Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa.

2.50
Hdl Handle:
http://hdl.handle.net/10033/556781
Title:
Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa.
Authors:
Hofmann, Anna; Sommer, Roman; Hauck, Dirk; Stifel, Julia; Göttker-Schnetmann, Inigo; Titz, Alexander
Abstract:
Biofilm formation and chronic infections with Pseudomonas aeruginosa depend on lectins produced by the bacterium. The bacterial C-type lectin LecB binds to the two monosaccharides l-fucose and d-mannose and conjugates thereof. Previously, d-mannose derivatives with amide and sulfonamide substituents at C6 were reported as potent inhibitors of the bacterial lectin LecB and LecB-mediated bacterial surface adhesion. Because d-mannose establishes a hydrogen bond via its 6-OH group with Ser23 of LecB in the crystal structure and may be beneficial for binding affinity, we extended d-mannose and synthesized mannoheptoses bearing the free 6-OH group as well as amido and sulfonamido-substituents at C7. Two series of diastereomeric mannoheptoses were synthesized and the stereochemistry was determined by X-ray crystallography. The potency of the mannoheptoses as LecB inhibitors was assessed in a competitive binding assay. The data reveal a diastereoselectivity of LecB for (6S)-mannoheptose derivatives with increased activity over methyl α-d-mannoside.
Affiliation:
hemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), D-66123 Saarbrücken, Germany.
Citation:
Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa. 2015, 412:34-42 Carbohydr. Res.
Journal:
Carbohydrate research
Issue Date:
5-May-2015
URI:
http://hdl.handle.net/10033/556781
DOI:
10.1016/j.carres.2015.04.010
PubMed ID:
26004349
Type:
Article
ISSN:
1873-426X
Appears in Collections:
publications of the junior research group chemical biology of carbohydrates ([HIPS]CBCH)

Full metadata record

DC FieldValue Language
dc.contributor.authorHofmann, Annaen
dc.contributor.authorSommer, Romanen
dc.contributor.authorHauck, Dirken
dc.contributor.authorStifel, Juliaen
dc.contributor.authorGöttker-Schnetmann, Inigoen
dc.contributor.authorTitz, Alexanderen
dc.date.accessioned2015-06-11T14:17:27Zen
dc.date.available2015-06-11T14:17:27Zen
dc.date.issued2015-05-05en
dc.identifier.citationSynthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa. 2015, 412:34-42 Carbohydr. Res.en
dc.identifier.issn1873-426Xen
dc.identifier.pmid26004349en
dc.identifier.doi10.1016/j.carres.2015.04.010en
dc.identifier.urihttp://hdl.handle.net/10033/556781en
dc.description.abstractBiofilm formation and chronic infections with Pseudomonas aeruginosa depend on lectins produced by the bacterium. The bacterial C-type lectin LecB binds to the two monosaccharides l-fucose and d-mannose and conjugates thereof. Previously, d-mannose derivatives with amide and sulfonamide substituents at C6 were reported as potent inhibitors of the bacterial lectin LecB and LecB-mediated bacterial surface adhesion. Because d-mannose establishes a hydrogen bond via its 6-OH group with Ser23 of LecB in the crystal structure and may be beneficial for binding affinity, we extended d-mannose and synthesized mannoheptoses bearing the free 6-OH group as well as amido and sulfonamido-substituents at C7. Two series of diastereomeric mannoheptoses were synthesized and the stereochemistry was determined by X-ray crystallography. The potency of the mannoheptoses as LecB inhibitors was assessed in a competitive binding assay. The data reveal a diastereoselectivity of LecB for (6S)-mannoheptose derivatives with increased activity over methyl α-d-mannoside.en
dc.languageENGen
dc.titleSynthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa.en
dc.typeArticleen
dc.contributor.departmenthemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), D-66123 Saarbrücken, Germany.en
dc.identifier.journalCarbohydrate researchen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.