Matrix metalloproteinases (MMPs) are known to cause acne and periodontal disease and have been implicated in cancer through remodeling of the surrounding tissues to enable tumor growth. MMPs have an essential zinc(II) ion as part of the active site. Tetracycline and analogues are known to be effective treatments for acne and periodontal disease. One hypothesis involves the complexation of Zn(II) ions, thus reducing the availability of free Zn(II) in the extracellular environment for use by MMPs; tetracycline does not competitively inhibit MMPs with zinc already bound. The binding mode of tetracycline with metal ions has only been speculated.This exploratory work aims to test tetracycline and its coordination with Zn(II) ions. Titration methods show the stoichiometry of tetracycline to zinc in a biologically relevant, pH-controlled environment. Molecular modeling provides insight into tetracycline's coordination to Zn(II). By understanding tetracycline's binding mode, we can further the efficacy of this class of molecules.

Towards a rational design of a better tetracycline: Understanding zinc binding interactions in tetracycline

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.