The ribosome builds proteins by joining together amino acids in an order determined by messenger RNA. Here, we report on the design, synthesis, and operation of an artificial small-molecule machine that travels along a molecular strand, picking up amino acids that block its path, to synthesize a peptide in a sequence-specific manner. The chemical structure is based on a rotaxane, a molecular ring threaded onto a molecular axle. The ring carries a thiolate group that iteratively removes amino acids in order from the strand and transfers them to a peptide-elongation site through native chemical ligation. The synthesis is demonstrated with ~10(18) molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry.

[reaction: see text] We report the development of the Cu(I)-catalyzed Huisgen cycloaddition (click) reaction for the multiple postsynthetic labeling of alkyne-modified DNA. A series of alkyne-modified oligodeoxyribonucleotides (ODNs) of increasing alkyne density were prepared, and the click reaction using various azide labels was investigated. Complete high-density conversion was observed for ODNs containing up to six consecutive alkyne functions. Compatibility of the click conditions with long DNA strands was shown using a PCR product obtained with an alkyne-modified primer.

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.

One, two, or three: An efficient, modular, and robust protocol has been developed for the multiple functionalization of DNA. It is based on the click reaction of azides with the alkyne substituents on an oligodeoxyribonucleotide (ODN), which was prepared by the standard phosphoramidite method (see scheme). ODNs can thus be labeled with two sensitive molecules, and even triple modification is possible.

Letting off steam: A temperature‐controlled valve system permits the targeted release of guest fluorescein molecules from the pores of colloidal mesoporous silica particles. The pore‐opening temperature is dependent on the length of double‐stranded DNA linkers. Avidin proteins that are joined to the DNA by a biotin modification act as the molecular valve at the exits to the pores.