Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• . [12] in the context of photoswitchable ligands to the lectin LecA. Staying in the theme of lectin characterization, Lundstrøm et al. study the glycan binding profile of CMA1 originating from melon [13]. A time that sees great opportunities in computational biology also breeds innovative applications

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• , (iv) model quality evaluation. Each of the above processes may be repeated interactively until a satisfactory model is produced (https://swissmodel.expasy.org/). 6. UniLectin [95]: It is an interactive, publicly accessible platform that provides curated and predicted lectin data, not only including

• ://github.com/BojarLab/LectinOracle). 4. CAPSIF [109]: CArbohydrate-Protein Site IdentiFier is a convolutional neural network able to predict protein–carbohydrate binding interface from a protein structure. In contrast to other DN algorithms, as GlyNet and LectinOracle, which predict lectin-carbohydrate binding

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• antibiotic-sparing anti-infective drugs. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins have shown promising results. Light-sensitive lectin ligands could allow the modulation of lectins activity with precise spatiotemporal control. Despite the potential of

• photoswitchable tools, few photochromic lectin ligands have been developed. We have designed and synthesized several O- and S-galactosyl azobenzenes as photoswitchable ligands of LecA and evaluated their binding affinity with isothermal titration calorimetry. We show that the synthesized monovalent glycoligands

• due to stronger unfavorable entropy, they are in general of lower affinity. The validation of this proof-of-concept and the dissection of thermodynamics of binding will help for the further development of lectin ligands that can be controlled by light. Keywords: carbohydrates; glycosyl azobenzenes

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• garnered attention for their roles as laboratory probes and potential therapeutics. Here, we report the discovery and characterization of Cucumis melo agglutinin (CMA1), a new R-type lectin from melon. Our findings reveal CMA1’s unique glycan-binding profile, mechanistically explained by its 3D structure

• ), which we contrasted with the established R-type lectin Ricinus communis agglutinin 1 (RCA1). We also report binding of specific glycosaminoglycan subtypes and a general enhancement of binding by sulfation. Further validation using agglutination, thermal shift assays, and surface plasmon resonance

• groundwork for further exploration of its biological and therapeutic potential. Keywords: carbohydrate; glycan array; melon; plant lectin; R-type; Introduction Lectins have long been the subject of intense scientific scrutiny, serving as molecular bridges that span the realms of biochemistry, cellular

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• project with groups from Universities in Munich and Pennsylvania we are investigating carbohydrate–lectin interactions using programmable glycodendrimersomes based on synthetic glycans. We have earlier synthesized 2-[2-(2-azidoethoxy)ethoxy]ethyl (TEG-N3) glycosides of lactose, 3’-Su-lactose and LacdiNAc

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• paper by Mehta et al. [5], who summarize recent developments and available online resources for glycan array data, a very powerful technique for understanding the structural element(s) of glycans required for different lectin binding. This further emphasizes the role of glycans as mediators of cellular

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• more likely to survive internalization by lung epithelial cells [147][154][155]. Although DHN-melanin is generally associated with immune evasion it was recently found to be recognized in higher animals via the C-type lectin receptor (MelLec) which interacts with the naphthalene-diol domain of DHN

• -melanin. Additionally, the surfactant protein D (SP-D), a soluble C-type lectin receptor (CLR), is also able to recognise DHN-melanin and opsonize it to increase the immune response. However, MelLec receptors are only present on some endothelial and myeloid cells [156][157]. Fumigaclavines Fumigaclavine C

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• in studying the HIV-inactivating lectin cyanovirin-N protein as a model system (S52CCV-N). Single fluorine atoms were introduced at the 4-, 5-, 6- or 7-positions of Trp49 and the 4-position of Phe4, Phe54, and Phe80 (Figure 8). Simultaneously, the paramagnetic nitroxide spin label was chemically

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• representations. We believe the utility of these wild-cards extends beyond biosynthesis modeling (Table 9) and may be useful in the description of glycan-chemosynthetic procedures, lectin identification of glycan motifs, and any other purpose where a group of glycans (rather than an individual glycan) is being

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• sulfonato-calix[4]arene binding to Ralstonia solanacearum lectin that was chemically dimethylated on three lysine residues and the N-terminus was studied by 15N-HSQC titrations [50][51]. Both ligands prefer binding to methylated lysines whereby the binding affinity (for the free amino acids) increases with

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• , all concentration plots, and a model structure. The software was designed to be useful for lectin and enzyme analysis. It has been used to discover fine specificities of lectins (AAL, SNA) and glycosidase enzymes (α1-2-fucosidase and an α2-3,6,8-neuraminidase) [45]. 3. SignalFinder-Microarray: Status

