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Fluorometric nanoprobes for detection of trehalase activity, based on trehalase-functionalised quantum dots (QDs) are reported.

A radical mediated approach to macrocyclisation of unprotected peptides via Thiol-Ene Click for synthesis of disulfide analogues is reported.

In this review glycosidase activated prodrugs that target cancer cells are discussed. Glycosylated prodrugs undergo enzymatic bioconversion, cleaving the prodrug to release the anticancer drug at the desired site of action, hence minimising the toxic side effects associated with many current anticancer drugs. In addition, the presence of the carbohydrate moiety increases the aqueous solubility of the drugs, allowing for a more effective treatment. In the past decade, significant advancements have been made in this field that have led to the development of many novel carbohydrate-based prodrugs - ranging from simple glycoconjugates to complex self-assemblies and materials, which are discussed in detail herein.

Peer reviewed: True, Funder: Trinity College Dublin; FundRef: http://dx.doi.org/10.13039/501100001637, Macrophages are a highly adaptive population of innate immune cells. Polarization with IFNγ and LPS into the 'classically activated' M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating bacteria such as Mycobacterium tuberculosis. By contrast, 'alternatively activated' M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here, we demonstrate that activation with IL-4 and IL-13 counterintuitively induces protective innate memory against mycobacterial challenge. In human and murine models, prior activation with IL-4/13 enhances pro-inflammatory cytokine secretion in response to a secondary stimulation with mycobacterial ligands. In our murine model, enhanced killing capacity is also demonstrated. Despite this switch in phenotype, IL-4/13 trained murine macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4/13 trained macrophages. Lastly, this work identifies that IL-10 attenuates protective IL-4/13 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection.

Protein aggregation in biotherapeutics has been identified to increase immunogenicity, leading to immune-mediated adverse effects, such as severe allergic responses including anaphylaxis. The induction of anti-drug antibodies (ADAs) moreover enhances drug clearance rates, and can directly block therapeutic function. In this review, identified immune activation mechanisms triggered by protein aggregates are discussed, as well as physicochemical properties of aggregates, such as size and shape, which contribute to immunogenicity. Furthermore, factors which contribute to protein stability and aggregation are considered. Lastly, with these factors in mind, we encourage an innovative and multidisciplinary approach with regard to further research in the field, with the overall aim to avoid immunogenic aggregation in future drug development., Protein aggregation of biotherapeutics increases their immunogenicity, leading to immune-mediated adverse effects. In this review we discuss immune activation pathways, causes of aggregation and mitigation strategies.

Macrophages are key immune cells for combatting Mycobacterium tuberculosis. However, M. tuberculosis possesses means to evade macrophage bactericidal responses by, for instance, secretion of the immunomodulatory para-hydroxybenzoic acid derivatives (pHBADs). While these molecules have been implicated in inhibiting macrophage responses in an acute context, little is known about their ability to reprogram macrophages via induction of long-term innate memory. Since innate memory has been highlighted as a promising strategy to augment bactericidal immune responses against M. tuberculosis, investigating corresponding immune evasion mechanisms is highly relevant. Our results reveal for the first time that pHBAD I and related molecules (unmethylated pHBAD I and the hexose l-rhamnose) reduce macrophage bactericidal mechanisms in both the short- and the long-term. Moreover, we demonstrate how methyl-p-anisate hinders bactericidal responses soon after exposure yet results in enhanced pro-inflammatory responses in the long-term. This work highlights new roles for these compounds in M. tuberculosis pathogenesis.

Real-timetracking of pro drug up take, delivery and activation in vivore presents a major challenge for prodrug development. Here in, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimag-ing, offering unique insight into the prodrug pharmaco kinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.

Carbohydrates are an essential class of biomolecule and carbohydrate active enzymes (CAZys) catalyze their synthesis, refinement, and degradation, hence contributing an overall regulatory capacity to their underpinning physiological roles. Here we survey recent accomplishments for accessing defined carbohydrate structures, suitably equipped with FRET probe capability, followed by their utilization in studying particular classes of CAZy.

Carbohydrates are an essential class of biomolecule and carbohydrate active enzymes (CAZys) catalyze their synthesis, refinement, and degradation, hence contributing an overall regulatory capacity to their underpinning physiological roles. Here we survey recent accomplishments for accessing defined carbohydrate structures, suitably equipped with FRET probe capability, followed by their utilization in studying particular classes of CAZy.

