Publications by authors named "Ciaran O Reilly"

Carbohydrate-decorated clusters (glycoclusters) centred on a Ru(ii) ion were synthesised and tested for their activity against biofilm formation. These clusters were designed by conjugating a range of carbohydrate motifs (galactose, glucose, mannose and lactose, as well as galactose with a triethylene glycol spacer) to a btp (2,6-bis(1,2,3-triazol-4-yl)pyridine) scaffold. This scaffold, which possesses a symmetry, is an excellent ligand for d-metal ions, and thus the formation of the Ru(ii)-centred glycoclusters 7 and 8Gal was achieved from 5 and 6Gal; each possessing four deprotected carbohydrates.

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Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis. : In this study, aerosolized drug-loaded nanoparticles containing SCD-19, an inhibitor of MIF's tautomerase enzymatic activity, were developed and characterized. The aerosolized nanoparticles had an optimal droplet size distribution for deep lung deposition, with a high degree of biocompatibility and significant cellular uptake.

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Compounds targeting multiple proteins can have synergistic effects and are therefore of interest in medicinal chemistry. At the same time, inhibiting protein-protein interactions (PPI) is increasingly desired in the treatment of disorders or diseases. The development of non-peptidomimetic inhibitors is still a challenge.

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Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator that we have previously shown to be associated with an aggressive clinical phenotype in cystic fibrosis. It possesses unique tautomerase enzymatic activity. However, to date, no human-derived substrate has been identified that has the capacity to interact with this cytokine's unique tautomerase activity.

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Strong evidence has been presented linking chronic inflammation to the onset and pathogenesis of cancer. The multifunctional pro-inflammatory protein macrophage migration inhibitory factor (MIF) occupies a central role in the inflammatory pathway and has been implicated in the tumorigenesis, angiogenesis, and metastasis of many cancer phenotypes. This review highlights the current state of the art, which presents MIF, and the second member of the MIF structural superfamily, D-DT (MIF2), as significant mediators in the inflammatory-cancer axis.

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The cytokine macrophage migration inhibitory factor (MIF) possesses unique tautomerase enzymatic activity, which contributes to the biological functional activity of MIF. In this study, we investigated the effects of blocking the hydrophobic active site of the tautomerase activity of MIF in the pathogenesis of lung cancer. To address this, we initially established a Lewis lung carcinoma (LLC) murine model in Mif-KO and wild-type (WT) mice and compared tumor growth in a knock-in mouse model expressing a mutant MIF lacking enzymatic activity (Mif (P1G)).

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A build-couple-pair strategy, including double-reductive amination macrocyclization, has been used to generate decorated macrocycles (eannaphanes) with an embedded triazole and monosaccharide. Biological screening led to the identification of an inducer of apoptosis in leukemic cells, which acts at least partially as a 5-HT2 antagonist.

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Analogues of glycolipids from Spingomonadacaece with O- and S- and SO2-linkages have been prepared using chelation induced anomerisation promoted by TiCl4. Included are examples of the anomerisation of intermediates with O- and S-glycosidic linkages as well as isomerisation of β-thioglycuronic acids (β-glycosyl thiols). The β-O-glucuronide and β-O-galacturonide precursors were efficiently prepared using benzoylated trichloroacetimidates.

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The synthesis of S-glycosphingolipids based on uronic acids is described. These compounds are analogous to the highly immunostimulatory antigens isolated from the cell walls of bacteria of the Sphingomonas family. Key to the synthetic route is a stereoselective anomerization to give α-glycosyl thiol precursors.

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