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[4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip‐Dependent and LpMip‐Independent Mechanisms

Deutscher, Robin C. E. ; Safa Karagöz, M. ; Purder, Patrick L. ; Kolos, Jürgen M. ; Meyners, Christian ; Oki Sugiarto, Wisely ; Krajczy, Patryk ; Tebbe, Frederike ; Geiger, Thomas M. ; Ünal, Can ; Hellmich, Ute A. ; Steinert, Michael ; Hausch, Felix (2024)
[4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip‐Dependent and LpMip‐Independent Mechanisms.
In: ChemBioChem, 2023, 24 (21)
doi: 10.26083/tuprints-00027244
Artikel, Zweitveröffentlichung, Verlagsversion

Es ist eine neuere Version dieses Eintrags verfügbar.

URL / URN: https://tuprints.ulb.tu-darmstadt.de/27244

Kurzbeschreibung (Abstract)

Legionella pneumophila is the causative agent of Legionnaires’ disease, a serious form of pneumonia. Its macrophage infectivity potentiator (Mip), a member of a highly conserved family of FK506‐binding proteins (FKBPs), plays a major role in the proliferation of the gram‐negative bacterium in host organisms. In this work, we test our library of >1000 FKBP‐focused ligands for inhibition of LpMip. The [4.3.1]‐bicyclic sulfonamide turned out as a highly preferred scaffold and provided the most potent LpMip inhibitors known so far. Selected compounds were non‐toxic to human cells, displayed antibacterial activity and block bacterial proliferation in cellular infection‐assays as well as infectivity in human lung tissue explants. The results confirm [4.3.1]‐bicyclic sulfonamides as anti‐legionellal agents, although their anti‐infective properties cannot be explained by inhibition of LpMip alone.

Typ des Eintrags:

Artikel

Erschienen:

2024

Autor(en):

Deutscher, Robin C. E. ; Safa Karagöz, M. ; Purder, Patrick L. ; Kolos, Jürgen M. ; Meyners, Christian ; Oki Sugiarto, Wisely ; Krajczy, Patryk ; Tebbe, Frederike ; Geiger, Thomas M. ; Ünal, Can ; Hellmich, Ute A. ; Steinert, Michael ; Hausch, Felix

Art des Eintrags:

Zweitveröffentlichung

Titel:

[4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip‐Dependent and LpMip‐Independent Mechanisms

Sprache:

Englisch

Publikationsjahr:

21 Mai 2024

Ort:

Darmstadt

Publikationsdatum der Erstveröffentlichung:

2 November 2023

Ort der Erstveröffentlichung:

Weinheim

Verlag:

Wiley-VCH

Titel der Zeitschrift, Zeitung oder Schriftenreihe:

ChemBioChem

Jahrgang/Volume einer Zeitschrift:

(Heft-)Nummer:

Kollation:

12 Seiten

DOI:

10.26083/tuprints-00027244

URL / URN:

https://tuprints.ulb.tu-darmstadt.de/27244

Zugehörige Links:

Herkunft:

Zweitveröffentlichung DeepGreen

Kurzbeschreibung (Abstract):

Alternatives oder übersetztes Abstract:

Alternatives Abstract	Sprache
In a screening of over 1000 FKBP-inhibitors [4.3.1]-bicyclic sulfonamides turned out to be the preferred binding scaffold for LpMip, a virulence factor of Legionella pneumophila. Although selected [4.3.1]-bicyclic sulfonamides showed anti-infective properties, LpMip was ruled out as sole target, with the results suggesting another FKBP is responsible for the observed effects.	Englisch

Freie Schlagworte:

Antiinfective, Legionella pneumophila, Inhibitors, Isomerases, Medicinal chemistry

ID-Nummer:

Artikel-ID: e202300442

Status:

Verlagsversion

URN:

urn:nbn:de:tuda-tuprints-272444

Zusätzliche Informationen:

A previous version of this manuscript has been deposited on a preprint server (https://doi.org/10.26434/chemrxiv-2023-vfssm).

Sachgruppe der Dewey Dezimalklassifikatin (DDC):

500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie