Eoin M. Scanlan

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Organization: Trinity Biomedical Sciences Institute , Ireland

Department: Trinity College

Title: Assistant Professor(PhD)

TOPICS

Organic Chemistry

Oligosaccharide Synthesis

Polymer

Polysulfone

Chemicals
References

The Emergence of Phenolic Glycans as Virulence Factors in Mycobacterium tuberculosis

Co-reporter:Danielle D. Barnes, Mimmi L. E. Lundahl, Ed C. Lavelle, and Eoin M. Scanlan

ACS Chemical Biology August 18, 2017 Volume 12(Issue 8) pp:1969-1969

Publication Date(Web):July 10, 2017

DOI:10.1021/acschembio.7b00394

Tuberculosis is the leading infectious cause of mortality worldwide. The global epidemic, caused by Mycobacterium tuberculosis, has prompted renewed interest in the development of novel vaccines for disease prevention and control. The cell envelope of M. tuberculosis is decorated with an assortment of glycan structures, including glycolipids, that are involved in disease pathogenesis. Phenolic glycolipids and the structurally related para-hydroxybenzoic acid derivatives display potent immunomodulatory activities and have particular relevance for both understanding the interaction of the bacterium with the host immune system and also in the design of new vaccine and therapeutic candidates. Interest in glycobiology has grown exponentially over the past decade, with advancements paving the way for effective carbohydrate based vaccines. This review highlights recent advances in our understanding of phenolic glycans, including their biosynthesis and role as virulence factors in M. tuberculosis. Recent chemical synthesis approaches and biochemical analysis of synthetic glycans and their conjugates have led to fundamental insights into their roles in host–pathogen interactions. The applications of these synthetic glycans as potential vaccine candidates are discussed.

Supramolecular Anion Recognition Mediates One-Pot Synthesis of 3-Amino-[1,2,4]-triazolo Pyridines from Thiosemicarbazides

Co-reporter:Komala Pandurangan, Anna B. Aletti, Devis Montroni, Jonathan. A. Kitchen, Miguel Martínez-Calvo, Salvador Blasco, Thorfinnur GunnlaugssonEoin M. Scanlan

Organic Letters 2017 Volume 19(Issue 5) pp:

Publication Date(Web):February 21, 2017

DOI:10.1021/acs.orglett.6b03645

A facile one-pot synthesis of 3-amino-[1,2,4]-triazolo[4,3-a]pyridines from thiosemicarbazides through anion mediated synthesis is reported. Thiosemicarbazides derived from 2-hydrazino pyridine, 5-chloro 2-hydrazino pyridine, and 2-hydrazine quinoline were formed in situ as anion receptors in the presence of TBAF. Under microwave heating, thiosemicarbazides furnished the triazolo pyridines in good to moderate yields. The formation of the thiosemicarbazides hydrogen bonding anion receptors was critical in cascading the reaction toward the formation of the triazolo pyridines.

Thiyl-Radical Reactions in Carbohydrate Chemistry: From Thiosugars to Glycoconjugate Synthesis

Co-reporter:Lauren McSweeney;Fabrice Dénès

European Journal of Organic Chemistry 2016 Volume 2016( Issue 12) pp:2080-2095

Publication Date(Web):

DOI:10.1002/ejoc.201501543

Abstract

Thiyl-radical mediated reactions have been extensively investigated for the preparation of carbohydrate derivatives. Due to the mild reaction conditions, high yields and tolerance to a wide range of functional groups, these reactions are ideally suited to the preparation of bioconjugates including glycopeptides and glycoproteins. This microreview covers the various synthetic strategies that have been employed for the preparation of thiosugars, glycoconjugates and glycodendrimers, employing the carbohydrate unit as both the carrier of the thiyl radical and also as the acceptor. Both the inter- and intramolecular thiol-ene and -yne processes are presented and discussed. Future perspective and directions for this methodology in glycoscience are also examined.

