Siderophore Structure

The identity of the hard donor group and how it is incorporated in a molecular structure has a bearing on the affinity of a siderophore for iron(III). An analysis of siderophore structure and its relationship to iron(III) binding affinity as expressed by the thermodynamic stability constant is useful in understanding structure/function relationships and in the design of siderophore mimics for specific applications. 

There are a variety of factors concerning siderophore architecture that can contribute to the stability of iron-siderophore complexes. The overall architecture for natural multidentate siderophores can be any one of a number of different types linear, 

Another factor that relates complex stability and siderophore architecture is the chelate effect. The chelate effect is represented by an increase in complex stability for a multidentate ligand when compared to complexes with homologous donor atoms of lower denticity. The effect can be observed when comparing the stability of complexes of mono-hydroxamate ligands to their tris-hydroxamate analogs, such as ferrichrome (6) or desferrioxamine B (4). However, the increase in stability alone is not sufficient to explain the preponderance of hexadentate siderophores over tetradentate or bidentate siderophores in nature, and the chelate effect is not observed to a great extent in some siderophore structures (10,22,50,51). 

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As mentioned previously, siderophores must selectively bind iron tightly in order to solubilize the metal ion and prevent hydrolysis, as well as effectively compete with other chelators in the system. The following discussion will address in more detail the effect of siderophore structure on the thermodynamics of iron binding, as well as different methods for measuring and comparing iron-siderophore complex stability. The redox potentials of the ferri-siderophore complexes will also be addressed, as ferri-siderophore reduction may be important in the iron uptake process in biological systems. 

Neilands, J. B. (1995). Siderophores structure and function of microbial iron transport compounds, J. Biol. Chem., 270, 26 723-26 726. 

Demange P, Bateman A, Mertz C, Dell A, Piemont Y, Abdallah MA (1990) Bacterial Siderophores Structure of Pyoverdins Pt, Siderophores of Pseudomonas tolaasii NCPPB 2192, and Pyoverdins Pf, Siderophores of Pseudomonas fluorescens CCM 2798. Identification of an Unusual Natural Amino Acid. Biochemistry 29 11041... 

Demange P, Wendenbaum S, Bateman A, Dell A, Meyer JM, Abdallah MA (1986) Bacterial Siderophores Structure of Pyoverdins and Related Compounds. In Swinburne TR (ed) Iron, Siderophores, and Plant Diseases. Plenum, New York, p 131... 

Demange P, Wendenbaum S, Linget C, Bateman A, MacLeod J, Dell A, Albrecht AM, Abdallah MA (1989) Pseudomonas Siderophores Structure and Physicochemical Properties of Pyoverdins and Related Peptides. Second Forum on Peptides 174 95... 

Renshaw JC, Robson GD, Trinci API, Wiebe MG, Livens FR, Coiiison D, Taylor RJ (2002) Fungal Siderophores Structures, Functions and Application. Mycoi Res 106 1123... 

Wong-Lun-Sang S, Bemardini JJ, Hennard C, Kyslik P, Dell A, Abdallah MA (1996) Bacterial Siderophores Structure Elucidation, 2D H and C NMR Assignments of Pyoverdins Produced by Pseudomonas floorescens CHAO. Tetrahedron Lett 37 3329... 

Some natural antibiotics contain a siderophore structure, for instance, 5i-albomycin 35, which is produced by Streptomyces subtropicus. The linear tripeptide portion chelates Fe(III) and, thereby, is able to utilize the iron-transport system of a range of microorganisms. Subsequent to uptake, peptidases localized in the cytoplasmic membrane hydrolytically release the toxic thioribosyl moiety. In principle, this property can be used for selective drug delivery. Preliminary studies indicated that substantial modification of the siderophore framework can be tolerated by microbial iron-transport systems. Surprisingly, simple modifications can be made to cephalosporin molecules, which endow them with the ability to interact with microorganism iron-transport mechanisms. Thus, simple incorporation of a catechol moiety, as in 36, endows this molecule with enhanced activity against Pseudomonas aeruginosa when compared... 

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