Nature harnesses the unique properties of cysteinyl radical intermediates for a diverse range of essential biological transformations including DNA biosynthesis and repair, metabolism, and biological photochemistry. In parallel, the synthetic accessibility and redox chemistry of cysteinyl radicals renders them versatile reactive intermediates for use in a vast array of synthetic applications such as lipidation, glycosylation and fluorescent labelling of proteins, peptide macrocyclization and stapling, desulfurisation of peptides and proteins, and development of novel therapeutics. This review provides the reader with an overview of the role of cysteinyl radical intermediates in both chemical synthesis and biological systems, with a critical focus on mechanistic details. Direct insights from biological systems, where applied to chemical synthesis, are highlighted and potential avenues from nature which are yet to be explored synthetically are presented.

International audience; Surface modification of electrodes with glycans was investigated as a strategy for modulating the development of electrocatalytic biofilms for microbial fuel cell applications. Covalent attachment of phenyl-mannoside and phenyl-lactoside adlayers on graphite rod electrodes was achieved via electrochemically assisted grafting of aryldiazonium cations from solution. To test the effects of the specific bio-functionalities, modified and unmodified graphite rods were used as anodes in two-chamber microbial fuel cell devices. Devices were set up with wastewater as inoculum and acetate as nutrient and their performance, in terms of output potential (open circuit and 1 kΩ load) and peak power output, was monitored over two months. The presence of glycans was found to lead to significant differences in startup times and peak power outputs. Lactosides were found to inhibit the development of biofilms when compared to bare graphite. Mannosides were found, instead, to promote exoelectrogenic biofilm adhesion and anode colonization, a finding that is supported by quartz crystal microbalance experiments in inoculum media. These differences were observed despite both adlayers possessing thickness in the nm range and similar hydrophilic character. This suggests that specific glycan-mediated bioaffinity interactions can be leveraged to direct the development of biotic electrocatalysts in bioelectrochemical systems and microbial fuel cell devices.

Carbohydrates are an essential class of biomolecule and carbohydrate active enzymes (CAZys) catalyse their synthesis, refinement, and degradation, hence contributing an overall regulatory capacity to their underpinning physiological roles. As such, there is a considerable current requirement to be able to monitor, quantify and inhibit CAZy activity. It is here that Forster resonance energy transfer (FRET) is emerging as a powerful tool in enabling this, through synthetic conjugation of appropriate fluorogenic partners into a particular CAZy substrate. In this review we survey recent accomplishments in synthetic methodology for accessing defined carbohydrate structures, suitably equipped with FRET probe capability, followed by their utilisation in studying particular classes of CAZy. The majority of examples concern endo-acting glycosidases, but emergent probes for exo-glycosidases, glycosyl transferases and catalytic antibodies are also examined.

A novel strategy for the synthesis of δ-thiolactones from inexpensive and readily available γ-unsaturated esters has been developed. This strategy incorporates a radical acyl thiol-ene reaction as the key C-S bond forming step. Cyclization is achieved via a Steglich-type thiolactonization of 5-mercaptopentanoic acids. We report the facile and scalable synthesis of δ-thiolactones in moderate to good yield under mild reaction conditions with tolerance for a range of functional groups.

International audience; Grafting of aryldiazonium cations bearing a p-mannoside functionality over microbial fuel cell (MFC) anode materials was performed to investigate the ability of aryl-glycoside layers to regulate colonisation by biocatalytic biofilms. Covalent attachment was achieved via spontaneous reactions and via electrochemically-assisted grafting using potential step experiments. The effect of different functionalisation protocols on MFC performance is discussed in terms of changes in wettability, roughness and electrochemical response of modified electrodes. Water contact angle measurements (WCA) show that aryl-mannoside grafting yields a significant increase in hydrophilic character. Surface roughness determinations via atomic force microscopy (AFM) suggest a more disordered glycan adlayer when electrografting is used to facilitate chemisorption. MFCs were used as living sensors to successfully test the coated electrodes the response of the MFCs in terms of start-up time was accelerated when compared to that of MFC equipped with non-modified electrodes, this suggests a faster development of a mature biofilm community resulting from aryldiazonium modifications, as confirmed by cyclic voltammetry of MFC anodes. These results therefore indicate that modification with glycans offers a bioinspired route to accelerating biofilm colonisation without any adverse effects on final MFC outputs.

Radical thiol-ene chemistry has been demonstrated for a range of applications in peptide science, including macrocyclisation, glycosylation and lipidation amongst a myriad of others. The thiol-ene reaction offers a number of advantages in this area, primarily those characteristic of “click” reactions. This provides a chemical approach to peptide modification that is compatible with aqueous conditions with high orthogonality and functional group tolerance. Additionally, the use of a chemical approach for peptide modification affords homogeneous peptides, compared to heterogeneous mixtures often obtained through biological methods. In addition to peptide modification, thiol-ene chemistry has been applied in novel approaches to biological studies through synthesis of mimetics and use in development of probes. This review will cover the range of applications of the radical-mediated thiol-ene reaction in peptide and protein science.

