Toward Dual-Target Glycomimetics against Two Bacterial Lectins to Fight Pseudomonas aeruginosa–Burkholderia cenocepacia Infections: A Biophysical Study DOI Creative Commons
Giulia Antonini,

Mario Fares,

Dirk Hauck

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Chronic lung infections caused by Pseudomonas aeruginosa and Burkholderia cenocepacia pose a severe threat to immunocompromised patients, particularly those with cystic fibrosis. These pathogens often infect the respiratory tract, available treatments are limited due antibiotic resistance. Targeting bacterial lectins involved in biofilm formation host-pathogen interactions represents promising therapeutic strategy. In this study, we evaluate potential of synthetic fucosylamides as inhibitors two LecB (P. aeruginosa) BC2L-C-Nt (B. cenocepacia). Using suite biophysical assays, assessed their binding affinities, identifying three β-fucosylamides dual-target ligands, while crystallography studies revealed atomic basis these ligands interact both lectins. The emerged classes compounds represent solid starting point for necessary hit-to-lead optimization future dual aiming at treatment coinfections pathogens.

Язык: Английский

Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens DOI Creative Commons
Deepanshi Saxena, Rahul Maitra,

Rakhi Bormon

и другие.

npj Antimicrobials and Resistance, Год журнала: 2023, Номер 1(1)

Опубликована: Дек. 20, 2023

Emerging resistance to all available antibiotics highlights the need develop new with novel mechanisms of action. Most currently used target Gram-positive bacteria while Gram-negative easily bypass action most drug molecules because their unique outer membrane. This additional layer acts as a potent barrier restricting entry compounds into cell. In this scenario, several approaches have been elucidated increase accumulation bacteria. review includes brief description physicochemical properties that can aid enter and accumulate in covers different strategies or membrane-mediated bacterial pathogens.

Язык: Английский

Процитировано

63
A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C DOI Creative Commons
Christina Jordan, Kathrin Siebold, Patricia Priegue

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(22), С. 15366 - 15375

Опубликована: Май 20, 2024

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating importance fluorine drug discovery, this molecular editing approach serves multitude purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation disialoside with two carrier proteins (CRM197 and PorA) enabled semisynthetic be generated; was then investigated six groups mice. The individual levels antibodies formed were compared classified highly glycan-specific protective. All glycoconjugates induced stable long-term IgG response binding native CPS epitope achieved. generated protective MenC MenB; vitro SBA OPKA assays. By merging glycan an outer cell membrane protein MenB, bivalent both created. It is envisaged that validation synthetic, bioisostere potent antigen will open new therapeutic avenues.

Язык: Английский

Процитировано

11
Multiple bacteria recognition mechanisms and their applications DOI

Xuechi Yin,

Jinrui Shan,

Leina Dou

и другие.

Coordination Chemistry Reviews, Год журнала: 2024, Номер 517, С. 216025 - 216025

Опубликована: Июнь 18, 2024

Язык: Английский

Процитировано

9
Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis DOI Creative Commons
Elisa Pérez-Moreno, Claudia Oyanadel, Adely de la Peña

и другие.

Biological Research, Год журнала: 2024, Номер 57(1)

Опубликована: Апрель 4, 2024

Abstract Galectins are soluble glycan-binding proteins that interact with a wide range of glycoproteins and glycolipids modulate broad spectrum physiological pathological processes. The expression subcellular localization different galectins vary among tissues cell types change during processes tissue repair, fibrosis cancer where epithelial cells loss differentiation while acquiring migratory mesenchymal phenotypes. epithelial-mesenchymal transition (EMT) occurs in the context these can include modifications glycosylation patterns affecting their interactions galectins. Moreover, overexpression certain has been involved development outcomes EMT. This review focuses on roles mechanisms Galectin-1 (Gal-1), Gal-3, Gal-4, Gal-7 Gal-8, which have physiologic pathogenic EMT contexts.

Язык: Английский

Процитировано

8
Stereoselective Synthesis of 1,2‐cis‐α‐Glycosyl Thiols and Trehalose‐Type α,α’‐Thiodisaccharides by Cryo Thiol‐Ene Photocoupling – Thio‐Click Reaction in Frozen State DOI Creative Commons

Viktor Kelemen,

Miklós Bege,

Nóra Debreczeni

и другие.

Chemistry - A European Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract α‐Glycosyl thiols are key building blocks for the formation of stable thioglycoside mimetics widespread and biologically relevant α‐ O ‐glycosides, which urges their efficient synthesis. Here, we demonstrate that photoinitiated radical‐mediated addition thioacetic acid to 2‐substituted glycals followed by selective S ‐deacetylation is a generally applicable fully stereoselective method synthesis 1,2‐ cis ‐α‐glycosyl thiols. The low reactivity in radical reaction was overcome carrying out AcOH at −80 °C, frozen state, with UVA irradiation, achieving high yields irrespective sugar configurations. For effective irradiation simultaneous cooling, self‐made spiral vessel reactor used, also enables large‐scale By subjecting ‐α‐1‐thiosugars second thiol‐ene coupling glycals, 34 trehalose‐type symmetrical unsymmetrical α,α’‐thiodi‐ oligosaccharides were obtained full stereoselectivity. Moreover, oxidation α‐1‐thiosugars provided an easy access α,α’‐diglycosyl disulfides.

