The attachment of labels onto DNA is of utmost importance in many areas of biomedical research and is valuable in the construction of DNA-based functional nanomaterials. The copper(I)-catalyzed Huisgen cycloaddition of azides and alkynes (CuAAC) has recently been added to the repertoire of DNA labeling methods, thus allowing the virtually unlimited functionalization of both small synthetic oligonucleotides and large gene fragments with unprecedented efficiency. The CuAAC reaction yields the labeled polynucleotides in very high purity after a simple precipitation step. The reviewed technology is currently changing the way in which functionalized DNA strands are generated cost-efficiently in high quality for their application in molecular diagnostics systems and nanotechnological research.

Nitrile oxides react smoothly and rapidly with norbornene-modified DNA in a copper-free click reaction. The reaction allows high density functionalization of oligodeoxyribonucleotides (ODNs) with a large variety of molecules directly on solid supports and even in synthesizers without the need for an additional catalyst.

The outstanding self-recognition properties of DNA have been exploited in the use of this biomolecule as a template for the construction of nanoscale assemblies [1] and hybrid structures. [2,3] To further expand the utility of DNA for other applications, research is currently aimed at increasing its intrinsically low electric conductivity.[4] The selective coating of DNA with a thin layer of a conductive element, such as Ag, [5] Pd, [6] Pt, [7] Cu, [8] or Co, [9] has emerged as a promising avenue. Most coating procedures involve the reduction of electrostatically bound metal ions on the DNA by an exogeneous reductant to give small metal clusters attached to the DNA. In a second, development step, known from black-andwhite photography, these metal clusters function as nucleation sites for the reductive deposition of metal atoms until a continuous conductive coating is formed. Novel procedures aimed at increasing the selectivity of the metallization process are the decoration of DNA with functional groups to control the spatial distribution of the nucleation sites, [10] the photochemical deposition of silver on DNA strands, [11] and the formation of DNA-Pt II adducts as precursors for metal deposition on DNA.[12] The most critical step in the whole metallization process is the initial nucleation step. The uniformity and the distribution of the metal clusters define the homogeneity of the development step and hence the result of the metallization process. Unfortunately, nucleation in chemical reactions is still a poorly understood process and is therefore difficult to control.To coat DNA with silver, small silver clusters Ag n (n = 2, 4, 6…) that are able to undergo a development process need to be deposited on the DNA. These clusters can be formed in a redox reaction between Ag + in solution and aldehyde groups present on the DNA (Tollens reaction). Owing to the stoichiometry of the redox process, one aldehyde group can reduce two silver ions to form an Ag 2 cluster. Dialdehyde groups should be able to form an Ag 4 cluster (Scheme 1). It is suspected that these Ag 4 clusters, as a result of their electronic structure, are the smallest stable, developable (magic-size) silver clusters.[13] If this hypothesis is correct, the controlled formation of Ag 4 clusters on DNA should enable more reliable DNA metallization.To construct DNA with dialdehyde moieties, we functionalized DNA with cis-3,4-dihydroxypyrrolidine units, which Scheme 1. Transformation of diol-modified DNA-1 and DNA-3 into aldehyde-and dialdehyde-modified DNA-2 and DNA-4, followed by metallization steps.

Alkyne-bearing deazapurine triphosphates were prepared and successfully incorporated into DNA using the polymerase chain reaction (PCR). The obtained alkyne-labeled DNA was successfully used in a click reaction with galactose azide.

Die Markierung von DNA ist von größter Bedeutung für die Biomedizin und bildet die Basis für die Konstruktion DNA‐basierter funktionaler Nanomaterialien. Seit kurzem zählt die Kupfer(I)‐katalysierte Huisgen‐Cycloaddition von Aziden mit Alkinen (CuAAC) zum Repertoire der DNA‐Markierungsmethoden. Diese Methode ermöglicht die Modifizierung von DNA mit beispielloser Effizienz. Nicht nur kleine Oligonucleotide, sondern auch ganze Genfragmente können so hochgradig chemisch modifiziert werden. Die CuAAC‐Reaktion liefert die markierten Polynucleotide, meist nach einfacher Ausfällung, in ausgezeichneter Reinheit und ist auf dem besten Wege, die Synthese funktionalisierter DNA‐Stränge zu revolutionieren. Die Methode wird von entscheidender Bedeutung für die Erzeugung neuer diagnostischer Systeme und für die nanotechnologische Forschung sein.