Bi- and trivalent glycopeptide mannopyranosides as inhibitors of type 1 fimbriae-mediated bacterial adhesion: variation of valency, aglycon and scaffolding

Schierholt, Alexander; Hartmann, Mirja

doi:10.1016/j.carres.2011.04.023

Cited by 22 publications

(18 citation statements)

References 34 publications

(41 reference statements)

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“…While this focus has largely been replaced by the rational design of orally bioavailable lower molecular monomeric mannosides, several multivalent mannoside inhibitors have been reported, including glycodendrimers and neoglycoproteins [107-108], CD-based HMs [69, 109-114], glycoclusters [115-116], and others [117-120]. While these have been extensively reviewed previously [121-122], we present select examples of smaller, di-and tri-valent mannosides in the following discussion.…”

Section: Multivalent Mannosides: the Promise Of Avidity From Multimentioning

confidence: 99%

Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease

Mydock-McGrane

Hannan

Janetka

2017

Expert Opinion on Drug Discovery

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Introduction The bacterial adhesin FimH is a virulence factor and an attractive therapeutic target for urinary tract infection (UTI) and Crohn's Disease (CD). Located on type 1 pili of uropathogenic E. coli (UPEC), the FimH adhesin plays an integral role in the pathogenesis of UPEC. Recent efforts have culminated in the development of small-molecule mannoside FimH antagonists that target the mannose-binding lectin domain of FimH, inhibiting its function and preventing UPEC from binding mannosylated host cells in the bladder, thereby circumventing infection. Areas covered The authors describe the structure-guided design of mannoside ligands, and review the structural biology of the FimH lectin domain. Additionally, they discuss the lead optimization of mannosides for therapeutic application in UTI and CD, and describe various assays used to measure mannoside potency in vitro and mouse models used to determine efficacy in vivo. Expert opinion To date, mannoside optimization has led to a diverse set of small-molecule FimH antagonists with oral bioavailability. With clinical trials already initiated in CD and on the horizon for UTI, it is the authors opinion that mannosides will be a ‘first-in-class’ treatment strategy for UTI and CD, and will pave the way for treatment of other Gram-negative bacterial infections.

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Section: Multivalent Mannosides: the Promise Of Avidity From Multimentioning

confidence: 99%

Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease

Mydock-McGrane

Hannan

Janetka

2017

Expert Opinion on Drug Discovery

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“…The observed multivalency effects are not fully understood. In a recent study, mannose di- and trivalent glycopeptides were evaluated for their inhibition of FimH binding [107]. The valency, conformational properties, and spatial arrangement of the attached mannose residues were evaluated.…”

Section: Reviewmentioning

confidence: 99%

Synthetic glycopeptides and glycoproteins with applications in biological research

Westerlind¹

2012

Beilstein J. Org. Chem.

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SummaryOver the past few years, synthetic methods for the preparation of complex glycopeptides have been drastically improved. The need for homogenous glycopeptides and glycoproteins with defined chemical structures to study diverse biological phenomena further enhances the development of methodologies. Selected recent advances in synthesis and applications, in which glycopeptides or glycoproteins serve as tools for biological studies, are reviewed. The importance of specific antibodies directed to the glycan part, as well as the peptide backbone has been realized during the development of synthetic glycopeptide-based anti-tumor vaccines. The fine-tuning of native chemical ligation (NCL), expressed protein ligation (EPL), and chemoenzymatic glycosylation techniques have all together enabled the synthesis of functional glycoproteins. The synthesis of structurally defined, complex glycopeptides or glyco-clusters presented on natural peptide backbones, or mimics thereof, offer further possibilities to study protein-binding events.

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“…Due to the complexity of residue notation this structural diversity is a challenge for glycoinformatics, but it also offers many possibilities to synthesize carbohydrates or glycomimetics that target specific pathogen proteins. For example, oligosaccharide motifs that are found in surface carbohydrates of pathogens, but not in host organisms or in symbiotes, can serve as templates in vaccine development [67–70], and glycomimetics that block specific enzymes or lectins can be used for therapeutic purposes [71–77]. …”

Section: Reviewmentioning

confidence: 99%

The use of glycoinformatics in glycochemistry

Lütteke

2012

Beilstein J. Org. Chem.

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Glycoinformatics is a small but growing branch of bioinformatics and chemoinformatics. Various resources are now available that can be of use to glycobiologists, but also to chemists who work on the synthesis or analysis of carbohydrates. This article gives an overview of existing glyco-specific databases and tools, with a focus on their application to glycochemistry: Databases can provide information on candidate glycan structures for synthesis, or on glyco-enzymes that can be used to synthesize carbohydrates. Statistical analyses of glycan databases help to plan glycan synthesis experiments. 3D-Structural data of protein–carbohydrate complexes are used in targeted drug design, and tools to support glycan structure analysis aid with quality control. Specific problems of glycoinformatics compared to bioinformatics for genomics or proteomics, especially concerning integration and long-term maintenance of the existing glycan databases, are also discussed.

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Bi- and trivalent glycopeptide mannopyranosides as inhibitors of type 1 fimbriae-mediated bacterial adhesion: variation of valency, aglycon and scaffolding

Cited by 22 publications

References 34 publications

Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease

Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease

Synthetic glycopeptides and glycoproteins with applications in biological research

The use of glycoinformatics in glycochemistry

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