electronics and medicine, but nanotechnology promises to revolutionalize the way we look at chemical matter. This is because the properties of materials at the nanometer scale are very different from either the properties of individual molecules, or those of the bulk material.
DNA is in fact one of the most promising building blocks for the construction of nanoscale materials. This "smart" molecule can select its complementary partner from a "soup" of hundreds of other DNA molecules, which is unique for a molecule. This allows the use of DNA as a very well-defined template to arrange complex patterns on the nanomatric scale. Our branched DNA complexes represent a useful building block and a simple method to generate DNA-based nanoscale materials, and we are currently actively exploring their self-assembly properties.

This project provides experience in the synthesis of small molecules and DNA analogues, in DNA structure and dynamics, and in molecular modeling.

D. Mitra, N. Di Cesare, H. F. Sleiman*; "Self-Assembly of Cyclic Metal-DNA Nanostructures Using Ruthenium Bipyridine Branched Oligonucleotides", Angew. Chem. Int. Ed. Engl., 2004, 43, 5804-5808. (Communication), pdf

I. Vargas-Baca, D. Mitra, H. Zulyniak, J. Banerjee, H. F. Sleiman*; "Solid-Phase Synthesis of Transition Metal-Linked Branched Oligonucleotides", Angew. Chem. Int. Ed. Engl., 2001, 40, 4629-4632. (Communication), pdf