English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Targeting the central pocket of the Pseudomonas aeruginosa lectin LecA

Siebs, E., Shanina, E., Kuhaudomlarp, S., da Silva Figueiredo Celestino Gomes, P., Fortin, C., Seeberger, P. H., et al. (2022). Targeting the central pocket of the Pseudomonas aeruginosa lectin LecA. Chembiochem, 23(3): e202100563. doi:10.1002/cbic.202100563.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
Article.pdf (Publisher version), 8MB
Name:
Article.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-

Locators

show

Creators

show
hide
 Creators:
Siebs, Eike, Author
Shanina, Elena1, Author              
Kuhaudomlarp, Sakonwan, Author
da Silva Figueiredo Celestino Gomes, Priscila, Author
Fortin, Cloé, Author
Seeberger, Peter H.2, Author              
Rognan, Didier, Author
Rademacher, Christoph1, Author              
Imberty, Anne, Author
Titz, Alexander, Author
Affiliations:
1Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863300              
2Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863306              

Content

show
hide
Free keywords: carbohydrates, glycoconjugates, glycomimetics, lectin, LecA
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2021-11-172022
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1002/cbic.202100563
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Chembiochem
  Other : Chembiochem
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Weinheim, Germany : Wiley-VCH
Pages: - Volume / Issue: 23 (3) Sequence Number: e202100563 Start / End Page: - Identifier: ISSN: 1439-4227