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 (2023)
[4.3.1]Bicyclic FKBP ligands inhibit Legionella Pneumophila infection by LpMip‐dependent and LpMip‐independent mechanisms.
In: ChemBioChem, 24 (21)
doi: 10.1002/cbic.202300442
Artikel, Bibliographie

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:	2023
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:	Bibliographie
Titel:	[4.3.1]Bicyclic FKBP ligands inhibit Legionella Pneumophila infection by LpMip‐dependent and LpMip‐independent mechanisms
Sprache:	Englisch
Publikationsjahr:	2 November 2023
Ort:	Weinheim
Verlag:	Wiley-VCH
Titel der Zeitschrift, Zeitung oder Schriftenreihe:	ChemBioChem
Jahrgang/Volume einer Zeitschrift:	24
(Heft-)Nummer:	21
Kollation:	12 Seiten
DOI:	10.1002/cbic.202300442
Zugehörige Links:	TUprints Zweitveröffentlichung Verwandtes Werk
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.
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
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
Fachbereich(e)/-gebiet(e):	Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut
Hinterlegungsdatum:	22 Mai 2024 06:07
Letzte Änderung:	22 Mai 2024 09:19
PPN:	518469859
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Verfügbare Versionen dieses Eintrags

• [4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip‐Dependent and LpMip‐Independent Mechanisms. (deposited 21 Mai 2024 13:52)
  • [4.3.1]Bicyclic FKBP ligands inhibit Legionella Pneumophila infection by LpMip‐dependent and LpMip‐independent mechanisms. (deposited 22 Mai 2024 06:07) [Gegenwärtig angezeigt]

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