Calix(4)aren-Dimere zur DNA-Erkennung in der grossen Furche

In this work, new Calix[4]arene dimers were developed, synthesized, and investigated for their DNA affinity. Anilincalix[4]arene dimers with aliphatic spacer units of varying lengths were created to examine the influence of spacer length on DNA affinity. Since side chains of basic amino acids in the recognition helix of many transcription factors can recognize base pairs in the major groove, a dimer with additional ammonium groups in the spacer and calixarenes with guanidinium groups at the upper rim were synthesized. Additionally, dimers with heterocyclic spacers were derived from the natural products Netropsin and Distamycin A, which bind to AT-rich DNA in the minor groove, providing additional contributions to DNA binding strength. The synthesized Calix[4]arene dimers were investigated for their DNA binding properties using fluorescence titrations with fluorescein-labeled DNA duplexes, ethidium bromide and DAPI displacement assays, thermal denaturation studies (UV-Vis melting curves), CD spectroscopy, NMR spectroscopy, and molecular modeling.