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5. Chemoenzymatic Synthesis of Tri‐antennary N‐Glycans Terminating in Sialyl‐Lewisx Reveals the Importance of Glycan Complexity for Influenza A Virus Receptor Binding.

Author

Li, Tiehai, Spruit, Cindy M., Wei, Na, Liu, Lin, Wolfert, Margreet A., de Vries, Robert P., and Boons, Geert‐Jan

Subjects
INFLUENZA A virus, INFLUENZA viruses, GLYCAN structure, VIRUS diseases, EGG yolk, FARNESOID X receptor
Abstract

Sialyl‐Lewisx (SLex) is involved in immune regulation, human fertilization, cancer, and bacterial and viral diseases. The influence of the complex glycan structures, which can present SLex epitopes, on binding is largely unknown. We report here a chemoenzymatic strategy for the preparation of a panel of twenty‐two isomeric asymmetrical tri‐antennary N‐glycans presenting SLex‐Lex epitopes on either the MGAT4 or MGAT5 arm that include putative high‐affinity ligands for E‐selectin. The N‐glycans were prepared starting from a sialoglycopeptide isolated from egg yolk powder and took advantage of inherent substrate preferences of glycosyltransferases and the use of 5′‐diphospho‐N‐trifluoracetylglucosamine (UDP‐GlcNHTFA) that can be transferred by branching N‐acetylglucosaminyltransferases to give, after base treatment, GlcNH2‐containing glycans that temporarily disable an antenna from enzymatic modification. Glycan microarray binding studies showed that E‐selectin bound equally well to linear glycans and tri‐antennary N‐glycans presenting SLex‐Lex. On the other hand, it was found that hemagglutinins (HA) of H5 influenza A viruses (IAV) preferentially bound the tri‐antennary N‐glycans. Furthermore, several H5 HAs preferentially bound to N‐glycan presenting SLex on the MGAT4 arm. SLex is displayed in the respiratory tract of several avian species, demonstrating the relevance of investigating the binding of, among others IAVs, to complex N‐glycans presenting SLex. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Structure‐Based Design and Synthesis of Lipid A Derivatives to Modulate Cytokine Responses.

Author

Verpalen, Enrico C. J. M., Brouwer, Arwin J., Wolfert, Margreet A., and Boons, Geert‐Jan

Subjects
TOLL-like receptor agonists, LIPID synthesis, IMMUNOMODULATORS, ESCHERICHIA coli, IMMUNOLOGICAL adjuvants, GLYCERYL ethers, LIPIDS, ETHER lipids
Abstract

Agonists of Toll like receptors (TLRs) have attracted interest as adjuvants and immune modulators. A crystal structure of TLR4/MD2 with E. coli LPS indicates that the fatty acid at C‐2 of the lipid A component of LPS induces dimerization of two TLR4‐MD2 complexes, which in turn initiates cell signaling leading to the production of (pro)inflammatory cytokines. To probe the importance of the (R)‐3‐hydroxymyristate at C‐2 of lipid A, a range of bis‐ and mono‐phosphoryl lipid A derivatives with different modifications at C‐2 were prepared by a strategy in which 2‐methylnaphthyl ethers were employed as permanent protecting group that could be readily removed by catalytic hydrogenation. The C‐2 amine was protected as 9‐fluorenylmethyloxycarbamate, which at a later stage could be removed to give a free amine that was modified by different fatty acids. LPS and the synthetic lipid As induced the same cytokines, however, large differences in activity were observed. A compound having a hexanoyl moiety at C‐2 still showed agonistic properties, but further shortening to a butanoyl abolished activity. The modifications had a larger influence on monophosphoryl lipid As. The lipid As having a butanoyl moiety at C‐2 could selectively antagonize TRIF associated cytokines induced by LPS or lipid A. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Synthetic HNK-1 containing glycans provide insight into binding properties of serum antibodies from MAG-neuropathy patients

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Bunyatov, Mehman, Wolfert, Margreet A., Huizinga, Ruth, Schreurs, Marco W.J., Jacobs, Bart C., Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Bunyatov, Mehman, Wolfert, Margreet A., Huizinga, Ruth, Schreurs, Marco W.J., Jacobs, Bart C., and Boons, Geert-Jan

