Discovery of Orally Bioavailable FmlH Lectin Antagonists as Treatment for Urinary Tract Infections.

ABSTRACT: FmlH, a bacterial adhesin of uropathogenic Escherichia coli (UPEC), has been shown to provide a fitness advantage in colonizing the bladder during chronic urinary tract infections (UTIs). Previously reported ortho-biphenyl glycosides based on βGal and βGalNAc have excellent binding affinity to FmlH and potently block binding to its natural carbohydrate receptor, but they lack oral bioavailability. In this paper, we outline studies where we have optimized compounds for improved pharmacokinetics, leading to the discovery of novel analogues with good oral bioavailability. We synthesized galactosides with the anomeric O-linker replaced with more stable S- and C-linked linkers. We also investigated modifications to the GalNAc sugar and modifications to the biphenyl aglycone. We id

SUBMITTER: Maddirala AR 

PROVIDER: S-EPMC10994195 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature