Enhancing Glycan Stability via Site-Selective Fluorination: Modulating Substrate Orientation by Molecular Design.

Single site OH to F substitution at the termini of maltotetraose leads to significantly improved hydrolytic stability towards alpha-amylase and alpha-glucosidase relative to the natural compound. Stability enhancements of around 1 order of magnitide result from these subtle point mutations. In both scenarios, modification of the monosaccharide furthest from the site of enzymatic cleavage leads to the greatest improvement in stability, and the configuration of the fluorine-bearing stereocenter has a clear impact on catalysis. This pre-clinical evaluation provides valuable guidelines for the development of tracer candidates for non-invasive bacterial imaging.