Synthesis and activity of p-azidobenzoyloxyferricrocin, a photoactivatableanalog of ferrichrome

p-azidobenzoyloxy desferriferricrocin (AF) 2, a photoactivatable analog of ferrichrome, was prepared by selective acylation of the serine group of fer ricrocin 1 in two steps: transesterification of ferricrocin followed by dem etallation. A model compound, (L) 2-benzyloxpcarbonylamino-3-p-azidobenzoyl oxy N-isopropyl propionamide 8, was separately synthesized in order to set up optimal transesterification conditions to avoid alpha, beta-elimination or epimerization of serine. Binding of iron-loaded AF (FeAF) to the FhuA ou ter membrane receptor protein of Escherichia coli AB2847 was demonstrated b y inhibition of ferrichrome transport, interference with the infection by t he bacteriophage phi 80 and with killing of cells by albomycin and colicin M. FeAF transported iron only weakly which indicates that the photoaffinity moiety is incompatible with transport or intracellular iron release from t he siderophore.