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

• posttranslational modifications of peptides in proteomics can be adapted to specifically identify glycopeptides. What is also obvious for glycobioinformatics is that it needs an own language that is understood by both computers and researchers to facilitate the exchange of glyco-specific information as well as the

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• oligosaccharides and glycopeptides under basic aqueous conditions [32][33]. Nevertheless, most of the conventional conditions for glycosyl fluoride activation have considerable drawbacks in terms of atom efficiency and environmental impact. These methods generally require (1) stoichiometric amounts of promoters

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• developed to facilitate and improve both the identification and quantification of glycopeptides. Here, a selection of these tools was combined and evaluated with the aim of establishing a robust glycopeptide detection and quantification workflow targeting enriched glycoproteins. For this purpose, a tryptic

• aided by the Byonic software. Additional MS1-based glycopeptide identification relying on accurate mass and retention time differences using GlycopeptideGraphMS considerably expanded the set of confidently annotated glycopeptides. For glycopeptide quantification, the performance of LaCyTools was

• automated processing of several IgA glycopeptides. Finally, this study presents a semiautomated workflow for reliable glycoproteomic data analysis by the combination of software packages for MS/MS- and MS1-based glycopeptide identification as well as the integration of analyte quality control and

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

• rule can be extended to glycopeptides providing a means of representing glycans directly embedded in a glycopeptide. “PEP(Gal[3S]b3(GNb6)AN)TIDE” would describe a trisaccharide O-glycan bound to the threonine of an eponymously named glycoprotein. Overall, the consensus in these representations centers

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• form of images [13][14]. Besides, these tools for representing glycans in 2D and 3D shape [15] allowed the integration of glycans into protein structures or complexes. The tools developed in the last few years have automated the sketching of glycans and glycopeptides, allowing rapid display of

• ://www.virtualglycome.org/DrawGlycan. The same web page gives access to a downloadable, standalone Graphical User Interface (GUI) version of this tool with additional functionality. It can be launched from different platforms including Windows, Mac or Linux. The program can be used to render glycans and glycopeptides using

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• proteomic sample preparation and protease digestion, coupled with depletion of abundant proteins or enrichment of glycopeptides to enable their measurement. There have also been several advances in glycopeptide quantification strategies including chemical labelling, label-free and data-independent

• use a predefined list of analytes and masses to interrogate MS1 data, and I-GPA [20], GlycopeptideGraphMS [21], GlycoFragwork [22], and GlycReSoft [23], which integrate identification and abundance/intensity information for glycopeptides (a recent review is provided in [10]). Importantly, the

• Fisher) and Byonic (Protein Metrics), to extract occupancy and glycoform abundancy of all identified glycopeptides from LC–MS/MS datasets. We applied the workflow to a published dataset comparing the plasma glycoproteomes of liver cancer patients (heptatocellular carcinoma, HCC) and healthy controls [20

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• containing glycopeptides were prepared in solution. The applicability of two common peptide coupling reagents, using an orthogonal Fmoc/t-Bu strategy along with acetyl protecting groups for the carbohydrate moiety, was studied. Thus, the prepared libraries of glycopeptides were designed as model systems of

• cell surfaces for future investigations by combined preparative mass spectroscopy and scanning tunneling microscopy (STM) using soft-landing electrospray beam deposition (ES-IBD), on metal surfaces. Keywords: amino acids; asparagine; carbohydrates; glycopeptides; peptidomimetics; Introduction

• Glycopeptides are generally found on virtually every eukaryotic and prokaryotic cell surface. So far, the study of glycopeptide interactions with other proteins gave some insight into important biological functions, for instance, intracellular communication, cell–cell recognition, immune response, and

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

• peptides were prepared and characterized. In their structures, all glycopeptides comprised of mannose and the key pharmacophore – desmuramyl peptide. These moieties are connected through a glycolyl or hydroxyisobutyryl linker and additionally modified on N/C terminus with an adamantane subunit. The

