Development of a competitive binding assay for the Burkholderia cenocepacia lectin BC2L-A and structure activity relationship of natural and synthetic inhibitors
Burkholderia cenocepacia is an opportunistic Gram-negative pathogen and especially hazardous for cystic fibrosis patients. In analogy to its relative Pseudomonas aeruginosa , B. cenocepacia possess numerous lectins with roles in adhesion and biofilm formation. The LecB homolog BC2L-A is important fo...
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Published in | MedChemComm Vol. 7; no. 3; pp. 519 - 530 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
16.03.2016
|
Online Access | Get full text |
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Summary: | Burkholderia cenocepacia
is an opportunistic Gram-negative pathogen and especially hazardous for cystic fibrosis patients. In analogy to its relative
Pseudomonas aeruginosa
,
B. cenocepacia
possess numerous lectins with roles in adhesion and biofilm formation. The LecB homolog BC2L-A is important for biofilm structure and morphology. Inhibitors of this
d
-mannose specific C-type lectin could be useful as tools in
B. cenocepacia
biofilm research and potentially as anti-biofilm compounds against chronic infections. Here, we report the development of a fluorescence polarization-based competitive binding assay and its application in an extensive structure–activity relationship study of inhibitors of BC2L-A. In contrast to its homolog LecB, BC2L-A is highly selective for
d
-mannose-based ligands with an absolute requirement of its hydroxyl group at C6. A strict diastereoselectivity was observed for (6
S
)-mannoheptose-derived ligands. Intriguingly, bioisosteric substitution or methylation of hydroxyl groups directly involved in the calcium-coordination resulted in loss of inhibition for the two homologous lectins BC2L-A and LecB. |
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ISSN: | 2040-2503 2040-2511 |
DOI: | 10.1039/C5MD00557D |