Published
2022

12. Antibacterial and anti-inflammatory properties of host defense peptides against Staphylococcus aureus

Author

Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Cecotto, Leonardo, van Kessel, Kok, Wolfert, Margreet A, Vogely, Charles, van der Wal, Bart, Weinans, Harrie, van Strijp, Jos, Amin Yavari, Saber, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Cecotto, Leonardo, van Kessel, Kok, Wolfert, Margreet A, Vogely, Charles, van der Wal, Bart, Weinans, Harrie, van Strijp, Jos, and Amin Yavari, Saber

Published
2022

13. Antibacterial and anti-inflammatory properties of host defense peptides against Staphylococcus aureus

Author

Cecotto, Leonardo (author), van Kessel, Kok (author), Wolfert, Margreet A. (author), Vogely, Charles (author), van der Wal, Bart (author), Weinans, Harrie (author), van Strijp, Jos (author), Amin Yavari, S. (author), Cecotto, Leonardo (author), van Kessel, Kok (author), Wolfert, Margreet A. (author), Vogely, Charles (author), van der Wal, Bart (author), Weinans, Harrie (author), van Strijp, Jos (author), and Amin Yavari, S. (author)

Abstract

Cationic host defense peptides (HDPs) are a promising alternative to antibiotics in the fight against Staphylococcus aureus infections. In this study, we investigated the antibacterial and immunomodulatory properties of three HDPs namely IDR-1018, CATH-2, and LL-37. Although all three HDPs significantly inhibited LPS-induced activation of human macrophages, only CATH-2 prevented S. aureus growth. When applied to different infection models focused on intracellularly surviving bacteria, only IDR-1018 showed a consistent reduction in macrophage bacterial uptake. However, this observation did not correlate with an increase in killing the efficiency of intracellular S. aureus. Here, we conclude that despite the promising antibacterial and anti-inflammatory properties of the selected HDPs, macrophages’ intrinsic antibacterial functions were not improved. Future studies should either focus on combining different HDPs or using them synergistically with other antibacterial agents to improve immune cells’ efficacy against S. aureus pathogenesis., Biomaterials & Tissue Biomechanics

Published
2022
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18. Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2

Author

Liu, Lin, Chopra, Pradeep, Li, Xiuru, Bouwman, Kim M, Tompkins, S Mark, Wolfert, Margreet A, de Vries, Robert P, Boons, Geert-Jan, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, and Sub Chemical Biology and Drug Discovery

Subjects
Microarray, Chemistry(all), General Chemical Engineering, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Epitope, Virus, Cell membrane, 03 medical and health sciences, chemistry.chemical_compound, Sulfation, 0302 clinical medicine, medicine, QD1-999, 030304 developmental biology, Coronavirus, chemistry.chemical_classification, 0303 health sciences, biology, 010405 organic chemistry, General Chemistry, Heparan sulfate, Heparin, Oligosaccharide, HEXA, 0104 chemical sciences, 3. Good health, Cell biology, Chemistry, medicine.anatomical_structure, Enzyme, Proteoglycan, chemistry, 030220 oncology & carcinogenesis, biology.protein, Chemical Engineering(all), Research Article, medicine.drug
Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments, using an extensive heparan sulfate (HS) oligosaccharide library, showed that the receptor binding domain (RBD) of the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. A hexasaccharide composed of IdoA2S-GlcNS6S repeating units was identified as the minimal binding epitope. Surface plasmon resonance showed the SARS-CoV-2 spike protein binds with a much higher affinity to heparin (KD = 55 nM) compared to the RBD (KD = 1 μM) alone. It was also found that heparin does not interfere in angiotensin-converting enzyme 2 (ACE2) binding or proteolytic processing of the spike. However, exogenous administered heparin or a highly sulfated HS oligosaccharide inhibited RBD binding to cells. Furthermore, an enzymatic removal of HS proteoglycan from physiological relevant tissue resulted in a loss of RBD binding. The data support a model in which HS functions as the point of initial attachment allowing the virus to travel through the glycocalyx by low-affinity high-avidity interactions to reach the cell membrane, where it can engage with ACE2 for cell entry. Microarray binding experiments showed that ACE2 and HS can simultaneously engage with the RBD, and it is likely no dissociation between HS and RBD is required for binding to ACE2. The results highlight the potential of using HS oligosaccharides as a starting material for therapeutic agent development., Various methods demonstrate that the RBD of SARS-CoV-2 spike can bind to heparan sulfate (HS) in a sequence-dependent manner supporting a model in which HS functions as the initial attachment point.