Stable hydrophilic poly(dimethylsiloxane) via glycan surface functionalization

Co-reporter:Leticia Esteban-Tejeda, Thomas Duff, Guido Ciapetti, M. Daniela Angione, Adam Myles, Joana M. Vasconcelos, Eoin M. Scanlan, Paula E. Colavita

Polymer 2016 Volume 106() pp:1-7

Publication Date(Web):5 December 2016

DOI:10.1016/j.polymer.2016.10.044

•Functionalization of PDMS was successfully achieved using a solution based method.•Long term wettability was achieved via grafting of aryldiazonium glycosides.•Surface bound glycans are recognized at PDMS surfaces by lectins.Polydimethylsiloxane (PDMS) is an extremely important and versatile polymeric material for biomedical and microfluidic devices due to a range of desirable properties. Control of the hydrophilicity of PDMS surfaces is of significant interest due to the potential for developing surfaces with tunable protein adsorption or cell adhesion properties. We report the formation of stable hydrophilic PDMS surfaces by covalent modification with glycans via aryldiazonium chemistry. The PDMS surface was modified by a two step-process including an activation of the PDMS surface, followed by reaction with aryldiazonium glycosides in aqueous solution. The functionalized PDMS was characterized by atomic force microscopy, infrared and X-ray photoelectron spectroscopy, water contact angle measurements and fluorescence microscopy. Our results demonstrate that glycans immobilized via this methodology have the dual function of imparting hydrophilicity and stabilizing the modified surface against hydrophobic recovery. Importantly, the presentation of thus immobilized glycosides makes them available to specific lectin-glycan binding interactions at the polymer-solution interface while, in the absence of specific binding interactions, leads to a reduction in albumin adsorption. This approach provides a novel and efficient route to stable hydrophilic PDMS surfaces with a broad range of applications.

Intramolecular thiol–yne cyclisation as a novel strategy for thioglycal synthesis

Co-reporter:Vincent Corcé, Lauren McSweeney, Aoife Malone and Eoin M. Scanlan

Chemical Communications 2015 vol. 51(Issue 41) pp:8672-8674

Publication Date(Web):20 Apr 2015

DOI:10.1039/C5CC02162F

A novel intramolecular thiol–yne cyclisation strategy has been developed for the synthesis of thioglycals. Both ionic and radical mediated cyclisation pathways have been investigated for D- and L-sugars. The ionic cyclisation provides exclusive access to 5-exo products directly from the thioesters whereas the radical cyclisation provides access to both 5-exo and 6-endo products upon photochemical irradiation of the free thiols. These are the first examples of intramolecular thiol–yne cyclisation reactions applied to thiosugar synthesis.

Recent advances in the development of synthetic chemical probes for glycosidase enzymes

Co-reporter:Helen M. Burke, Thorfinnur Gunnlaugsson and Eoin M. Scanlan

Chemical Communications 2015 vol. 51(Issue 53) pp:10576-10588

Publication Date(Web):02 Jun 2015

DOI:10.1039/C5CC02793D

The emergence of synthetic glycoconjugates as chemical probes for the detection of glycosidase enzymes has resulted in the development of a range of useful chemical tools with applications in glycobiology, biotechnology, medical and industrial research. Critical to the function of these probes is the preparation of substrates containing a glycosidic linkage that when activated by a specific enzyme or group of enzymes, irreversibly releases a reporter molecule that can be detected. Starting from the earliest examples of colourimetric probes, increasingly sensitive and sophisticated substrates have been reported. In this review we present an overview of the recent advances in this field, covering an array of strategies including chromogenic and fluorogenic substrates, lanthanide complexes, gels and nanoparticles. The applications of these substrates for the detection of various glycosidases and the scope and limitations for each approach are discussed.