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• , Department of Chemistry, Bielefeld University, Universitätsstraße 25, Bielefeld, D-33615, Germany 10.3762/bjoc.15.162 Abstract Antifreeze glycoproteins are a class of biological agents which enable living at temperatures below the freezing point of the body fluids. Antifreeze glycopeptides usually consist

• of repeating tripeptide unit (-Ala-Ala-Thr*-), glycosylated at the threonine side chain. However, on the microscopic level, the mechanism of action of these compounds remains unclear. As previous research has shown, antifreeze activity of antifreeze glycopeptides strongly relies on the overall

• have shown a strong influence of the stereochemistry of amino acid residues on the peptide chain stability, which could be connected to the antifreeze activity of these compounds. A better understanding of the mechanism of action of antifreeze glycopeptides would allow applying these materials, e.g

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• molecular recognition, cell–cell interaction, immunological recognition and transmission of biological information [4][5][6]. They are easily transformed into important bioactive compounds such as oligosaccharides, glycopeptides, nucleosides, antibiotics, uronic acids and other natural products [1][2][3

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• ], disaccharides or higher oligosaccharides [5][6] as well as multivalent [7][8] carbohydrate units have been developed. These glycomimetics and glycopeptides have also found applications as bioactive compounds [9][10]. One group of the scaffolds includes iminosugars [11][12] as analogues of the monosaccharides

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• with N-glycan oxazolines, have become the biocatalysts of choice for the convergent production of a wide variety of biologically interesting glycopeptides and for the remodelling of glycoproteins, including mAbs [33][34]. The efficient production of N-glycan oxazolines as donor substrates for these

• purification was achieved by SEC (Sephadex G-15). Commercially available chicken ovalbumin can be used as a source of high mannose N-glycans, from which glycopeptides can be obtained by pronase digestion [108]. A mixture of free truncated glycans (Man5GlcNAc and Man6GlcNAc) can then be released [109] by the

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• ][25], and thurandacin [26] revealed S-glycosylation of cysteines. Carbohydrates bound to these bacteriocins are glucose or N-acetylglucosamine. For two of these glycopeptides, the corresponding S-GTs have been characterized and their versatility for a wide range of sugar donors has been tested [26][27

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• using the same one-pot strategy [78]. In a follow up work by Novoa et al. [79] by using NEt3 and DMC, S-linked glycopeptides at cysteine residues on a solid phase could also be obtained. This methodology or very similar variations thereof is now being utilized by several laboratories for various

• glycopeptides (the alkyne source was propargylglycine in the peptide sequence) which have potential in synthetic vaccines [87][88] in moderate yields (30–47%) [85]. Once again these conditions take place under mild wet conditions, further underscoring the potential of this method. Due to the mild nature of DMC

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• determine the coalescence temperature which resulted in calculated rotation barriers of 17.9–18.3 kcal/mol for the rotamers. Keywords: amino acids; carbohydrates; glycoconjugates; glycopeptides; N-(2-aminoethyl)glycine; Introduction The glycocalyx is a fringy or fuzzy polysaccharide layer coating most

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• high multivalent effects towards jack-bean α-mannosidase were reported for fullerene- [11], cyclodextrin- [12][13] and porphyrin- [14] based scaffolds decorated with 1-deoxynojirimycin (DNJ) or 1-deoxymannojirimycin as the bioactive iminosugars. Self-assembled DNJ-based glycopeptides also experienced a

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• spiro [42] 2-oxazolines [43] are limited, to the best of our knowledge. With our interest in the area of glycopeptides [44] and carbohydrates [45], and owing to the importance of ribosides in general and spiroribofuranoses [46] in particular for drug discovery, in this paper, we report the synthesis of

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• glycopeptides [6], glycosaminoglycans [7][8][9], and chains as long as 30-mers [10]. Key to automated assembly is the identification of reliable monosaccharide building blocks to construct particular linkages. To date, α-(2,3)- and α-(2,6)-sialylated glycans have been accessible by automation only via

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• comprising 4’-fluoro-6TF-antigen-MUC1 glycopeptides and BSA or TTox proteins as immunological carriers. The fluorinated MUC1 glycopeptide-TTox conjugate 18b was successfully applied to immunizations of mice leading to strong tolerance-breaking immune responses and the production of selective IgG antibodies

