Abstract
Siderophores are low molecular weight ferric ion chelators synthesized by bacteria in iron limiting conditions. These chelators scavenge iron and are recognized in their ferric-bound state by highly conserved surface receptors which promote ATP dependent internalization after which the metal center can be liberated by reduction or fragmentation of the siderophore scaffold. This dissertation sought to answer two primary questions: 1) can rationally designed inhibitors elucidate the mechanism of siderophore biosynthesis by the iterative siderophore synthetase DesD and 2) can the receptor/transporter complexes present in pathogenic bacteria be exploited for targeted imaging of bacterial infection by a radiolabeled siderophore-antibiotic conjugate? Herein, the synthesis of tight binding inhibitors for DesD which mimic the reactive intermediates in the catalytic cycle are reported with crystal structures identifying novel substrate binding modes. A heterobifunctional imaging agent of bacterial infection was also designed and validated in vivo.
Committee Chair
Timothy Wencewicz
Degree
Doctor of Philosophy (PhD)
Author's Department
Chemistry
Document Type
Dissertation
Date of Award
6-5-2026
Language
English (en)
DOI
https://doi.org/10.7936/sshy-qd11
Recommended Citation
Merrick, Collin Earl, "Synthetic Siderophores as Biological Probes and Medical Imaging Agents" (2026). Arts & Sciences Graduate Student Theses and Dissertations. 3840.
The definitive version is available at https://doi.org/10.7936/sshy-qd11