Structure-Activity Relationship of Fluorinated Sialic Acid Inhibitors for Bacterial Sialylation.

Published on May 27, 2021in Bioconjugate Chemistry4.031
· DOI :10.1021/ACS.BIOCONJCHEM.1C00194
Sam J. Moons6
Estimated H-index: 6
(Radboud University Nijmegen),
Emiel Rossing2
Estimated H-index: 2
(Radboud University Nijmegen)
+ 6 AuthorsThomas J. Boltje17
Estimated H-index: 17
(Radboud University Nijmegen)
Bacterial pathogens such as Nontypeable Haemophilus influenzae (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.
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