Published
2021

19. Heparan sulfate proteoglycans as attachment factor for SARS-CoV-2

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Liu, Lin, Chopra, Pradeep, Li, Xiuru, Bouwman, Kim M., Tompkins, S. Mark, Wolfert, Margreet A., Vries, Robert P. de, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Liu, Lin, Chopra, Pradeep, Li, Xiuru, Bouwman, Kim M., Tompkins, S. Mark, Wolfert, Margreet A., Vries, Robert P. de, and Boons, Geert-Jan

Published
2021

20. The 3-O-sulfation of heparan sulfate modulates protein binding and lyase degradation

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Chopra, Pradeep, Joshi, Apoorva, Wu, Jiandong, Lu, Weigang, Yadavalli, Tejabhiram, Wolfert, Margreet A, Shukla, Deepak, Zaia, Joseph, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Chopra, Pradeep, Joshi, Apoorva, Wu, Jiandong, Lu, Weigang, Yadavalli, Tejabhiram, Wolfert, Margreet A, Shukla, Deepak, Zaia, Joseph, and Boons, Geert-Jan

Published
2021

21. Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2

Author

Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Liu, Lin, Chopra, Pradeep, Li, Xiuru, Bouwman, Kim M, Tompkins, S Mark, Wolfert, Margreet A, de Vries, Robert P, Boons, Geert-Jan, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Liu, Lin, Chopra, Pradeep, Li, Xiuru, Bouwman, Kim M, Tompkins, S Mark, Wolfert, Margreet A, de Vries, Robert P, and Boons, Geert-Jan

Published
2021

22. Mono- and Di-Fucosylated Glycans of the Parasitic Worm S. mansoni are Recognized Differently by the Innate Immune Receptor DC-SIGN

Author

Srivastava, Apoorva D, Unione, Luca, Wolfert, Margreet A, Valverde, Pablo, Arda, Ana, Jiménez-Barbero, Jesús, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, and European Commission

Subjects
Glycan, Glycosylation, binding, mechanism, Receptors, Cell Surface, ligand, 010402 general chemistry, 01 natural sciences, Catalysis, Epitope, glycomics, NMR spectroscopy, fucose, Polysaccharides, antigens, Animals, Humans, Lectins, C-Type, Avidity, Binding site, chemistry.chemical_classification, Innate immune system, immune modulation, Full Paper, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, structural basis, Schistosoma mansoni, General Chemistry, Full Papers, biology.organism_classification, Immunity, Innate, 3. Good health, 0104 chemical sciences, DC-SIGN, C-type Lectins, Biochemistry, biology.protein, glycans, affinity, Glycans | Hot Paper, molecular recognition, Glycoprotein, Cell Adhesion Molecules, reveals, chemical synthesis
Abstract

The parasitic worm, Schistosoma mansoni, expresses unusual fucosylated glycans in a stage‐dependent manner that can be recognized by the human innate immune receptor DC‐SIGN, thereby shaping host immune responses. We have developed a synthetic approach for mono‐ and bis‐fucosylated LacdiNAc (LDN‐F and LDN‐DF, respectively), which are epitopes expressed on glycolipids and glycoproteins of S. mansoni. It is based on the use of monosaccharide building blocks having carefully selected amino‐protecting groups, facilitating high yielding and stereoselective glycosylations. The molecular interaction between the synthetic glycans and DC‐SIGN was studied by NMR and molecular modeling, which demonstrated that the α1,3‐fucoside of LDN‐F can coordinate with the Ca2+‐ion of the canonical binding site of DC‐SIGN allowing for additional interactions with the underlying LDN backbone. The 1,2‐fucoside of LDN‐DF can be complexed in a similar manner, however, in this binding mode GlcNAc and GalNAc of the LDN backbone are placed away from the protein surface resulting in a substantially lower binding affinity. Glycan microarray binding studies showed that the avidity and selectivity of binding is greatly enhanced when the glycans are presented multivalently, and in this format Lex and LDN‐F gave strong responsiveness, whereas no binding was detected for LDN‐DF. The data indicates that S. mansoni has developed a strategy to avoid detection by DC‐SIGN in a stage‐dependent manner by the addition of a fucoside to a number of its ligands., Chemically synthesized oligosaccharides derived from the parasite worm S. mansoni made it possible to investigate by a combination of analytical techniques molecular interactions with the innate immune receptor DC‐SIGN. It showed that by further fucosylation of antigens such as LDN‐NF, detection by DC‐SIGN is prevented, which in turn may be important for shaping immune responses during different phases of the life cycle of the parasite.

