氟代唾液酸抑制剂的细菌唾液酸化结构-活性关系。

Cluster of Molecular Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen 6525 AJ, The Netherlands.

Translational Metabolic Laboratory, Department of Neurology, Donders Center for Brain Cognition and Behavior, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands.

Bioconjug Chem. 2021 Jun 16;32(6):1047-1051. doi: 10.1021/acs.bioconjchem.1c00194. Epub 2021 May 27.

Bacterial pathogens such as Nontypeable (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.

细菌病原体，如无特定型（NTHi），可以通过摄取和呈现宿主来源的唾液酸来逃避免疫系统。在此，我们报告了基于唾液酸的抑制剂的详细结构-活性关系，这些抑制剂可以阻止宿主唾液酸向 NTHi 的转移。我们报告了母体化合物 3-氟唾液酸（SiaNFAc）的 C-5、C-8 和 C-9 衍生物的合成和生物学评价。在 C-5 和 C-9 位置可以容忍小的修饰，而 C-8 位置不允许修饰。这些结构-活性关系定义了可用于开发选择性细菌唾液酸化抑制剂的化学空间。