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• acids; aniline; carbohydrates; glycoconjugates; glycopeptides; Introduction Glycans or other complex oligosaccharide structures, present on the surface of every prokaryotic and eukaryotic cell, are important for a large number of biological recognition processes like, for example, intercellular

• interactions. Recently our group has prepared a series of trifunctional glycopeptide building blocks with aliphatic backbones, which allow for the automated construction of combinatorial libraries of highly divers glycopeptides suitable for studying carbohydrate–protein interactions [5][6][7][8]. Hitherto, our

• libraries with an aromatic backbone based on 3-aminomethyl-5-aminobenzoic acid to which the sugar moieties are attached through a malonyl linker. For that purpose we designed the two building blocks 1 and 2 (Figure 1) which both can be converted into the respective glycopeptides using standard Fmoc

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• assembling glycopeptides demonstrated an antiviral potency which was up to 50 times higher than the activity of peptide-free glycans. Keywords: glycopeptides; influenza virus; multivalent glycosystems; oligoglycine; polyglycine II; self-assembling; tectomers; Introduction Recently, we have synthesized and

• , the reaction was carried out in a saturated aqueous solution of lithium bromide, which prevented the formation of hydrogen bonds and thus increased the solubility of oligoglycines. Glycopeptides were isolated from the reaction mixture by gel-permeation chromatography (yields 70–75%). The peptide

• modification by the amino group with mono- or oligosaccharides dramatically increased their solubility in water. This may support their antiviral action (see below), because glycopeptides act topically, in the respiratory tract, and are administered as a spray. We then investigated the ability of synthesized

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• and glycopeptides are the key constituents of the cellular membrane and extracellular matrix, and play a pivotal role in various key cellular events such as cell–cell recognition, host–pathogen or host–symbiont interactions, molecular recognition of antibodies and metastasis [1][2][3][4][5]. The

• ][27][28][29][30][31]. The α-GalNAc-linked glycopeptides, α-N-glycosidically linked to the polypeptide chain through the amido nitrogen of an asparagine residue at the N-terminal [32], were found to be the most important semi-synthetic glycoconjugates, usually modified from their naturally occurring

• few examples of oligosaccharides and glycopeptides mimics have so far been prepared by a click chemistry strategy [40][41][42][43][44][45][46][47][48]. Most recently, we developed a strategy for the synthesis of 3-amino-2,3-dideoxysugars using a regio- and stereoselective tandem hydroamination

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• potential of defined sugar presentation on a template. The β-glycopeptides are synthetically accessible by incorporation of sugar amino acids in β-peptide helical secondary structures, whereas sugar-β-amino acids were derived from a continuation of our efforts in synthesis of sugar-amino acids [51][52]. β3

• was chosen as C-terminal amino acid. Further the C-glycosidic attachment of the sugar units at the peptide backbone was varied with respect to the configuration. As evident from CD spectroscopy, out of eight β-glycopeptides 1–8 (Figure 2), the five β-glycopeptides 2–6 were shown to adopt a 314-helix

• literature protocol [49]. Synthesis of β-glycopeptides 1–8 Fmoc-protected sugar β-amino acids 12a–d were found to be compatible with SPPS conditions. Therefore, the sugar units were introduced in the β-peptide like regular amino acids using a modified Fmoc SPPS protocol on mild acid sensitive Sieber amide

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• obtained the α-C-glycosides in an efficient manner, we explored their synthetic utility to synthesize a 2-deoxy-2-amino-α-C-glycoside. 2-Deoxy-2-amino-α-C-glycosides have received considerable attention in recent years due to their use in the synthesis of glycopeptides [50][51], glycolipids [51] and

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• support mimic peptides, the degree of aggregation of peptide chains during solid-phase synthesis is decreased, which facilitates the synthesis of peptides and glycopeptides [33]. Since amides are incompatible with many organic reactions, pure PEG resins, such as SPOCC [34], ChemMatrix [35] or NovaPEG