Published
2020

24. SARS-CoV-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner

Author

Liu, Lin, Chopra, Pradeep, Li, Xiuru, Wolfert, Margreet A., Tompkins, S. Mark, and Boons, Geert-Jan

Subjects
Article
Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments using an extensive heparan sulfate (HS) oligosaccharide library showed the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. Hexa- and octasaccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with higher affinity to heparin (K D 55 nM) compared to the receptor binding domain (RBD, K D 1 µM) alone. An octasaccharide composed of IdoA2S-GlcNS6S could inhibit spike-heparin interaction with an IC 50 of 38 nM. Our data supports a model in which the RBD of the spike of SARS-CoV-2 confers sequence specificity for HS expressed by target cells whereas an additional HS binding site in the S1/S2 proteolytic cleavage site enhances the avidity of binding. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.

Published
2020
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25. Chemoenzymatic Synthesis of Campylobacter jejuni Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities

Author

Li, Tiehai, Wolfert, Margreet A, Wei, Na, Huizinga, Ruth, Jacobs, Bart C, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Immunology, Neurology, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, and Chemical Biology and Drug Discovery

Subjects
Ganglioside, Microarray, biology, Guillain-Barre syndrome, Chemistry, General Chemistry, 010402 general chemistry, biology.organism_classification, medicine.disease, 01 natural sciences, Biochemistry, Campylobacter jejuni, Catalysis, Epitope, 0104 chemical sciences, Microbiology, Colloid and Surface Chemistry, Campylobacter Jejuni Infection, medicine, biology.protein, Antibody, Polyneuropathy
Abstract

Guillain-Barré syndrome is often caused by Campylobacter jejuni infection that has induced antibodies to the lipo-oligosaccharide (LOS) that cross-react with gangliosides at peripheral nerves causing polyneuropathy. To examine fine specificities of anti-ganglioside antibodies and develop a more robust platform for diagnosis and disease monitoring, we developed a chemoenzymatic approach that provided an unprecedented panel of oligosaccharides composed of the inner-core of the LOS of C. jejuni extended by various ganglioside mimics. The compounds and corresponding ganglio-oligosaccharides were printed as a microarray to examine binding specificities of lectins, anti-ganglioside antibodies, and serum antibodies of GBS patients. Although lectins and anti-ganglioside antibodies did not differentiate the ganglio-oligosaccharides and mimics, the patient serum samples bound much more strongly to the ganglioside mimics. The data indicate that antibodies have been elicited to a foreign epitope that includes a heptosyl residue unique of bacterial LOS and that these antibodies subsequently cross-react with lower affinity to gangliosides. The microarray detected anti-GM1a antibodies with high sensitivity and will be attractive for diagnosis, disease monitoring, and immunological research.

Published
2020

26. Modulation of innate immune responses with synthetic lipid A derivatives

Author

Yanghui Zhang, Gaekwad, Jidnyasa, Wolfert, Margreet A., and Boons, Geert-Jan

Subjects
Lipids -- Structure, Lipids -- Chemical properties, Polysaccharides -- Chemical properties, Sugars -- Chemical properties, Chemistry
Abstract

A synthetic approach is developed for providing easy access to a wide range of lipid A's by using a common disaccharide building block functionalized with a versatile set of protecting groups. The results have shown that cytokine secretion induced by lipopolysaccharides (LPS) and lipid A is complex, which can be utilized for the development of immuno-modulating therapies.