Язык: Английский

Процитировано

1
Phenylboronic Acid-Modified Polyethyleneimine: A Glycan-Targeting Anti-Biofilm Polymer for Inhibiting Bacterial Adhesion to Mucin and Enhancing Antibiotic Efficacy DOI Creative Commons

Lorcan J. P. Rooney,

Andrew Marshall, Michael M. Tunney

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Bacterial biofilms present significant therapeutic challenges due to their resistance conventional antimicrobial treatment. Mucins typically serve as a protective barrier against pathogens, yet certain bacteria, such Pseudomonas aeruginosa (P. aeruginosa), can exploit these glycoproteins attachment sites for biofilm formation. This study introduces boronic acid-functionalized polyethyleneimine (PEI-BA) promising antibiofilm agent that effectively blocks bacterial adhesion mucin-rich surfaces. Through the multivalent presentation of acid groups, PEI-BA reversibly forms boronate ester bonds with mucin glycans, creating barrier. Our findings show prevents through nonbactericidal mechanism, potentially reducing risk development. Notably, synergizes antibiotic, tobramycin, significantly enhancing inhibition compared either treatment alone. Systematic evaluation formulations identified optimal functionalization levels, balancing glycan-binding capability solubility. From biomaterials design perspective, we demonstrate how rational polymer modification transform potent but cytotoxic (i.e., PEI) into safe and effective material, opening further possibilities managing biofilm-associated infections in clinical settings. work establishes acid-based nanomaterials candidates prevention antibiotic enhancement, particularly conditions like cystic fibrosis, where mucin-bacterial interactions contribute disease progression.

Язык: Английский

Процитировано

1
Fucosyl glycosides for DC-SIGN targeting: Fucosylation strategies, synthesis and binding studies of model compounds DOI

RP Chavan,

Jonathan Lefèbre,

Kateřina Jochová

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118164 - 118164

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion DOI Creative Commons

Leon M. Friedrich,

Thisbe K. Lindhorst

Beilstein Journal of Organic Chemistry, Год журнала: 2025, Номер 21, С. 736 - 748

Опубликована: Апрель 8, 2025

Carbohydrate recognition is fundamental to a plethora of cellular processes and hence the elucidation structural determinants process prerequisite for understanding manipulating carbohydrate-protein interactions, such as in inhibition carbohydrate-specific bacterial adhesion. For receptor binding, glycoligands have be properly oriented three-dimensional space additionally, secondary interactions exerted by multivalent an effect on affinity. A recently introduced orthogonally photoswitchable heterobivalent azobenzene Glc/Man glycocluster was utilized examine these aspects carbohydrate adhesion-inhibition assay. The measured results were systematically contextualized employing new reference compounds respective homobivalent Man/Man glycocluster. An in-depth study comprising analysis photochromic properties potential inhibitors adhesion synthetic glycophotoswitches their different isomeric states led insights into role ligand orientation recognition. experimental underpinned molecular modeling.

Язык: Английский

Процитировано

1
Glycolanguage of the oral microbiota DOI Creative Commons
Fiona F. Hager‐Mair, Susanne Bloch, Christina Schäffer

и другие.

Molecular Oral Microbiology, Год журнала: 2024, Номер 39(5), С. 291 - 320

Опубликована: Март 21, 2024

The oral cavity harbors a diverse and dynamic bacterial biofilm community which is pivotal to health maintenance and, if turning dysbiotic, can contribute various diseases. Glycans as unsurpassed carriers of biological information are participating in underlying processes that shape disease. Bacterial glycoinfrastructure-encompassing compounds glycoproteins, lipopolysaccharides (LPSs), cell wall glycopolymers, exopolysaccharides-is well known influence fitness, with direct effects on physiology, immunogenicity, lifestyle, interaction colonization capabilities. Thus, understanding bacterias' glycoinfrastructure encoded glycolanguage key elucidating their pathogenicity mechanisms developing targeted strategies for therapeutic intervention. Driven by immunological role, most research glycobiology has been directed onto LPSs, whereas, recently, glycoproteins have gaining increased interest. This review draws multifaceted picture the glycolanguage, focus manifested prominent bacteria, such streptococci, Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum. We first define characteristics different glycoconjugate classes then summarize current status knowledge structural diversity glycoconjugates produced describe governing biosynthetic pathways, list roles these energetically costly compounds. Additionally, we highlight emerging unraveling impact dental caries, periodontitis, systemic conditions. By integrating identifying gaps, this underscores importance studying bacteria speak advance our microbiology develop novel antimicrobials.

Язык: Английский

Процитировано

6
Secondary Sites of the C‐type Lectin‐Like Fold DOI Creative Commons
Jonathan Lefèbre, Torben Falk, Yunzhan Ning

и другие.

Chemistry - A European Journal, Год журнала: 2024, Номер 30(30)

Опубликована: Март 25, 2024

C-type lectins are a large superfamily of proteins involved in multitude biological processes. In particular, their involvement immunity and homeostasis has rendered them attractive targets for diverse therapeutic interventions. They share characteristic lectin-like domain whose adaptability enables to bind broad spectrum ligands beyond the originally defined canonical Ca

Язык: Английский

Процитировано

4