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

• a specific glycoform. For example, if we consider the 3D structure of the β(1-2)-Xyl Man3 glycoblock vs the Man3 without Xyl, we can understand how the β(1-2)-Xyl position within that unit negates binding to DC-SIGN lectins [19], see Supporting Information File 1, Figure S3 panels a and b

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

• pili on the cell surface (discussed further below). C-Type lectin C-Type lectins are one of the largest and most diverse lectin families, including the Mtb-recognizing eukaryotic host immune receptors DC-SIGN, Dectin-1/2, Mincle, MCL, and MR, mentioned before. These lectins bind carbohydrates in a

• Abbreviations AG: arabinogalactan; ALS: agglutinin-like sequences; D-Araf: D-arabinofuranoside; CpnT: outer membrane channel protein; CRD: carbohydrate-recognition domain; DC-SIGN: dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin; dectin: dendritic cell-specific C-type lectin; FHA

• 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

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

• ) [19][20], pulmonary surfactant-associated protein D (SP-D) [21], dendritic cell-specific ICAM-3-grabbing non-integrins 1 and 2 (DC-SIGN, also known as CD209; and DC-SIGNR, also known as CD299) [22][23], and mannose-binding protein (MBP) [24]. These CLECs exert their function through different

• mechanisms, for instance by pathogen internalization as in the case of BDCA-2 and langerin, by pathogen opsonization as mediated by SP-D and MBP, or by T-cell interactions as mediated by DC-SIGN and DC-SIGNR [25][26]. In contrast, pathogens have developed numerous adhesins that mediate their interaction with

• ]. Crystal structures of mannose–lectin complexes The X-ray structures of six mannose-binding receptors in complex with either α-D-mannose (1) or methyl α-D-mannopyranoside (2) were analyzed (Figure 1 and Table 1, A–C and G–I). Since for DC-SIGNR (Figure 1, D) and DC-SIGN (Figure 1, E) neither complexes with

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

• system in response to pathogens mediated by lectins, like DC-SIGN. Mammalian cell surface lectins, expressed on the surface of dendritic cells (DC) and macrophages, recognize in a multivalent way a vast array of glycans on the exterior of pathogens. Natural carbohydrate ligands include high-mannose N

• -inflammatory response in dendritic cells via interaction with the lectin DC-SIGN, as indicated by the up-regulation of several maturation markers and increased secretion of pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) [97]. These data indicate that a multivalent system of

• -SIGN targeting through GAuNPs has also been exploited differently in a study on GAuNPs functionalized with α-fucosylamide, an efficacious synthetic DC-SIGN ligand, analogue of the natural fucose-containing Lewisx trisaccharide [98]. This paper shows that GAuNPs bearing 50% of fucosylamide are able to

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• affinity for the antibody thus demonstrating a clear synergy in the interaction of the templated fragments (see Figure 3 for selected examples). This approach was subsequently scaled out to optimize the affinity of DC-SIGN ligands using a library of PNA-tagged glycans that included unnatural modifications

• in the glycans. DC-SIGN is a tetrameric lectin implicated in interactions with a broad array of pathogens including HIV. A library of 37,485 assemblies was prepared by hybridization of two sets of PNA-tagged glycoconjugates onto a library of DNA templates (Figure 4). Screening the library by affinity

• selection against immobilized DC-SIGN and analysis of the best-fit sample by PCR amplification/sequence analysis of the template led to the discovery of an assembly with a 30-fold enhancement in binding over the unmodified mannose assembly [44]. Importantly, following PCR amplification of the template, the

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• related to HIV envelope [18]. GNPs coated with oligomannosides of the gp120 (manno-GNPs) were able to inhibit the DC-SIGN-mediated HIV-1 trans-infection of human T-cells [19] and gold glyconanoparticles coated with sulfated ligands showed to interfere with the adhesion/fusion of HIV during its entry [20

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• expression and MHCII. Furthermore, DCs activated by the glycodendron 5 stimulate T lymphocytes to proliferate in a mixed lymphocytes reaction (MLR). Keywords: cancer immunotherapy; DC-SIGN; DC targeting; glycodendron; GM3-lactone mimetic; multivalent glycosystems; multivalent interactions; Introduction

• , dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), which belongs to the class of CLRs, is expressed mainly on the surface of immature DCs and plays a crucial role in the uptake of specific pathogens. DC-SIGN is able to bind in a Ca2+-dependent manner mannose and fucose residues on highly

• ]. Therefore, a combination of DC-SIGN ligands and specific tumor-associated antigens could successfully target DCs and trigger an efficient antitumor response. Melanoma has long been considered a promising target for immunotherapeutic approaches and has been a major focus of clinical development efforts in

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• hydrophilic than simple sugars. We have been developing pseudo-disaccharide molecules such as 23 [32] (Scheme 7) as mimics of mannose disaccharides for the interaction with DC-SIGN and other C-lectins [33][34][35]. This molecule and its derivatives [36] contain lipophilic moieties that generally increase

• 24 is a mimic for DC-SIGN inhibition and its bioactivity will be tested elsewhere. Inhibition studies The inhibitory potency of 22 for LecA was studied in an ELISA type assay by using a glycochip as the solid phase [10]. In this assay an IC50 value of 0.9 μM was determined (Table 1). This compared

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• dendritic cell specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN) [8]. Thus, while total syntheses of many PIM structures have now been reported, the synthesis of substructures remains a worthwhile endeavor as these are useful to clarify fine details of enzymatic substrate recognition

• , following immobilization on glass slides, their binding to the lectin DC-SIGN was assessed [31]. Significant questions remain in the area of PIM/LM/LAM biosynthesis that could be assisted by suitable well-defined mannan substructures. For example, the identity of the α-1,2-mannosyltransferase(s) involved in