Biomimetic siderophores

The physical and coordination chemistry of hydroxamate-based iron chelators, their thermodynamic, kinetic, structural, spectroscopic and surface properties, have been extensively reviewed Therefore, only selective aspects that are relevant for the design of biomimetic siderophore analogs will be discussed. 

The only clinically approved and therefore most studied natural siderophore is des-ferrioxamine B (DFO), and hence it serves as a reference compound in evaluating new biomimetic siderophores. The following discussion will include a short description of several natural hydroxamate siderophore families in separate tables, followed by the various attempts to prepare novel simplified structures that reproduce biological activity. These tables are not intended to cover the entire archive of known siderophores, but merely to allow the reader to observe structural variations, their chemical composition and location as well as conserved domains. 

The closely related structures show completely different microbial uptake characteristics. The 3D structures described above show distinct different orientation of the backbone amide (tangental in type 1 versus radial in type 2), which can be explained by the interactions that take place between the FhuA receptor and the ferrichrome siderophore -As mentioned, the second coordination sphere of natural ferrichrome in FhuA receptor is very sensitive to the distance and orientation between a proton donor and the proton acceptor, therefore the orientation of the amide groups in the biomimetic siderophore plays a crucial role in receptor recognition. 

A. Shanzer and J. Libman, Biomimetic Siderophores from Structural Probes to Diagnostic Tools, in hon Transport and Storage in Microorganisms, Plants, and Animals , Vol. 35 of Series Metal Ions in Biological Systems, eds. A. Sigel and... 

Biomimetic Siderophores From Stmctural Probes to Diagnostic Tools... 

---