Enhanced Antifouling Properties of Carbohydrate Coated Poly(ether sulfone) Membranes

Co-reporter:M. Daniela Angione, Thomas Duff, Alan P. Bell, Serban N. Stamatin, Cormac Fay, Dermot Diamond, Eoin M. Scanlan, and Paula E. Colavita

ACS Applied Materials & Interfaces 2015 Volume 7(Issue 31) pp:17238

Publication Date(Web):July 20, 2015

DOI:10.1021/acsami.5b04201

Poly(ether sulfone) membranes (PES) were modified with biologically active monosaccharides and disaccharides using aryldiazonium chemistry as a mild, one-step, surface-modification strategy. We previously proposed the modification of carbon, metals, and alloys with monosaccharides using the same method; herein, we demonstrate modification of PES membranes and the effect of chemisorbed carbohydrate layers on their resistance to biofouling. Glycosylated PES surfaces were characterized using spectroscopic methods and tested against their ability to interact with specific carbohydrate-binding proteins. Galactose-, mannose-, and lactose-modified PES surfaces were exposed to Bovine Serum Albumin (BSA) solutions to assess unspecific protein adsorption in the laboratory and were found to adsorb significantly lower amounts of BSA compared to bare membranes. The ability of molecular carbohydrate layers to impart antifouling properties was further tested in the field via long-term immersive tests at a wastewater treatment plant. A combination of ATP content assays, infrared spectroscopic characterization and He-ion microscopy (HIM) imaging were used to investigate biomass accumulation at membranes. We show that, beyond laboratory applications and in the case of complex aqueous environments that are rich in biomass such as wastewater effluent, we observe significantly lower biofouling at carbohydrate-modified PES than at bare PES membrane surfaces.Keywords: antifouling; biomimetic; carbohydrates; coatings; membranes; poly(ether sulfone)

The synthesis and biological evaluation of mycobacterial p-hydroxybenzoic acid derivatives (p-HBADs)

Co-reporter:Jean Bourke, Corinna F. Brereton, Stephen V. Gordon, Ed C. Lavelle and Eoin M. Scanlan

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 7) pp:1114-1123

Publication Date(Web):23 Dec 2013

DOI:10.1039/C3OB42277A

Mycobacterium tuberculosis establishes chronic infection and causes disease through manipulation of the host's innate and adaptive immune response. The bacterial cell wall is highly complex and contains a rich variety of glycosylated compounds that are secreted during infection and have been proposed as immunomodulatory molecules. Amongst the most important of these are the p-hydroxybenzoic acid derivatives (p-HBADs). Here we report the synthesis of this important class of biomolecules and the first in vitro study of the immunomodulatory effects of these compounds in isolation from the host bacterium. The compounds do not have stimulatory properties but, in contrast, can inhibit the production of inflammatory cytokines, particularly interferon-γ (IFN-γ), by T-cells. This study offers a fundamental insight into the effect of these glycans on the immune response.

Carbohydrate Coatings via Aryldiazonium Chemistry for Surface Biomimicry

Co-reporter:Dilushan R. Jayasundara, Thomas Duff, M. Daniela Angione, Jean Bourke, Deirdre M. Murphy, Eoin M. Scanlan, and Paula E. Colavita

Chemistry of Materials 2013 Volume 25(Issue 20) pp:4122

Publication Date(Web):September 24, 2013

DOI:10.1021/cm4027896

Carbohydrates are extremely important biomolecules and their immobilization onto solid surfaces is of interest for the development of new biomimetic materials and of new methods for understanding processes in glycobiology. We have developed an efficient surface modification methodology for the functionalization of a range of materials with biologically active carbohydrates based on aryldiazonium chemistry. We describe the synthesis and characterization of carbohydrate reagents, which were subsequently employed for the one-step, solution-based modification of carbon, metals, and alloys with monosaccharides. We used a combination of spectroscopic and nanogravimetric methods to characterize the structure of the carbohydrate layers; we report an average surface coverage of 7.8 × 10–10 mol cm–2 under our experimental conditions. Concanavalin A, a mannose-binding lectin, and Peanut Agglutinin, a galactose-binding lectin, were found to bind from solution to their respective monosaccharide binding partners immobilized at the surface. This result suggests that the spontaneous chemisorption of aryldiazonium monosaccharide precursors leads to the formation of monosaccharide layers that retain the biological recognition specificity of the parent carbohydrate molecule. Finally, we carried out measurements using fluorescently labeled Bovine Serum Albumin (BSA) and found that these carbohydrate coatings reduce unspecific adsorption of this protein at carbon surfaces. These results suggest that aryldiazonium-derived carbohydrate coatings may offer a promising strategy for preventing undesirable protein accumulation onto surfaces.Keywords: carbohydrate; carbon; coatings; diazonium; saccharide;

