Development of a competitive binding assay for the Burkholderia cenocepacia lectin BC2L-A and structure activity relationship of natural and synthetic inhibitors

Lade...
Vorschaubild
Dateien
Beshr_0-327635.pdf
Beshr_0-327635.pdfGröße: 418.34 KBDownloads: 432
Datum
2016
Autor:innen
Beshr, Ghamdan
Siebert, David Chan Bodin
Hofmann, Anna
Imberty, Anne
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
DOI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Hybrid
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
MedChemComm. 2016, 7(3), pp. 519-530. ISSN 2040-2503. eISSN 2040-2511. Available under: doi: 10.1039/c5md00557d
Zusammenfassung

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 (6S)-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.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690BESHR, Ghamdan, Roman SOMMER, Dirk HAUCK, David Chan Bodin SIEBERT, Anna HOFMANN, Anne IMBERTY, Alexander TITZ, 2016. Development of a competitive binding assay for the Burkholderia cenocepacia lectin BC2L-A and structure activity relationship of natural and synthetic inhibitors. In: MedChemComm. 2016, 7(3), pp. 519-530. ISSN 2040-2503. eISSN 2040-2511. Available under: doi: 10.1039/c5md00557d
BibTex
@article{Beshr2016Devel-33707,
  year={2016},
  doi={10.1039/c5md00557d},
  title={Development of a competitive binding assay for the Burkholderia cenocepacia lectin BC2L-A and structure activity relationship of natural and synthetic inhibitors},
  number={3},
  volume={7},
  issn={2040-2503},
  journal={MedChemComm},
  pages={519--530},
  author={Beshr, Ghamdan and Sommer, Roman and Hauck, Dirk and Siebert, David Chan Bodin and Hofmann, Anna and Imberty, Anne and Titz, Alexander}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/33707">
    <dc:creator>Titz, Alexander</dc:creator>
    <dcterms:abstract xml:lang="eng">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 (6S)-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.</dcterms:abstract>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-04-27T08:23:11Z</dcterms:available>
    <dc:creator>Siebert, David Chan Bodin</dc:creator>
    <dc:contributor>Siebert, David Chan Bodin</dc:contributor>
    <dc:creator>Hauck, Dirk</dc:creator>
    <dc:creator>Imberty, Anne</dc:creator>
    <dc:rights>terms-of-use</dc:rights>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:language>eng</dc:language>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/33707"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Titz, Alexander</dc:contributor>
    <dc:creator>Hofmann, Anna</dc:creator>
    <dc:contributor>Sommer, Roman</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/33707/1/Beshr_0-327635.pdf"/>
    <dc:contributor>Imberty, Anne</dc:contributor>
    <dc:contributor>Beshr, Ghamdan</dc:contributor>
    <dcterms:title>Development of a competitive binding assay for the Burkholderia cenocepacia lectin BC2L-A and structure activity relationship of natural and synthetic inhibitors</dcterms:title>
    <dcterms:issued>2016</dcterms:issued>
    <dc:creator>Beshr, Ghamdan</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-04-27T08:23:11Z</dc:date>
    <dc:contributor>Hofmann, Anna</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/33707/1/Beshr_0-327635.pdf"/>
    <dc:contributor>Hauck, Dirk</dc:contributor>
    <dc:creator>Sommer, Roman</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
PrĂĽfdatum der URL
PrĂĽfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Diese Publikation teilen