Interaction of a Novel Iron Chelator with Model Membranes

Abstract

A novel fluorescent hexadentate iron chelator developed in our laboratory has been shown to inhibit the growth of Mycobacterium avium inside macrophages. Apart from its high affinity to iron, the compound seems to possess a key molecular structure to cross biological membranes, thus reaching the targets to deprive bacteria from iron.To get insight on the partition and location of this new compound, fluorescence spectroscopic studies are being performed in large unilamellar liposomes.To be able to separate liposome surface effects from lipophilicity, we measured the fluorescence anisotropy of two fluidity probes (DPH and TMA-DPH) in DMPC and DMPG liposomes prepared with the iron chelator. The results indicate that the primary interaction is near the lipid headgroup, with a partial molecular immersion in the outer leaflet, favouring negatively charged lipids.Our results suggest the importance of the first membrane penetration through the outer headgroups in the effectiveness of bacteriostatic agents with intra-cellular activity.Acknowledgements Partial financial support for this work was provided by “Fundacao para a Ciencia e Tecnologia” (FCT, Lisboa) through Project (PTDC/QUI/67915/2006); A.L thanks FCT for a PhD grant (SFRH/BD/30083/2006).View Large Image | View Hi-Res Image | Download PowerPoint Slide