Published
2007

27. Mono and Di-Fucosylated Glycans of the Parasitic Worm S. Mansoniare Recognized Differently by the Innate Immune Receptor DC-SIGN

Author

Química orgánica II, Kimika organikoa II, Srivastava, Apoorva D., Unione, Luca, Wolfert, Margreet A., Valverde, Pablo, Ardá, Ana, Jiménez Barbero, Jesús, Boons, Geert-Jan, Química orgánica II, Kimika organikoa II, Srivastava, Apoorva D., Unione, Luca, Wolfert, Margreet A., Valverde, Pablo, Ardá, Ana, Jiménez Barbero, Jesús, and Boons, Geert-Jan

Abstract

The parasitic worm,Schistosoma mansoni, expresses unusual fucosylated glycans in a stage-dependent manner that can be recognized by the human innate immune receptor DC-SIGN, thereby shaping host immune responses. We have developed a synthetic approach for mono- and bis-fucosylated LacdiNAc (LDN-F and LDN-DF, respectively), which are epitopes expressed on glycolipids and glycoproteins ofS. mansoni. It is based on the use of monosaccharide building blocks having carefully selected amino-protecting groups, facilitating high yielding and stereoselective glycosylations. The molecular interaction between the synthetic glycans and DC-SIGN was studied by NMR and molecular modeling, which demonstrated that the alpha 1,3-fucoside of LDN-F can coordinate with the Ca2+-ion of the canonical binding site of DC-SIGN allowing for additional interactions with the underlying LDN backbone. The 1,2-fucoside of LDN-DF can be complexed in a similar manner, however, in this binding mode GlcNAc and GalNAc of the LDN backbone are placed away from the protein surface resulting in a substantially lower binding affinity. Glycan microarray binding studies showed that the avidity and selectivity of binding is greatly enhanced when the glycans are presented multivalently, and in this format Le(x)and LDN-F gave strong responsiveness, whereas no binding was detected for LDN-DF. The data indicates thatS. mansonihas developed a strategy to avoid detection by DC-SIGN in a stage-dependent manner by the addition of a fucoside to a number of its ligands.

Published
2020

28. Mutation of the second sialic acid-binding of influenza A virus neuraminidase drives compensatory mutations in hemagglutinin

Author

Du, Wenjuan, Wolfert, Margreet A., Peeters, B.P.H., Kuppeveld, Frank J.M., van, Boons, Geert-Jan, Vries, Erik, de, Haan, Cornelis A.M., de, Du, Wenjuan, Wolfert, Margreet A., Peeters, B.P.H., Kuppeveld, Frank J.M., van, Boons, Geert-Jan, Vries, Erik, de, and Haan, Cornelis A.M., de

Abstract

Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics. Most pandemics occurred upon adaptation of avian IAVs to humans. This adaptation includes a hallmark receptor-binding specificity switch of hemagglutinin (HA) from avian-type α2,3- to human-type α2,6-linked sialic acids. Complementary changes of the receptor-destroying neuraminidase (NA) are considered to restore the precarious, but poorly described, HA-NA-receptor balance required for virus fitness. In comparison to the detailed functional description of adaptive mutations in HA, little is known about the functional consequences of mutations in NA in relation to their effect on the HA-NA balance and host tropism. An understudied feature of NA is the presence of a second sialic acid-binding site (2SBS) in avian IAVs and absence of a 2SBS in human IAVs, which affects NA catalytic activity. Here we demonstrate that mutation of the 2SBS of avian IAV H5N1 disturbs the HA-NA balance. Passaging of a 2SBS-negative H5N1 virus on MDCK cells selected for progeny with a restored HA-NA balance. These viruses obtained mutations in NA that restored a functional 2SBS and/or in HA that reduced binding of avian-type receptors. Importantly, a particular HA mutation also resulted in increased binding of human-type receptors. Phylogenetic analyses of avian IAVs show that also in the field, mutations in the 2SBS precede mutations in HA that reduce binding of avian-type receptors and increase binding of human-type receptors. Thus, 2SBS mutations in NA can drive acquisition of mutations in HA that not only restore the HA-NA balance, but may also confer increased zoonotic potential.

Published
2020

29. Chemoenzymatic Synthesis of Campylobacter jejuni Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Li, Tiehai, Wolfert, Margreet A, Wei, Na, Huizinga, Ruth, Jacobs, Bart C, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Li, Tiehai, Wolfert, Margreet A, Wei, Na, Huizinga, Ruth, Jacobs, Bart C, and Boons, Geert-Jan

Published
2020

30. Mono- and Di-Fucosylated Glycans of the Parasitic Worm S. mansoni are Recognized Differently by the Innate Immune Receptor DC-SIGN

