Structure–Activity Relationship of Fluorinated Sialic Acid Inhibitors for Bacterial Sialylation
Sam J. Moons, Emiel Rossing, Jurriaan J. A. Heming, Mathilde A. C. H. Janssen, Monique van Scherpenzeel, Dirk J. Lefeber, Marien I. de Jonge, Jeroen D. Langereis, Thomas J. Boltje
Abstract
(NTHi) can evade the immune system by taking up and presenting host-derived sialic acids. Herein, we report a detailed structure-activity relationship of sialic acid-based inhibitors that prevent the transfer of host sialic acids to NTHi. We report the synthesis and biological evaluation of C-5, C-8, and C-9 derivatives of the parent compound 3-fluorosialic acid (SiaNFAc). Small modifications are tolerated at the C-5 and C-9 positions, while the C-8 position does not allow for modification. These structure-activity relationships define the chemical space available to develop selective bacterial sialylation inhibitors.