• shown the utility of CCARL on lectin data extensively. CCARL, however, does not currently have a web or GUI interface making it only possible to use it programmatically. Like other automated methods, however, the authors accept that the parameters of this method would need to be fine-tuned depending on

• to experiments. Many arrays can be printed on a single slide, termed sub-arrays. The slides can then be used in a glycan microarray experiment where they are incubated with a glycan binding protein (GBP), such as lectin, antibody, or serum, virus, etc., followed by addition of a detection reagent, if

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• of the N-glycan and its structural dynamics, therefore its selective recognition by lectin receptors and antibodies. The atomistic-level of detail information that the MD simulations provide us with, highlights that the effects of different functionalizations, in terms of monosaccharide types and

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• Information File 1) of galectin-1, a β-sheet lectin protein that is available in bovine spleen [53] (for a detailed crystal structure see the Protein Data Bank; PDB ID 1SLT). Given the amphiphilic and pH-responsive nature of PEP-1, we investigated both the pH- and concentration-dependent formation of

• (Glu−) amino acids [73][74]. Mechanistic insights into the observed conformational transformation via molecular dynamics simulations are underway in our laboratory. Conclusion In summary, we synthesized a naturally occurring amphiphilic peptide fragment, PEP-1, from a β-sheet lectin protein, galectin-1

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• cell lines, endowing our hybrid sensor with specific cell target ability [35]. The cytoselectivity of the Glyco-DTE reporter was firstly checked in PBS buffer through lectin binding experiments. The lectin used here, peanut agglutinin (PNA), can selectively bind with β-ᴅ-galactoside that mimics the

• role of ASGPr on HepG2 cell membranes [36][37]. As shown in Figure S4 (Supporting Information File 1), the addition of PNA to the solution of Glyco-DTE resulted in a fluorescence enhancement with an obvious spectral blue-shift, while the addition of another lectin, conconavalin A (Con A), did not cause

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• cytosolic or endosomal PRRs. PRRs are classified into: Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs) and C-type lectin receptors (CLRs) [4]. Muramyl dipeptide (MDP, N-acetylmuramyl-ʟ-alanyl-ᴅ-isoglutamine) is the smallest peptidoglycan fragment (Figure 1) capable of

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• between the equatorial sugar hydroxy groups and the receptor NH residues and also in the CH···π interactions with the hydrophobic anthrylene sidewalls. This combination of noncovalent interactions closely mimics the sugar-binding behavior exhibited by lectin proteins. The Davis group has explored more

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• was measured by competitive enzyme-linked lectin assays. One of the synthetic compounds presenting two GlcNAc units showed the highest inhibitory effect of this study with an IC50 of 11 µM corresponding to a 3182-fold improvement compared to GlcNAc. These synthetic molecules were used to produce giant

• solution inevitably cause the disruption of the supramolecular assembly [23]. Analyses under saline stress were not performed as the ultimate aim is to use of those OMV models under physiological conditions. Biological evaluation of the synthesized compounds Competitive enzyme-linked lectin assays (ELLA

• ) were used to evaluate the binding properties of compounds 5 and 8 towards wheat germ agglutinin (WGA), a lectin from Triticum vulgaris that is specific for N-acetylneuraminic acid and N-acetylglucosamine. This assay consists in measuring the ability of the compounds to inhibit the binding of WGA

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• identified based on the primary amino acid sequence alone, due to the presence of conserved lectin-associated domains (carbohydrate-recognition domains; CRDs) [27]. Well known lectin examples within the innate immune system include the DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC

• -SIGN) [28][29], the dendritic cell-specific C-type lectins (Dectin-1, Dectin-2) [30][31], the macrophage inducible C-type lectin (Mincle) [32][33][34], the macrophage C-type lectin (MCL) [35][36], and the mannose receptor (MR) [37][38] (Figure 1). Since the importance of host lectins in Mtb infection

• -galactopyranosides, L-fucopyranosides and sialic acids) that comprise the most terminal, and therefore most accessible for lectin recognition, oligosaccharide regions contribute to a vast diversity of possible glycocalyx structures [40][41][42]. It is known, for example, that the carbohydrate composition of the

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• and invade bladder and kidney tissue, and to promote biofilm formation. Bladder-adhesive FimH is a mannose-specific lectin and the kidney-adhesive PapG binds galactosides. In a second indication, FimH also mediates the attachment of E. coli to the gut, inducing inflammation in Crohn’s disease [13

• . Therefore, multivalent display of lectin and ligand results in a higher avidity [22][23]. The Lindhorst group also synthesized and analyzed so-called glycoclusters, e.g., 7 (Figure 1), where the saccharide moiety is displayed in a multivalent fashion [17][24][25][26]. When this simple trimannosylated