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Srivastava, Apoorva D, Unione, Luca, Wolfert, Margreet A, Valverde, Pablo, Arda, Ana, Jiménez-Barbero, Jesús, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Srivastava, Apoorva D, Unione, Luca, Wolfert, Margreet A, Valverde, Pablo, Arda, Ana, Jiménez-Barbero, Jesús, and Boons, Geert-Jan

Published
2020

31. Mutation of the second sialic acid-binding site of influenza A virus neuraminidase drives compensatory mutations in hemagglutinin

Author

Virologie, Afd Chemical Biology and Drug Discovery, dI&I I&I-1, Sub Chemical Biology and Drug Discovery, Du, Wenjuan, Wolfert, Margreet A, Peeters, Ben, van Kuppeveld, Frank J M, Boons, Geert-Jan, de Vries, Erik, de Haan, Cornelis A M, Virologie, Afd Chemical Biology and Drug Discovery, dI&I I&I-1, Sub Chemical Biology and Drug Discovery, Du, Wenjuan, Wolfert, Margreet A, Peeters, Ben, van Kuppeveld, Frank J M, Boons, Geert-Jan, de Vries, Erik, and de Haan, Cornelis A M

Published
2020

32. Heparan sulfate proteoglycans as attachment factor for SARS-CoV-2

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Liu, Lin, Chopra, Pradeep, Li, Xiuru, Wolfert, Margreet A, Tompkins, S Mark, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Liu, Lin, Chopra, Pradeep, Li, Xiuru, Wolfert, Margreet A, Tompkins, S Mark, and Boons, Geert-Jan

Published
2020

33. Chemoenzymatic Synthesis of Campylobacter jejuni Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities

Author

Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Li, Tiehai, Wolfert, Margreet A, Wei, Na, Huizinga, Ruth, Jacobs, Bart C, Boons, Geert-Jan, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Li, Tiehai, Wolfert, Margreet A, Wei, Na, Huizinga, Ruth, Jacobs, Bart C, and Boons, Geert-Jan

Published
2020

35. Synthesis and biological evaluation of Rhizobium sin-1 lipid A derivatives

Author

Demchenko, Alexei V., Wolfert, Margreet A., Santhanam, Balaji, Moore, James N., and Boons, Geert-Jan

Subjects
Glycosylation -- Methods, Rhizobium -- Chemical properties, Sugars -- Research, Chemistry
Abstract

A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. A key aspect of the synthetic strategy was a chemoselective glycosylation of a selenoglycosyl donor with a thioglycosyl acceptor to give selectively protected disaccharide.

Published
2003

38. Protecting Group-Controlled Enzymatic Glycosylation of Oligo-N-Acetyllactosamine Derivatives

Author

Boons, Geert-Jan, Gagarinov, Ivan A, Li, Tiehai, Wei, Na, Sastre Toraño, Javier, de Vries, Robert P, Wolfert, Margreet A, Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, and Chemical Biology and Drug Discovery

Abstract

We describe a chemoenzymatic strategy that can give a library of differentially fucosylated and sialylated oligosaccharides starting from a single chemically synthesized tri-N-acetyllactosamine derivative. The common precursor could easily be converted into 6 different hexasaccharides in which the glucosamine moieties are either acetylated (GlcNAc) or modified as a free amine (GlcNH2) or Boc (GlcNHBoc). Fucosylation of the resulting compounds by a recombinant fucosyl transferase resulted in only modification of the natural GlcNAc moieties providing access to 6 selectively mono- and bis-fucosylated oligosaccharides. Conversion of the GlcNH2 or GlcNHBoc moieties into the natural GlcNAc followed by sialylation by sialyl transferases gave 12 differently fucosylated and sialylated compounds. The oligosaccharides were printed as a microarray which was probed by several glycan binding proteins demonstrating that complex patterns of fucosylation can modulate glycan recognition.

Published
2019

39. Chemoenzymatic synthesis of the oligosaccharide moiety of the tumor-associated antigen disialosyl globopentaosylceramide

Author

't Hart, Ingrid M E, Li, Tiehai, Wolfert, Margreet A, Wang, Shuo, Moremen, Kelley W, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, and Chemical Biology and Drug Discovery

Abstract

Disialosyl globopentaosylceramide (DSGb5) is often expressed by renal cell carcinomas. To investigate properties of DSGb5, we have prepared its oligosaccharide moiety by chemically synthesizing Gb5 which was enzymatically sialylated using the mammalian sialyltransferases ST3Gal1 and ST6GalNAc5. Glycan microarray binding studies indicate that Siglec-7 does not recognize DSGb5, and preferentially binds Neu5Acα(2,8)Neu5Ac containing glycans.