Applications of Thiyl Radical Cyclizations for the Synthesis of Thiosugars

Co-reporter:Aoife Malone and Eoin M. Scanlan

Organic Letters 2013 Volume 15(Issue 3) pp:504-507

Publication Date(Web):January 18, 2013

DOI:10.1021/ol303310u

The use of intramolecular thiyl radical cyclizations for the synthesis of thiosugars has been investigated, and a new free-radical-based methodology for the synthesis of biologically important thiosugars has been developed. The methodology is mild and proceeds via either 6-endo or 5-exo cyclization to furnish the thiosugar ring. This represents the first examples of thiyl radical cyclization being applied to the synthesis of thiosugars.

An unusual glycosylation product from a partially protected fucosyl donor under silver triflate activation conditions

Co-reporter:Robin Daly and Eoin M. Scanlan

Organic & Biomolecular Chemistry 2013 vol. 11(Issue 48) pp:8452-8457

Publication Date(Web):31 Oct 2013

DOI:10.1039/C3OB42073F

Partially protected glycosyl donors are extremely useful reagents for oligosaccharide synthesis allowing more facile deprotection and enhanced activity due to lower steric restraints. A partially protected fucosyl donor containing tert-butyldimethylsilyl (TBDMS) protecting groups was activated under bromine–silver triflate conditions in the presence of primary alcohols and found to give difucoside products exclusively, in good yield with excellent diastereoselectivity. The dimerisation reaction appears to require a conformational relaxation of steric crowding, induced upon activation of the glycosyl donor. The scope and limitations of this unusual glycosylation methodology are reported.

Applications of 5-exo-trig Thiyl Radical Cyclizations for the Synthesis of Thiosugars

Co-reporter:Aoife Malone and Eoin M. Scanlan

The Journal of Organic Chemistry 2013 Volume 78(Issue 21) pp:10917-10930

Publication Date(Web):September 30, 2013

DOI:10.1021/jo401900e

The application of thiyl-radical-mediated 5-exo-trig cyclization reactions for the preparation of a series of C-linked 4-thiofuranoside sugars has been investigated. The cyclization reactions were found to proceed in high yield with complete regioselectivity and moderate to excellent diastereoselectivity for a number of benzyl-protected precursors. The diastereoselectivity of the radical cyclization was determined by a number of factors, primarily the stereochemistry at the C-2 position and the nature of the substituents attached to the olefin. The cyclization reactions proceed via transition-state intermediates that favor formation of the 1,2-trans products. For d-sugars, a chairlike transition state is proposed. For l-sugars, both chair- and boatlike transition states could be considered. Inversion of the stereochemistry at C-4 also induced a significant effect on the diastereoselectivity of the radical process. The synthetic route is general for both d- and l-sugars and offers a highly novel and efficient strategy for accessing C-linked 4-thiofuranosides. A fluorescently labeled thiosugar was prepared as a putative glycosidase inhibitor.

Native Chemical Ligation,Thiol–Ene Click: A Methodology for the Synthesis of Functionalized Peptides

Co-reporter:Lyn Markey, Silvia Giordani, and Eoin M. Scanlan

The Journal of Organic Chemistry 2013 Volume 78(Issue 9) pp:4270-4277

Publication Date(Web):April 8, 2013

DOI:10.1021/jo4001542

The sequential combination of native chemical ligation and thiol–ene radical chemistry (NCL-TEC) on the resulting cysteine thiol has been investigated as a methodology for rapidly accessing functionalized peptides. Three sequential cycles of native chemical ligation and subsequent thiyl radical reactions (including a free-radical-mediated desulfurization reaction) were carried out on a peptide backbone demonstrating the iterative nature of this process. The versatility of the thiyl radical reaction at cysteine was demonstrated through the introduction of a number of different side chains including an amino acid derivative, a carbohydrate group, and an alkyl azide. Conditions were developed that allowed the sequential NCL-TEC process to proceed in high yield.

