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

• mammalian glycans rely on a group of “only” 10 monosaccharide units, they can be assembled, in linear or branched chains, through different glycosidic linkages and diverse spatial orientations, which can also undergo modifications, such as methylation, sulfation, and phosphorylation, resulting in a plethora

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• broad pH range between 5.0 and 9.0 and was highly expressed in Pichia pastoris [79]. Carrageenase Carrageenans are sulfated saccharide polymers with a wide range of commercial applications. The differential sulfation patterns allow for carrageenans to be differentiated into three basic forms – κ-, ι

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• -vertebrates contain numerous “unusual” and remarkable structural features such as methylation, sulfation, and zwitterionic non-sugar substituents, again glucuronic acid and often unusual architectures such as substituted core-fucose just as an example [44][52]. While the methylated moss glycans are accessible

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

• ), 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

• site. Lastly, we note that both CSC and CSA contain sulfated GalNAc, which, together with the observation of GalNAc6Sβ1-4GlcNAc as one of the highest binders on the NCFG array, leads us to speculate that sulfation further enhances CMA1 binding, a pattern that has been observed for several lectins [28

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

• glycosylation reactions. The 3’-sulfate was finally introduced through tin activation in benzene/DMF followed by treatment with a sulfur trioxide–trimethylamine complex in a 66% yield. Keywords: regioselective sulfation; thioglycoside donors; Thomsen–Friedenreich antigen; Introduction In a collaboration

• 10 furnished target 1 in a 90% yield. Formation of a stannylidene acetal via tin-activation was employed to achieve selective 3’-O-sulfation of compound 1 [27], with a variety of conditions being attempted (Table 1). With a TEG-N3 lactose compound, tin-activation was performed with Bu2SnO in

• refluxing MeOH, followed by stirring with SO3·NMe3 in 1,4-dioxane to afford the 3’-O-sulfate in 65% yield [1]. Here, however, this choice of solvent in the sulfation step led to the material being insoluble and no reaction was observable by TLC. Changing the solvent of the sulfation reaction to DMF resulted

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• proteins. The structural and functional heterogeneities of GAGs as well as their ability to bind specific proteins are determined by the sugar composition of the GAG, the size of the GAG chains, and the degree and pattern of sulfation. A deep understanding of the interactions in protein–GAG complexes is

• proteins or nucleic acids, GAGs are constantly altered by processing enzymes and thus they vary greatly in molecular mass, disaccharide unit composition, and sulfation. Based on their core structure they are categorized into six different classes, viz. heparan sulfate (HS), heparin (HP), hyaluronic acid

• (HA), chondroitin sulfate (CS), dermatan sulfate (DS), and keratan sulfate (KS). The structural and functional diversities of GAGs are regulated by their sequence, size of the chains, degree of sulfation, and the ability to bind proteins [1][18][19][20][21]. This structural diversity of GAGs

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• for the addition of GalNAc to glucuronic acid to increase chondroitin polymer length, CHST3, CHST11, and UST are involved in the sulfation of GalNAc and iduronic acid, and DSEL is the epimerase which converts glucuronic acid to iduronic acid in CS/DS chains. MECP2 disproportionately regulates heparan

• CSGALNACT2, which is preferred for synthesizing disaccharide repeats. CHSY1, CHSY3, CHPF, and CHPF2 all exhibit dual β1-3GlcAT and β1-4GlcAT activity. Additional enzymes mediate sulfation. Epimerization of glucuronic acid to iduronic acid by DSE and DSEL results in the conversion of chondroitin sulfates to

• are critical for heparin sulfate function include the HS2/3/6ST sulfotransferases, the GlcA epimerase GLCE, and additional enzymes mediating N-sulfation (i.e., NDSTs). 11) Hyaluronan synthesis: This pathway consists of the three hyaluronan synthases, HAS1–3. 12) Glycophosphatidylinositol (GPI) anchor

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• modification of monosaccharides, for example through sulfation, acetylation or phosphorylation, which follow the same pattern as decoration. Glycologue structure identifiers order branches by linkage position, writing the branch with the lowest linkage first, reading from right to left. Modifiers are written

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

• ). MS + “ [ ” + modification + “ ] ” is used to denote the modification. For example, “G[2S]” describes sulfation on the second carbon of a ᴅ-glucopyranose. The anomericity is expressed to the right of the modification (i.e., “G[2S]a”). Multiple modifications to the same MS are ordered based on the

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• escape the host immune response [1][7]. These polysaccharides of SP consist of repeating units (RU) that range from di- to heptasaccharides that may be branched and/or charged [8]. Modifications such as O-acetylation, phosphorylation, and sulfation further increase CPS complexity. Many bacterial

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• . Lomonosov Moscow State University, Moscow, 119991, Russia 10.3762/bjoc.15.63 Abstract The studies on the recently discovered pyranoside-into-furanoside rearrangement have led us to conformational investigations of furanosides upon their total sulfation. Experimental NMR data showed that in some cases

• gauche-orientation upon sulfation. The effect is less pronounced in the galactosides. For all the studied structures changes in the conformational distribution were revealed by quantum mechanical calculations, that explained the observed changes in intraring coupling constants occurring upon introduction

