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

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.

Subject (DDC)

540 Chemistry

Keywords

Lectin, Pseudomonas aeruginosa, Inhibitor

Cite This

ISO 690

HOFMANN, Anna, Roman SOMMER, Dirk HAUCK, Julia STIFEL, Inigo GÖTTKER-SCHNETMANN, Alexander TITZ, 2015. Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa. In: Carbohydrate Research. 412, pp. 34-42. ISSN 0008-6215. eISSN 1873-426X. Available under: doi: 10.1016/j.carres.2015.04.010

BibTex

@article{Hofmann2015Synth-31849,
  year={2015},
  doi={10.1016/j.carres.2015.04.010},
  title={Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa},
  volume={412},
  issn={0008-6215},
  journal={Carbohydrate Research},
  pages={34--42},
  author={Hofmann, Anna and Sommer, Roman and Hauck, Dirk and Stifel, Julia and Göttker-Schnetmann, Inigo and Titz, Alexander}
}

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