Triostin A derived hybrid for simultaneous DNA binding and metal coordination.
The natural product triostin A is known as an antibiotic based on specific DNA recognition. Structurally, a bicyclic depsipeptide backbone provides a well-defined scaffold preorganizing the recognition motifs for bisintercalation. Replacing the intercalating quinoxaline moieties of triostin A by nucleobases results in a potential major groove binder. The functionalization of this DNA binding triostin A analog with a metal binding ligand system is reported, thereby generating a hybrid molecule with DNA binding and metal coordinating capability. Transition metal ions can be placed in close proximity to dsDNA by means of non-covalent interactions. The synthesis of the nucleobase-modified triostin A analog is described containing a propargylglycine for later attachment of the ligand by click-chemistry. As ligand, two [1,4,7]triazacyclononane rings were bridged by a phenol. Formation of the proposed binuclear zinc complex was confirmed for the ligand and the triostin A analog/ligand construct by high-resolution mass spectrometry. The complex as well as the respective hybrid led to stabilization of dsDNA, thus implying that metal complexation and DNA binding are independent processes.
Sachs
Eike-F
EF
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
Nadler
André
A
Diederichsen
Ulf
U
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D057930:Click Chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper; D055029:Inverted Repeat Sequences; D011810:Quinoxalines / Q000737:chemistry; D044366:Transition Temperature; D015032:Zinc
D000900:Anti-Bacterial Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D011810:Quinoxalines; C031945:triostin A; D003300:Copper; D015032:Zinc