Published
2019

40. Protecting Group-Controlled Enzymatic Glycosylation of Oligo-N-Acetyllactosamine Derivatives

Author

Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Boons, Geert-Jan, Gagarinov, Ivan A, Li, Tiehai, Wei, Na, Sastre Toraño, Javier, de Vries, Robert P, Wolfert, Margreet A, Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Boons, Geert-Jan, Gagarinov, Ivan A, Li, Tiehai, Wei, Na, Sastre Toraño, Javier, de Vries, Robert P, and Wolfert, Margreet A

Published
2019

41. Chemoenzymatic synthesis of the oligosaccharide moiety of the tumor-associated antigen disialosyl globopentaosylceramide

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, 't Hart, Ingrid M E, Li, Tiehai, Wolfert, Margreet A, Wang, Shuo, Moremen, Kelley W, Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, 't Hart, Ingrid M E, Li, Tiehai, Wolfert, Margreet A, Wang, Shuo, Moremen, Kelley W, and Boons, Geert-Jan

Published
2019

42. N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses

Author

Afd Chemical Biology and Drug Discovery, dPB I&I, LS Pathologie, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Broszeit, Frederik, Tzarum, Netanel, Zhu, Xueyong, Nemanichvili, Nikoloz, Eggink, Dirk, Leenders, Tim, Li, Zeshi, Liu, Lin, Wolfert, Margreet A, Papanikolaou, Andreas, Martínez-Romero, Carles, Gagarinov, Ivan A, Yu, Wenli, García-Sastre, Adolfo, Wennekes, Tom, Okamatsu, Masatoshi, Verheije, Monique H, Wilson, Ian A, Boons, Geert-Jan, de Vries, Robert P, Afd Chemical Biology and Drug Discovery, dPB I&I, LS Pathologie, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Broszeit, Frederik, Tzarum, Netanel, Zhu, Xueyong, Nemanichvili, Nikoloz, Eggink, Dirk, Leenders, Tim, Li, Zeshi, Liu, Lin, Wolfert, Margreet A, Papanikolaou, Andreas, Martínez-Romero, Carles, Gagarinov, Ivan A, Yu, Wenli, García-Sastre, Adolfo, Wennekes, Tom, Okamatsu, Masatoshi, Verheije, Monique H, Wilson, Ian A, Boons, Geert-Jan, and de Vries, Robert P

Published
2019

43. Protecting Group-Controlled Enzymatic Glycosylation of Oligo-N-Acetyllactosamine Derivatives

Author

Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Boons, Geert-Jan, Gagarinov, Ivan A, Li, Tiehai, Wei, Na, Sastre Toraño, Javier, de Vries, Robert P, Wolfert, Margreet A, Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Boons, Geert-Jan, Gagarinov, Ivan A, Li, Tiehai, Wei, Na, Sastre Toraño, Javier, de Vries, Robert P, and Wolfert, Margreet A

Published
2019

44. N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses

Author

Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, FAH GZ pluimvee, dPB I&I, LS Pathologie, Sub Chemical Biology and Drug Discovery, Broszeit, Frederik, Tzarum, Netanel, Zhu, Xueyong, Nemanichvili, Nikoloz, Eggink, Dirk, Leenders, Tim, Li, Zeshi, Liu, Lin, Wolfert, Margreet A, Papanikolaou, Andreas, Martínez-Romero, Carles, Gagarinov, Ivan A, Yu, Wenli, García-Sastre, Adolfo, Wennekes, Tom, Okamatsu, Masatoshi, Verheije, Monique H, Wilson, Ian A, Boons, Geert-Jan, de Vries, Robert P, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, FAH GZ pluimvee, dPB I&I, LS Pathologie, Sub Chemical Biology and Drug Discovery, Broszeit, Frederik, Tzarum, Netanel, Zhu, Xueyong, Nemanichvili, Nikoloz, Eggink, Dirk, Leenders, Tim, Li, Zeshi, Liu, Lin, Wolfert, Margreet A, Papanikolaou, Andreas, Martínez-Romero, Carles, Gagarinov, Ivan A, Yu, Wenli, García-Sastre, Adolfo, Wennekes, Tom, Okamatsu, Masatoshi, Verheije, Monique H, Wilson, Ian A, Boons, Geert-Jan, and de Vries, Robert P

