title: 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.
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Kottari
authors.initials: K
authors.lastname: Naresh
authors.forename: Prakash Gouda
authors.initials: PG
authors.lastname: Avaji
authors.forename: Krishnagopal
authors.initials: K
authors.lastname: Maiti
authors.forename: Binod K
authors.initials: BK
authors.lastname: Bharati
authors.forename: Kirtimaan
authors.initials: K
authors.lastname: Syal
authors.forename: Dipankar
authors.initials: D
authors.lastname: Chatterji
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Jayaraman
mesh_terms: D001089:Arabinose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006017:Glycolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000737:chemistry; D008124:Locomotion / Q000187:drug effects; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000276:immunology*; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology*; D013237:Stereoisomerism; D020349:Surface Plasmon Resonance; D014312:Trisaccharides / Q000378:metabolism / Q000494:pharmacology
chemical_list: D006017:Glycolipids; D008070:Lipopolysaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D014312:Trisaccharides; C431714:arabinofuranose; C050016:lipoarabinomannan; D001089:Arabinose