Macrophages are key immune cells for combatting

A mild, metal-free, atmospheric oxygen-mediated radical hydrothiolation of alkenes (and alkyne) is reported. A variety of sulfur containing motifs including alkanethiols, thiophenols and thioacids undergo an atmospheric oxygen-mediated radical hydrothiolation reaction with a plethora of alkenes in good yield with excellent functional group compatibility, typically with short reaction times to furnish a range of functionalised products. Biomolecules proved tolerant to the conditions and the procedure is robust and easily executable requiring no specialised equipment. Concise mechanistic studies confirm the process proceeds through radical intermediates in a thiol-ene reaction manifold. The methodology offers an efficient 'green' approach for thiol-ene mediated 'click' ligation and a milder alternative to thermally initiated hydrothiolation processes.

An investigation into the self-assembly of two 4-amino- and a 4-bromo-1,8-naphthalimide (Nap) based structures (1-3) possessing an appended glycan unit, from protic polar media, is presented. The results demonstrate the formation of complex hierarchical luminescent aggregates, wherein the morphologies, sizes and spherical structures were highly dependent on both the media and the Nap structure. Upon cleaving the native glycosidic bond, using an enzyme, the structure/morphology of the self-assembly of 3 in buffered solution was significantly transformed.

A mild and efficient surface modification protocol for the preparation of β-cyclodextrin (βCD) modified surfaces through aryldiazonium-mediated grafting is reported. Monosubstituted 6-O-aminophenol-β-cyclodextrin (amβCD) was synthesized through a three-step protocol. This compound was found to form supramolecular aggregates in aqueous solutions at relatively low concentrations via cavity-directed self-assembly. Disruption of these supramolecular structures through judicious choice of solvent was found to be essential for the formation of the reactive aryldiazonium species from the amino-phenolic precursor and for spontaneous surface grafting from aqueous solutions. Cyclodextrin thin films were prepared on carbon macroscopic substrates and electrodes and were characterized via infrared reflectance absorption spectroscopy (IRRAS), cyclic voltammetry, and water contact angle measurements. Protein adsorption studies demonstrated that βCD adlayers reduced nonspecific protein adsorption. βCD moieties in adlayer...

Surface treatments that minimize biofouling in marine environments are of interest for a variety of applications such as environmental monitoring and aquaculture. We report on the effect of saccharide coatings on biomass accumulation at the surface of three materials that find applications in marine settings: stainless steel 316 (SS316), Nylon-6 (N-6), and poly(ether sulfone) (PES). Saccharides were immobilized via aryldiazonium chemistry; SS316 and N-6 samples were subjected to oxidative surface pretreatments prior to saccharide immobilization, whereas PES was modified via direct reaction of pristine surfaces with the aryldiazonium cations. Functionalization was confirmed by a combination of X-ray photoelectron spectroscopy, contact angle experiments, and fluorescence imaging of lectin–saccharide binding. Saccharide immobilization was found to increase surface hydrophilicity of all materials tested, while laboratory tests demonstrate that the saccharide coating results in reduced protein adsorption in the absence of specific protein–saccharide interactions. The performance of all three materials after modification with aryldiazonium saccharide films was tested in the field via immersion of modified coupons in coastal waters over a 20 day time period. Results from combined infrared spectroscopy, light microscopy, scanning electron and He-ion microscopy, and adenosine-triphosphate content assays show that the density of retained biomass at surfaces is significantly lower on carbohydrate modified samples with respect to unmodified controls. Therefore, functionalization and field test results suggest that carbohydrate aryldiazonium layers could find applications as fouling resistant coatings in marine environments.

It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal “classically activated” M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial – for example the successful introduction of biomedical implants. Although there are numerous endogenous and exogenous factors that have an impact on the macrophage polarisation spectrum, this review will focus specifically on prominent macrophage-modulating carbohydrate motifs with a view towards highlighting structure–function relationships and therapeutic potential.

S-to-N acyl transfer is a high-yielding chemoselective process for amide bond formation. It is widely utilized by chemists for synthetic applications, including peptide and protein synthesis, chemical modification of proteins, protein-protein ligation and the development of probes and molecular machines. Recent advances in our understanding of S-to-N acyl transfer processes in biology and innovations in methodology for thioester formation and desulfurization, together with an extension of the size of cyclic transition states, have expanded the boundaries of this process well beyond peptide ligation. As the field develops, this chemistry will play a central role in our molecular understanding of Biology., The conversion of thioesters to amides via acyl transfer has become one of the most important synthetic techniques for the chemical synthesis and modification of proteins. This review discusses this S-to-N acyl transfer process, and highlights some of the key applications across chemistry and biology.