Development of Fully and Partially Protected Fucosyl Donors for Oligosaccharide Synthesis

Co-reporter:Robin Daly, Thomas McCabe, and Eoin M. Scanlan

The Journal of Organic Chemistry 2013 Volume 78(Issue 3) pp:1080-1090

Publication Date(Web):December 26, 2012

DOI:10.1021/jo302487c

The use of fully and partially tert-butyldimethylsilyl (TBDMS) protected fucose thioglycosides as glycosyl donors for oligosaccharide synthesis is described. Both the trisilyl- and disilyl-protected thioglycoside donors were prepared, and their reactivity under a range of activation conditions was investigated. Both silyl-protected donors were found to give good yields of the desired α products and the silyl protecting groups could be removed in the presence of unsaturated bonds. The disilyl-protected donor was found to behave as an efficient, partially protected glycosyl donor. The synthetic scope and limitations of these new donors is presented. Both donors were applied to the synthesis of a Lewis X trisaccharide displaying a propargyl group at the anomeric position. It was determined that the additional steric bulk of the TBDMS group inferred unusual reactivity on these fucosyl donors.

Synthesis and Biological Evaluation of a Library of Glycoporphyrin Compounds

Co-reporter:Robin Daly;Gisela Vaz;Dr. Anthony M. Davies;Dr. Mathias O. Senge;Dr. Eoin M. Scanlan

Chemistry - A European Journal 2012 Volume 18( Issue 46) pp:14671-14679

Publication Date(Web):

DOI:10.1002/chem.201202064

Abstract

A library of glycosylated porphyrins (glycoporphyrins) was prepared and the compounds were evaluated for their photodynamic therapy (PDT) activity against the oesophageal squamous-cell carcinoma cell line OE21 in vitro. A synthetic methodology was developed to allow incorporation of biologically active carbohydrates, including the histo-blood-group antigen trisaccharide Lewis^X, onto the porphyrin backbone. The effect of the carbohydrate group and substitution pattern on the PDT activity, cell uptake and subcellular localisation of the glycoporphyrin compounds is reported.

Efficient Synthesis of Glycoporphyrins by Microwave-Mediated Click Reactions

Co-reporter:Oliver B. Locos;Claudia C. Heindl;Ariadna Corral;Mathias O. Senge

European Journal of Organic Chemistry 2010 Volume 2010( Issue 6) pp:1026-1028

Publication Date(Web):

DOI:10.1002/ejoc.200901292

Abstract

The Cu^I-catalysed Huisgen cycloaddition “click” reaction has been applied to the synthesis of a range of triazole-linked glycoporphyrins. The “click” reaction under microwave-heating conditions has been shown to provide a general and robust methodology for the synthesis of mono-, di-, tri- and tetra-modified glycoporphyrins. A sequential “double-click” process was employed to access a new class of bis-modified 5,10-diglycoporphyrins displaying heterogeneous carbohydrates.

Intramolecular thiol–yne cyclisation as a novel strategy for thioglycal synthesis

Co-reporter:Vincent Corcé, Lauren McSweeney, Aoife Malone and Eoin M. Scanlan

Chemical Communications 2015 - vol. 51(Issue 41) pp:NaN8674-8674

Publication Date(Web):2015/04/20

DOI:10.1039/C5CC02162F

Recent advances in the development of synthetic chemical probes for glycosidase enzymes

Co-reporter:Helen M. Burke, Thorfinnur Gunnlaugsson and Eoin M. Scanlan

Chemical Communications 2015 - vol. 51(Issue 53) pp:NaN10588-10588

Publication Date(Web):2015/06/02

DOI:10.1039/C5CC02793D

The synthesis and biological evaluation of mycobacterial p-hydroxybenzoic acid derivatives (p-HBADs)

Co-reporter:Jean Bourke, Corinna F. Brereton, Stephen V. Gordon, Ed C. Lavelle and Eoin M. Scanlan