Published
2019

46. Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide

Author

Supekar, Nitin T., Lakshminarayanan, Vani, Capicciotti, Chantelle J., Sirohiwal, Anju, Madsen, Cathy S, Wolfert, Margreet A, Cohen, Peter A., Gendler, Sandra J., Boons, Geert-Jan, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, and Chemical Biology and Drug Discovery

Abstract

A fully synthetic MUC1-based cancer vaccine has been designed and chemically synthesized that contains an endogenous helper T-epitope (MHC class II epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC). It also activated cytotoxic T-lymphocytes and collectively the immunological data demonstrate engagement of helper T-cells in immune activation. A synthetic methodology was developed for a penta-glycosylated MUC1 glycopeptide and anti-sera of mice immunized by the new vaccine recognized such a structure. Previous reported fully synthetic MUC-1 based cancer vaccines that elicited potent immune responses employed exogenous helper T-epitopes derived from microbes. It is the expectation that the use of the newly identified endogenous helper T-epitope will be more attractive because it will activate cognate CD4+ T-cells that will provide critical tumor-specific help intra-tumorally during the effector stage of tumor rejection and will aid in the generation of sustained immunological memory.

Published
2018

48. N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses

Author

Broszeit, Frederik, primary, Tzarum, Netanel, additional, Zhu, Xueyong, additional, Nemanichvili, Nikoloz, additional, Eggink, Dirk, additional, Leenders, Tim, additional, Li, Zeshi, additional, Liu, Lin, additional, Wolfert, Margreet A., additional, Papanikolaou, Andreas, additional, Martínez-Romero, Carles, additional, Gagarinov, Ivan A., additional, Yu, Wenli, additional, García-Sastre, Adolfo, additional, Wennekes, Tom, additional, Okamatsu, Masatoshi, additional, Verheije, Monique H., additional, Wilson, Ian A., additional, Boons, Geert-Jan, additional, and de Vries, Robert P., additional

Published
2019
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50. Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including α-actinin 4

Author

Akimoto Yoshihiro, Miura Yuri, Toda Tosifusa, Wolfert Margreet A, Wells Lance, Boons Geert-Jan, Hart Gerald W, Endo Tamao, and Kawakami Hayato

Subjects
O-GlcNAc modification, Hexosamine biosynthetic pathway, Kidney, Glomerulus, Cytoskeleton, α-actinin, GK Rat, Mass spectrometry, Proximity Ligation Assay, Medicine
Abstract

Abstract Purpose The objective of the present study is to identify proteins that change in the extent of the modification with O-linked N-acetylglucosamine (O-GlcNAcylation) in the kidney from diabetic model Goto-Kakizaki (GK) rats, and to discuss the relation between O-GlcNAcylation and the pathological condition in diabetes. Methods O-GlcNAcylated proteins were identified by two-dimensional gel electrophoresis, immunoblotting and peptide mass fingerprinting. The level of O-GlcNAcylation of these proteins was examined by immunoprecipitation, immunoblotting and in situ Proximity Ligation Assay (PLA). Results O-GlcNAcylated proteins that changed significantly in the degree of O-GlcNAcylation were identified as cytoskeletal proteins (α-actin, α-tubulin, α-actinin 4, myosin) and mitochondrial proteins (ATP synthase β, pyruvate carboxylase). The extent of O-GlcNAcylation of the above proteins increased in the diabetic kidney. Immunofluorescence and in situ PLA studies revealed that the levels of O-GlcNAcylation of actin, α-actinin 4 and myosin were significantly increased in the glomerulus and the proximal tubule of the diabetic kidney. Immunoelectron microscopy revealed that immunolabeling of α-actinin 4 is disturbed and increased in the foot process of podocytes of glomerulus and in the microvilli of proximal tubules. Conclusion These results suggest that changes in the O-GlcNAcylation of cytoskeletal proteins are closely associated with the morphological changes in the podocyte foot processes in the glomerulus and in microvilli of proximal tubules in the diabetic kidney. This is the first report to show that α-actinin 4 is O-GlcNAcylated. α-Actinin 4 will be a good marker protein to examine the relation between O-GlcNAcylation and diabetic nephropathy.

Published
2011
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