Interactions of calix[n]arenes with nucleic acids

Abstract

DNA interaction with artificial binders is of great interest, especially in light of the broad range of possible biomedical applications. The growing understanding of replication, transcription and translation opened the path for new approaches to target pathological effects at a very early stage. Meanwhile, the competitive binding to nucleic acids by designed molecules, which, for example, block certain sequences for natural binders, such as transcription factors, has become a promising concept in the context of gene therapy. On the other extreme, the transport of nucleic acids over the cell membrane into the nucleus by transfection agents opens the possibility to reprogram protein biosynthesis within host cells. In the past decades several substance classes have been developed for a noncovalent specific DNA binding with predictable biological effects, such as peptide nucleic acids or polyamide ligands. Calixarenes have not received so much attention, although they consist of a compact aromatic core tuneable in size, and allow the introduction of cationic functionalities at their upper and lower rims. Formerly being utilized as receptor moieties due to the possibility of complexating guests in their cavities, calixarenes are now also used as molecular scaffolds for multivalent ligands and are, therefore, suitable tools for cooperative DNA complexation. This review surveys specific supramolecular interactions between calixarene derivatives and nucleic acids, with an emphasis on structural elements in the calixarenes and the biological consequences of their complex formation with DNA strands.