• of sulfates. Keywords: ab initio calculations; conformational analysis; furanosides; NMR; sulfation; Introduction Changes in the conformations of monosaccharides expectedly accompany their modification with different functional groups. Thus, spatial repulsion of silyl groups results in inversion or

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• ][6][7][8]. For example, Jacquinet, Lopin-Bon and co-workers presented the preparation of CS oligomers with different sulfation motifs, starting from a single GlcA-GalNAc disaccharide precursor easily obtained by depolymerization of the natural product [9][10][11][12][13]. CS tetrasaccharides

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• large circulatory reservoir catalyzed by steroid sulfatase (STS), is one of the major alternative sources of prehormone estrone for the local supply of estrogens [2]. The availability of free estrone on the cellular level depends on the expression of STS and/or SULT, which catalyze the sulfation of the

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• lipophilicity, for instance through sulfation [18], silylation or esterification [19] of the aliphatic hydroxy and phenolic groups found in lignin. Chemical esterification of lignin [19][20][21] or its model compounds [22], using acetic anhydride in organic solvents such as DCM or pyridine have previously been

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

• of the later, many sources of structural micro-heterogeneities occur as the epimerization at the C-5 position of uronic acids, and N- and O-sulfation. Of paramount interest is the elucidation of the role of GAGs in their interactions with such important proteins as extracellular matrix proteins

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• Schotten–Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz 1H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the

• ; multivalency; selectins; sulfation; Introduction In a series of publications [1][2][3][4][5][6] our group reported on the syntheses of carbohydrate mimetics [7][8][9][10][11] that are based on aminopyrans, aminooxepanes or other aminopolyols. These compounds and their conjugates were prepared to be examined

• reasonably reproducible procedure. Since other sulfation methods such as SO3∙pyridine [35] provided unsatisfactory results an excess of SO3∙DMF [13][36] was used as sulfating agent and the resulting sulfuric acid monoesters (in a mixture with an excess of the sulfating reagent) were directly converted into

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• well as to the closely connected O-sulfation reactions. Finally, a brief comparison will be made between the acidic O-acylation techniques, treated so far, with other available methodologies for chemoselective O-acylation, some of which have emerged recently. Chemoselective O-acylation of amino

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• applications in medicinal chemistry, e.g., as selectin inhibitors. After O-sulfation the biological activity of these divalent compounds will be studied together with that of related carbohydrate mimetics. Experimental For general methods: See Supporting Information File 1 Approach to divalent carbohydrate

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• natural product conjugates. Keywords: glycosylation; masked mycotoxins; resorcylic acid esters; sulfation; zearalenone; Introduction Resorcylic acid lactones (RALs, Figure 1), a compound class of benzannulated macrolides, are pharmacologically active secondary metabolites produced by a variety of

• -glucoside than ZEN-14-glucoside in barley roots [17]. We therefore intended to develop a synthetic method for regiocontrolled conjugation of ZEN. Basically, the RAL type moiety of ZEN contains two possible sites for glycosylation/sulfation, but due to the higher reactivity of the phenol group at position 14

• protection of the more nucleophilic 4’-phenol and subsequent glucosylation or sulfation should lead to the desired products. For the development of a reliable protective group strategy and subsequent reaction optimization, 2,4-dihydroxybenzoic acid isopropyl ester (9) [29] was used as a RAL mimic. For

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

• such as sulfation or phosphorylation, as well as non-native features for biological experiments, such as linkers for glycoconjugation. This results in a high requirement concerning the chemical stability of the linker and solid support. Orthogonal linker 1 (Scheme 2) was designed to address these

• necessitates aqueous solutions to perform Staudinger reductions in the placement of amino groups as well as for ester saponification used to remove temporary protective groups prior to sulfation. A range of different glycosylation conditions were explored, whereby the couplings were performed either twice by

• resin, granting access to the reactive sites on the solid support. The azide reduction can be used as a key step to facilitate N-sulfation, which is necessary in the synthesis of heparin [48], or for the introduction of prevalent N-acetates. In summary, we demonstrate that PS-based resins perform best

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• reaction conditions on solid support since cleavage only occurs following preactivation. Thus, different modification reactions, such as Staudinger reduction, ester saponification or sulfation, necessary for the synthesis of GAGs, can be performed on solid support in an automated carbohydrate synthesizer

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• (particle diameter 6 nm). After sulfation of the hydroxyl groups the multivalent conjugates obtained displayed strong binding to P- and L-selectins, thus demonstrating that compounds such as 24 and 28 are of interest for the development of new anti-inflammatory agents [27][28]. Inspired by these first

An efficient partial synthesis of 4′-O-methylquercetin via regioselective protection and alkylation of quercetin

• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang,
• Jian-Ping Yang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2009, 5, No. 60, doi:10.3762/bjoc.5.60

• modifications of the phenolic hydroxyl groups: methylation, sulfation and glucuronidation [2]. Plasma analysis of pigs fed with quercetin-rich diets show that quercetin is absent and only methylated metabolites such as 4′-O-methylquercetin (2, tamarixetin) and 3′-O-methylquercetin (3, isorhamnetin, Figure 1