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Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Syntheses of Siderophore-Drug Conjugates Using a Convergent Thiol-Maleimide System
Raúl E Juárez-Hernández1, Patricia A Miller, Marvin J Miller
1Department of Chemistry and Biochemistry, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA.
Abstract:
Three siderophore-drug conjugates (sideromycins) were synthesized by preparation of a maleimide linked derivative of the siderophore desferrioxamine B and reacting the corresponding Ga(3+)-complex with freshly prepared thiol-containing antibiotics: loracarbef, ciprofloxacin and nadifloxacin. The conjugates and their synthetic precursors were tested against a broad panel of bacteria and were found to display Gram-positive selective, growth inhibitory activity (µM) indicating that this approach is suitable for the convergent synthesis and screening of novel sideromycins.
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