| Autor: |
Christine, Cézard, Pascal, Sonnet, Benjamin, Bouvier |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 24(5) |
| ISSN: |
1432-1327 |
| Popis: |
Pyoverdines are Pseudomonas aeruginosa's primary siderophores. These molecules, composed of a fluorescent chromophore attached to a peptide chain of 6-14 amino acids, are synthesized by the bacterium to scavenge iron (essential to its survival and growth) from its environment. Hijacking the siderophore pathway to use pyoverdine-antibiotic compounds in a Trojan horse approach has shown promise but remains very challenging because of the synthetic efforts involved. Indeed, both possible approaches (grafting an antibiotic on pyoverdine harvested from Pseudomonas or designing a total synthesis route) are costly, time-consuming and low-yield tasks. Designing comparatively simple analogs featuring the salient properties of the original siderophore is thus crucial for the conception of novel antibiotics to fight bacterial resistance. In this work, we focus on the replacement of the pyoverdine chromophore, a major roadblock on the synthetic pathway. We propose three simpler analogs and evaluate their ability to complex iron and interact with the FpvA transporter using molecular modeling techniques. Based on these results, we discuss the role of the native chromophore's main features (polycyclicity, positive charge, flexibility) on pyoverdine's ability to bind iron and be recognized by membrane transporter FpvA and propose guidelines for the design of effective synthetic siderophores. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
