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.
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
Eike-F
EF
Sachs
André
A
Nadler
Ulf
U
Diederichsen
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