• compound was tested in a whole cell ELISA, it was shown that the apparent binding affinity increases by a factor of 250 versus methyl α-D-mannoside, while the valency only increased by a factor three. It should be noted that the full length FimH adhesin consists of two domains, a lectin and a pilin domain

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• ligand–receptor interactions in solution. We have employed an interdisciplinary methodology to achieve facile photolabeling of the lectin FimH, which is a bacterial protein, crucial for adhesion, colonization and infection. Following our earlier work, we have here designed and synthesized diazirine

• accuracy. We are concluding from this study that photolabeling of FimH with sugar diazirines has only very limited success and cannot be regarded a facile approach for covalent modification of FimH. Keywords: diazirines; docking; FimH; lectin ligands; mannosides; mass spectrometry; photoaffinity labelling

• photolabeling studies [7][8]. Over several years it has been our goal, to exploit diazirine-labeled mannopyranosides for protein labeling. In the course of this work, we have gradually improved our target design and synthetic procedures [9][10][11] with the aim to eventually address the bacterial lectin FimH

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• favoured an aggregation mechanism for inhibition [55] whereas matching the valency has previously been assumed to lead to the formation of 1:1 complexes [59][60][61][62][63][64]. They found that the potency exhibited by compound 33 in the usual enzyme-linked lectin assay (IC50 = 260 ± 20 pM) was slightly

• lower that for the tetravalent compound 22b (IC50 = 160 ± 40 pM) [56]. Inhibition results described in this review are essentially all derived from very similar types of enzyme-linked lectin assays (ELLA) in which the inhibitors are used to prevent CTB-linked horseradish peroxidase from binding to

• inhibitors 22b and 33 were re-evaluated using this new assay, they were found to be even more active than previously measured in the ELLA (IC50 = 34 pM for 22b in organoid assay vs 160 pM in ELLA; IC50 = 15 pM for 33 in organoid assay vs 260 pM in ELLA). While enzyme-linked lectin assays will undoubtedly

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• -specific, dimeric lectin LcA (Lens culinaris lectin), these GAuNPs underwent aggregation. The GAuNP aggregates that were formed were then used as a supramolecular glycoprobe for the rapid detection of α-fetoprotein (AFP)-L3, a protein which binds strongly to LcA and is a serological biomarker for

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• Christoph P. Sager Deniz Eris Martin Smiesko Rachel Hevey Beat Ernst Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland 10.3762/bjoc.13.255 Abstract In general, carbohydrate–lectin interactions are characterized by high specificity but

• carbohydrate–lectin interactions of the innate immune system but also in bacterial adhesion, a process key for the bacterium’s survival. In an effort to better understand the particular characteristics, which contribute to a successful carbohydrate recognition domain, the mannose-binding sites of six C-type

• mammalian mannose-binding sites are in general flat and solvent exposed, the half-lives of carbohydrate–lectin complexes are rather short since water molecules can easily access and displace the ligand from the binding site. In contrast, the bacterial lectin FimH benefits from a deep mannose-binding site

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• modifications. Transporters and proteins purely involved in recognition (lectin, antibodies, carbohydrate binding modules, glycosaminoglycan binding proteins) are the other important classes of carbohydrate-binding proteins. Figure 7 shows the evolution of the number of carbohydrate interacting proteins that

• processes is well documented, as in the case of embryogenesis, fertilization, inflammation and metastasis. Lectins play a key role in parasite-symbiotic recognition in microbes and invertebrates of plants and vertebrates. The present role assigned to lectin lies in their ability to decipher sugar-encoded

• therefore accessible to solvent. One or two calcium ions, identified in several lectin families of different origins, are involved in the carbohydrate binding by direct coordination to the sugar hydroxy groups. The comparison of detailed conformational features of oligosaccharides and their modes of

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• colloidal solution color. Therefore, several biosensors for the detection of proteins [42], lectin [25][27][43], cancer biomarkers [28] and viruses [44][45] were developed. Photoluminescence properties of ultrasmall gold nanoclusters and nanodots have been exploited to detect Escherichia coli (a bacteria

• , fertility, etc. [75][76][77]. Lectins are the most diffused class of proteins which recognize carbohydrate ligands and they are widely studied to develop systems able to detect lectin–carbohydrate interactions. Yan et al. exploited the use of gold nanoparticles to recognize and differentiate lectins by

• efforts, the GAuNPs showed an incremented lectin identification power, at low protein concentrations, enabling an easy tool for sugar–lectin recognition. The glycan–protein interaction has been studied as well employing surface-enhanced Raman spectroscopy (SERS) exploiting AuNP ability in amplifying Raman