Leveraging Stereoelectronic Effects in Biofilm Eradication: Synthetic β-Amino Human Milk Oligosaccharides Impede Microbial Adhesion As Observed by Scanning Electron Microscopy.

Abstract

Alongside Edward, Lemieux was among the earliest researchers studying negative hyperconjugation (i.e., the anomeric effect) or the preference for gauche conformations about the C1-O5 bond in carbohydrates. Lemieux also studied an esoteric, if not controversial, theory known as the reverse anomeric effect (RAE). This theory is used to rationalize scenarios where predicted anomeric stabilization does not occur. One such example is the Kochetkov amination where reducing end amines exist solely as the β-anomer. Herein, we provide a brief account of Lemieux's contributions to the field of stereoelectronics and apply this knowledge toward the synthesis of β-amino human milk oligosaccharides (βΑ-HMOs). These molecules were evaluated for their ability to inhibit growth and biofilm production in Group B Streptococcus (GBS) and Staphylococcus aureus. While the parent HMOs lacked antimicrobial and antibiofilm activity, their β-amino derivatives significantly inhibited biofilm formation in both species. Field emission gun-scanning single electron microscopy (FEG-SEM) revealed that treatment with β-amino HMOs significantly inhibits bacterial adherence and eliminates the ability of both microbes to form biofilms.