Synthesis of β-arabinofuranoside glycolipids, studies of their binding to surfactant protein-A and effect on sliding motilities of M. smegmatis

Abstract

Surfactant protein A (SP-A), which is a lung innate immune system component, is known to bind glycolipids present at the cell surface of a mycobacterial pathogen. Lipoarabinomannan (LAM), a component of mycobacterial thick, waxy cell wall, is one of the glycolipid ligands for SP-A. In order to assess binding of synthetic glycolipids with SP-A and the glycosidic linkage preferences for the interaction, β-arabinofuranoside trisaccharide glycolipids constituted with β-(1→2), β-(1→3) and β-(1→2), β-(1→5) linkages relevant to LAM were synthesized through chemical glycosylations. The efficacies of synthetic glycolipids to interact with SP-A were assessed by using the surface plasmon resonance (SPR) technique, from which association-dissociation rate constants and equilibrium binding constants were derived. The equilibrium binding constants of the interaction of two constitutionally varying β-arabinofuranoside glycolipids with SP-A were found to be in the millimolar range. A comparison of the results with few α-anomeric arabinofuranoside glycolipids showed that glycolipids with β-anomeric linkages were having relatively lower equilibrium binding constants than those with α-anomeric linkages in binding to the protein, whereas oligosaccharides alone, without lipidic chains, exhibited higher equilibrium binding constants. Further, the synthetic compounds inhibited the growth of mycobacteria and affected sliding motilities of the bacteria, although to an extent relatively lesser than that of synthetic compounds constituted with α-anomeric linkages.

Mannopyranoside Glycolipids Inhibit Mycobacterial and Biofilm Growth and Potentiate Isoniazid Inhibition Activities in M. smegmatis

“…The glycolipids are composed of lipidic and mannan portions, which qualitatively follow the pattern of components present in mycobacterial cell wall bound lipomannans. Our earlier studies on a series of synthetic oligoarabinan and oligoarabinomannan glycolipids demonstrated a reduction in mycobacterial growth upon treatment with these glycolipids . A pertinent query in these studies is the role of glycolipids composed of individual sugar moieties, as opposed to mixed oligoarabinomannan glycolipids.…”

“…Whereas oligoarabinomannan glycolipids show potent mycobacterial inhibitory activities in growth and biofilm phases, studies on oligoarabinan‐containing glycolipids show weaker inhibitory effects on growth phases and biofilm formation of M . smegmatis . We also recently identified that synthetic glycolipids supplemented the inhibition activities of the drug isoniazid on biofilm‐grown mycobacterium; thus suggesting the role of glycolipids on the drug involved in the inhibition of cell wall biosynthesis .…”

“…From a series of studies, we previously identified that synthetic arabinomannan‐containing glycolipids exhibited potent inhibitory effects against M. smegmatis in its growth and biofilm phases. A strong inhibitory effect against mycobacterial sliding motility was also observed . Further chromatographic and mass spectroscopic analysis of the lipid profile suggested a regulatory effect in the presence of glycolipids .…”

The role of ω‐subunit of Escherichia coli RNA polymerase in stress response

“…Biofilm quantification was carried out in three biological replicates. A parallel experiment was carried out in which OD 600 of all the strains was monitored to measure the cell culture density (Naresh et al., ; Syal, ).…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

“…As fouling-resistant SAMs: Synthesis, monolayer properties, and antifouling behavior (Fyrner et al, 2011) Sucrose monolaurate TOF Synthesis from sucrose and vinyl laurate by action of alkaline protease from Bacillus licheniformis (Laurino et al, 2011) 3-Thioglycosylated 5,6-diacetoxyindole derivatives TOF Thioglycosylation using a selenium-based dynamic-mixture method (Adinolfi et al, 2012) Glycolipids Arabinofuranoside-containing glycolipids TOF Synthesis and interaction with surfactant protein A (Naresh et al, 2011) Arabinofuranoside-containing glycolipids TOF Synthesis and binding to surfactant protein A and effect on sliding motilities of M. smegmatis (Naresh et al, 2012) Cholesteryl-6-Otetradecanoyl--Dglucopyranoside MALDI Chemoenzymatic synthesis 4…”