title: Definitive structural assessment of enterococcal diheteroglycan.
abstract: Enterococcus faecalis is one of most important nosocomial and often multi-antibiotic resistant pathogens responsible for infections that are difficult to treat. Previously, a cell-wall polysaccharide termed diheteroglycan (DHG) was isolated and characterized as a promising vaccine candidate. However, the configuration of its lactic acid (LA) residue attached to the galactofuranoside unit was not assessed, although it influences conformation of DHG chain in terms of biological recognition and immune evasion. This study proves the R configuration of the LA residue by means of chemical analysis, investigation of intramolecular NMR nuclear Overhauser effects and molecular dynamics simulations of native DHG and corresponding R and S models, which were obtained by using pyranoside-into-furanoside rearrangement. As alternative treatment and prevention strategies for E. faecalis are desperately needed, this discovery may offer the prospect of a synthetic vaccine to actively immunize patients at risk.
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russian Federation).
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Krylov
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Gerbst
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Argunov
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Dmitrenok
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Shashkov
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Kaczynski
authors.forename: Johannes
authors.initials: J
authors.lastname: Huebner
authors.forename: Otto
authors.initials: O
authors.lastname: Holst
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
mesh_terms: D002473:Cell Wall / Q000737:chemistry*; D013293:Enterococcus faecalis / Q000737:chemistry*; D005697:Galactosides / Q000737:chemistry; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008968:Molecular Conformation; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D005697:Galactosides; D011134:Polysaccharides; D019344:Lactic Acid
keywords: carbohydrates; conformation analysis; furanoside; lactic acid; rearrangement