Enterobactin on a Bead: Parallel, Solid Phase Siderophore Synthesis Reveals Structure-Activity Relationships for Iron Uptake in Bacteria.

A solid-phase platform for the precise and sequential synthesis of enterobactin analogues is described. This chemistry unites the power of solid-phase peptide synthesis with the unique opportunities and applications offered by siderophore chemistry. Here, a series of hybrid enterobactin hydroxamate/catecholate (HEHC) analogues were synthesized using both catechols and amino acid derived hydroxmate chelators. The HEHC analogues were evaluated for their ability to bind free iron and to promote growth in siderophore-auxotrophic mutant bacteria. We find that, in contrast to S. aureus or E. coli, a number of HEHC analogues promote growth in P. aeruginosa and structure-activity relationships (SARs) exist for the growth promotion via HEHC analogues in this organism.