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Under iron-deficient conditions most aerobic microorganisms secret low molecular-weight chelating compounds – siderophores, which actively transport ferric ions into the cells via specific transporters in the microbial membranes [1, 2]. The biomimetic approach allowed us to diversify the arsenal of siderophore-type molecules, introduce additional desired chemical and/or physical properties, and provide means to identify general motifs governing an interplay between structure and function in biological activity [1-5].
Taking into account, that siderophores are absent in the host cells, they are tempting targets for microbial imaging, for example with Ga-68 or Zr-89 using positron emission tomography (PET) [6]. Of the evaluated siderophores, 68Ga-ferrioxamine E and its close biomimetic analogues were shown as the most promising for possible applications in PET imaging of S. aureus and A. fumigatus species [7]. Currently we are working on other bacterial (P. aeruginosa) and fungal species, to better understand the in vivo speciation and differences in the biological recognition and uptake.
On the other hand, desferrioxamine B (DFO) is currently the most commonly used chelator to radiolabel biomolecules with 89Zr [6]. However, its in vivo stability has proven insufficient, and transchelation has been observed. Our Zr(IV) – DFO solution studies provided information on the actual chemical form of the complex in biological media [8], and this can contribute to a better understanding of the in vivo speciation and differences in the biological activity of this and other chelators [5-7].
Overall, mimics of siderophores hold potential as inert and stable carriers for Fe(III), Ga(III) and Zr(IV) ions for diagnostic medical applications. They also allow identifying critical microbial compartments in which siderophores accumulate and thus illuminate key targets for specific drugs against microbial diseases.
| References | [1] A. Szebesczyk, E. Olshvang, A. Shanzer, P.L. Carver, E. Gumienna-Kontecka, Coord. Chem. Rev., 2016, 84, 327. [2] A. Mular, K. Piasta, A. Jedyńczuk, K. Kamińska, E. Olshvang, N. Metzler-Nolte, E. Wojaczyńska, H. Kozłowski, E. Gumienna-Kontecka, Coord. Chem. Rev., 2024, 501, 215551/1. [3] E. Olshvang, A. Szebesczyk, H. Kozłowski, Y. Hadar, E. Gumienna-Kontecka, A. Shanzer, Dalton Trans. 2015, 44, 20850. [4] J. Besserglick, E. Olshvang, A. Szebesczyk, J. Englander, D. Levinson, Y. Hadar, E. Gumienna-Kontecka, A. Shanzer, Chem. Eur. J. 2017, 23, 13181. [5] Y. Toporivska, A. Mular, K. Piasta, M. Ostrowska, D. Illuminati, A. Baldi, V. Albanese, S. Pacifico, I.O. Fritsky, M. Remelli, R. Guerrini, E. Gumienna-Kontecka, Inorg. Chem. 2021, 60, 13332. [6] M. Petrik, Ch. Zhai, H. Haas, C. Decristoforo, Clin. Transl. Imaging, 2017, 5, 15. [7] A. Mular, A. Shanzer, H. Kozłowski, I. Hubmann, M. Misslinger, J. Krzywik, C. Decristoforo, E. Gumienna-Kontecka, Inorg. Chem. 2021, 60, 17846. [8]. Y. Toporivska, E. Gumienna-Kontecka, J. Iorg. Biochem., 198 (2019) 110753/1. |
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| Acknowledgement of financial support | The research has received funding from Polish National Science Centre (UMO-2017/26/A/ST5/00363 and UMO-2022/47/I/ST4/02354). |