Carbon nano-onions (CNOs) possess favorable properties that make them suitable for biomedical applications, including their small size, ready surface modification, and good biocompatibility. Here, we report the covalent immobilization of a synthetic glycopeptide and the protein bovine serum albumin (BSA) onto the surface of carbon nano-onions using the maleimide&ndash, thiol &ldquo, addition reaction&rdquo, The glycopeptide and BSA are readily transported inside different cell lines, together with carbon nano-onions, through the endocytosis pathway. Our results show that carbon nano-onions are excellent scaffolds for glycopeptides and proteins immobilization and act as intracellular carriers for these biomolecules. These findings open new perspectives in the application of carbon nano-onions as intracellular transporters in diverse biomedical applications.

Dehydroalanine (ΔAla) is a highly electrophilic residue that can react efficiently with sulfur nucleophiles to furnish cysteinyl analogues. Herein, we report an efficient synthesis of N-terminal cysteinyl thioesters, suitable for S, N-acyl transfer, based on β,γ-C,S thiol-Michael addition. Both ionic and radical-based methodologies were found to be efficient for this process.

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.

Correction for ‘Glycosylated naphthalimides and naphthalimide Tröger's bases as fluorescent aggregation probes for Con A’ by Elena Calatrava-Pérez et al., Org. Biomol. Chem., 2019, DOI: 10.1039/c8ob02980f.

Herein we report the synthesis of fluorescent, glycosylated 4-amino-1,8-naphthalimide (Nap) 1, and the related 1,8-naphthalimides Troger's bases (TBNap) 2 and 3, from 1,8-naphthalic anhydride precursors, the α-mannosides being introduced through the use of CuAAC mediated 'click' chemistry. We investigate the photophysical properties of these probes in buffered solution and demonstrate their ability to function as fluorescent probes for Concanavalin A (Con A) lectin. We show that both the Nap and TBNap structures self-assemble in solution. The formation of the resulting supramolecular structures is driven by head-to-tail π-π stacking and extended hydrogen bonding interactions of the Nap and the triazole moieties. These interactions give rise to spherical nano-structures (ca. 260 nm and 100 nm, for 1 and 3, respectively), which interact with the Con-A protein, the interaction being probed by using both luminescent and Scanning Electron Microscopy imaging as well as dynamic light scattering measurements. Finally, we show that these supramolecular assembles can be used as luminescent imaging agents, through confocal fluorescence imaging of HeLa cells of the per-acetylated version 2.

Glycosylated 4-amino-1,8-naphthalimide derivatives possess a native glycosidic linkage that can be selectively hydrolysed in situ by glycosidase enzymes to release the naphthalimide as a fluorescent imaging or therapeutic agent. In vitro studies using a variety of cancer cell lines demonstrated that the naphthalimides only get taken up into cells upon enzymatic cleavage from the glycan unit; a mechanism that offers a novel approach for the targeted delivery of probes/drugs.

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.

This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.

Herein, we report synthetic strategies towards a library of amphiphilic tetraphenyl porphyrins anchored to synthetic saccharides and lipid modalities. The carbohydrates and lipid functionalities are covalently linked to the model photosensitizer via a copper (I) catalyzed alkyne azide cycloaddition reaction or an oxypropyl linkage achieved by nucleophilic substitution chemistry. Varying substitutions of carbohydrates and lipids allows for potential fine tuning of solubility and photophysical characteristics important for imaging and treatment applications in photomedicine, specifically in photodynamic therapy.

A mild, inexpensive, and general photocatalytic initiation protocol for anti-Markovnikov hydrothiolation of olefins using carbon nanomaterial/metal oxide (carbon NM-MO) composites is reported. Graphene oxide (GO), nanodiamonds (ND), and carbon nano-onions (CNO) displaying bismuth or tungsten oxide nanoparticles adhered to the surface and function as highly efficient photocatalysts for thiol–ene ligation under both UV and visible-light-mediated conditions. The straightforward catalyst preparation, excellent overall yields, ease of purification, and broad substrate scope render this a highly versatile method for bioconjugation.

A new synthetic approach to thiolactones that employs an efficient acyl thiol–ene (ATE) or acyl thiol–yne (ATY) cyclization to convert unsaturated thiocarboxylic acid derivatives into thiolactones under very mild conditions is described. The high overall yields, fast kinetics, high diastereoselectivity, excellent regiocontrol, and broad substrate scope of these reaction processes render this a very useful approach for diversity-oriented synthesis and drug discovery efforts. A detailed computational rationale is provided for the observed regiocontrol.

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.

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.

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.

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 immobi...