Developing hybrid thiomaltodextrins as specific ligands to the maltodextrin transporter of Escherichia coli.

Maltodextrin transporters are bacteria specific and therefore have the potential to be targets of molecular vectors specific to bacteria. The maltodextrin binding protein (malE) of Escherichia coli (E. coli) binds to maltose and maltodextrins, and the reducing end of the substrate is important for functional binding to malE. We focus on E. coli and investigate the required conditions to bind malE of E. coli (ECmalE) and whether hybrid thiomaltodextrins that have maltose structure in the reducing end are transported by the maltodextrin transporter of E. coli. We used methyl-maltotrioside, methyl-thiomaltotrioside, and hybrid thiomaltodextrins, dithiomaltotetraose, trithiomaltopentaose, 6″-fluoro-dithiomaltotetraose, and 6″-fluoro-trithiomaltopentaose. The affinities of sugars to ECmalE and maltodextrin binding protein of Staphylococcus aureus (SAmalE) were evaluated with isothermal titration calorimetry (ITC). Although the effect of O-methyl derivatization of the anomeric carbon was limited on binding to EC and SAmalEs, thio-glycosyl bonds inhibited conformational change of ECmalE which is required for binding to the malFGK2 complex and binding to SAmalE. Hybrid thiomaltodextrins bound with ECmalE with conformational change but not with SAmaE. The maltodextrin transporter of E. coli reconstructed in nanodisks reacted with hybrid thiomaltodextrins in vitro. Hybrid thiomaltodextrins showed limited potential as carbon sources, but they increased the growth of E. coli induced by maltodextrins. Our results suggest that introducing the maltose structure on the reducing end and a glucose molecule on the non-reducing end might make non-ligand sugar analogs specific ligands for the maltodextrin transporter of E. coli. Based on our findings, further studies may investigate the potential of hybrid thiomaltodextrins as specific vectors targeting Enterobacteriaceae.