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Titel: Targeting the Central Pocket of the Pseudomonas aeruginosa Lectin LecA
VerfasserIn: Siebs, Eike
Shanina, Elena
Kuhaudomlarp, Sakonwan
da Silva Figueiredo Celestino Gomes, Priscila
Fortin, Cloé
Seeberger, Peter H.
Rognan, Didier
Rademacher, Christoph
Imberty, Anne
Titz, Alexander
Sprache: Englisch
Titel: ChemBioChem
Bandnummer: 23 (2022)
Heft: 3
Verlag/Plattform: Wiley
Erscheinungsjahr: 2021
Freie Schlagwörter: carbohydrates
glycoconjugates
glycomimetics
lectin
LecA
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate-binding proteins are central to the initial and later persistent infection processes, i. e. bacterial adhesion and biofilm formation. The biofilm matrix is a major resistance determinant and protects the bacteria against external threats such as the host immune system or antibiotic treatment. Therefore, the development of drugs against the P. aeruginosa biofilm is of particular interest to restore efficacy of antimicrobials. Carbohydrate-based inhibitors for LecA and LecB were previously shown to efficiently reduce biofilm formations. Here, we report a new approach for inhibiting LecA with synthetic molecules bridging the established carbohydrate-binding site and a central cavity located between two LecA protomers of the lectin tetramer. Inspired by in silico design, we synthesized various galactosidic LecA inhibitors with aromatic moieties targeting this central pocket. These compounds reached low micromolar affinities, validated in different biophysical assays. Finally, X-ray diffraction analysis revealed the interactions of this compound class with LecA. This new mode of action paves the way to a novel route towards inhibition of P. aeruginosa biofilms.
DOI der Erstveröffentlichung: 10.1002/cbic.202100563
URL der Erstveröffentlichung: https://doi.org/10.1002/cbic.202100563
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-392243
hdl:20.500.11880/35348
http://dx.doi.org/10.22028/D291-39224
ISSN: 1439-7633
1439-4227
Datum des Eintrags: 6-Mär-2023
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://chemistry-europe.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fcbic.202100563&file=cbic202100563-sup-0001-misc_information.pdf
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Chemie
Professur: NT - Univ.-Prof. Dr. phil. Alexander Titz
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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