Semisynthetic DNA-Protein Conjugates: Novel Tools in Molecular Nanotechnology

Christof M. Niemeyer

FB 2 - UFT, Biotechnology and Molecular Genetics, University of Bremen, Leobener St., D-28359 Bremen, Germany


A promising approach to the biomimetic bottom-up fabrication of nanometer-scaled devices is based on the utilization of biomolecular recognition systems, such as nucleic acid hybridization and protein-ligand interaction. We have developed conjugates of proteins and nucleic acids, synthesized by either covalent chemistry or self-assembling strategies. These systems can be utilized as novel tools in molecular biotechnology and nanotechnology. As an example, nanostructured supramolecular networks of streptavidin (STV) and double-stranded DNA have been studied by electrophoresis and scanning-force microscopy. These oligomeric DNA-protein conjugates can be utilized as reagents in Immuno-PCR, a highly sensitive method for the trace analysis of proteins and other antigens [1]. Another example concerns covalent conjugates of STV and single-stranded DNA oligomers [2]. These adducts are utilized as biomolecular adapters for the immobilization of biotinylated macromolecules on surfaces via nucleic acid hybridization. This method, termed DNA-directed immobilization (DDI), allows for the highly efficient, reversible and site-selective functionalization of solid supports with enzymes, immunoglobulins and other macromolecules. Thus, DDI is particularly suitable for the fabrication of laterally microstructured, reusable biochips and other sensor devices [3]. Moreover, covalent DNA-STV conjugates are also convenient for constructions on the nanometer-scale since they allow for selective positioning of biotin-derivatized molecules along a single-stranded nucleic acid carrier molecule. As an example, this approach allows to assemble gold nanoclusters and antibodies to form functional biometallic nanostructures, potentially useful as interface structures between electronic and biological systems [4].


[1] C. M. Niemeyer, M. Adler, B. Pignataro, S. Lenhert, S. Gao, L. F. Chi, H. Fuchs, and D. Blohm, Nucleic Acids Res. 27, 4553 (1999).

[2] C. M. Niemeyer, T. Sano, C. L. Smith, and C. R. Cantor, Nucleic Acids Res. 22, 5530 (1994).

[3] C. M. Niemeyer, L. Boldt, B. Ceyhan, and D. Blohm, Anal. Biochem. 268, 54 (1999).

[4] C. M. Niemeyer, W. Bürger, and J. Peplies, Angew. Chem. Int. Ed. 37, 2265 (1998).