ORCID Profile
0000-0003-3111-5954
Current Organisations
University of Georgia
,
Universiteit Utrecht
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Publisher: American Chemical Society (ACS)
Date: 02-06-2021
Publisher: Proceedings of the National Academy of Sciences
Date: 13-01-2021
Abstract: Although heparan sulfate (HS) modified by a 3- O -sulfate (3-OS) has been implicated in many biological processes, there is only a rudimentary understanding of ligand requirements of HS-binding proteins requiring this type of modification. We developed a modular synthetic approach that provided a structurally erse collection of HS oligosaccharides with and without 3-OS. The compounds were printed as a glycan microarray to determine ligand requirements of HS-binding proteins, which revealed specific HS sequons for binding, and led to the discovery of proteins needing 3-OS for binding. The compounds made it possible to determine receptor requirements of herpes simplex virus, and substrate specificities of heparin lyases. The platform provides an important means to examine the biology of 3-OS−modified HS.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-07-2020
DOI: 10.1126/SCISIGNAL.AAX6313
Abstract: Evolutionarily conserved cysteine residues mediate the sensitivity of the metabolic kinase FN3K to shifts in redox status.
Publisher: American Chemical Society (ACS)
Date: 14-10-2020
Publisher: Cold Spring Harbor Laboratory
Date: 10-05-2020
DOI: 10.1101/2020.05.10.087288
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. Hexa- and octa-saccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with much higher affinity to heparin (K D = 55 nM) compared to the RBD (K D = 1 μM) alone. We also found that heparin does not interfere in angiotensin-converting enzyme 2 (ACE2) binding or proteolytic processing of the spike. Our data supports a model in which HS functions as the point of initial attachment for SARS-CoV-2 infection. Tissue staining studies using biologically relevant tissues indicate that heparan sulfate proteoglycan (HSPG) is a critical attachment factor for the virus. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.
Publisher: Elsevier BV
Date: 07-2018
Publisher: American Chemical Society (ACS)
Date: 19-08-2019
Publisher: Elsevier BV
Date: 2013
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-12-2021
Abstract: This study provides proof of concept for cell-based heparin without heparin-induced thrombocytopenia side effects.
Publisher: American Chemical Society (ACS)
Date: 16-06-2022
Abstract: Three-dimensional (3D) synthetic heparan sulfate (HS) constructs possess promising attributes for neural tissue engineering applications. However, their sulfation-dependent ability to facilitate molecular recognition and cell signaling has not yet been investigated. We hypothesized that fully sulfated synthetic HS constructs (bearing compound
Publisher: Springer Science and Business Media LLC
Date: 20-03-2020
DOI: 10.1038/S41467-020-15284-Y
Abstract: Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a “ S hotgun” I on M obility M ass S pectrometry S equencing (SIMMS 2 ) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3 O -sulfate groups. SIMMS 2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS 2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation.
Publisher: Cold Spring Harbor Laboratory
Date: 06-02-2022
DOI: 10.1101/2022.02.05.22270494
Abstract: During the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics. We analyzed historical influenza virus epidemiological data from 2003-2019 to assess the historical frequency of near-absence of seasonal influenza virus circulation and its impact on the size and severity of subsequent epidemics. Additionally, we measured haemagglutination inhibition-based antibody titres against seasonal influenza viruses using longitudinal serum s les from 165 healthy adults, collected before and during the COVID-19 pandemic, and estimated how antibody titres against seasonal influenza waned during the first two years of the pandemic. Low country-level prevalence of influenza virus (sub)types over one or more years occurred frequently before the COVID-19 pandemic and had relatively small impacts on subsequent epidemic size and severity. Additionally, antibody titres against seasonal influenza viruses waned negligibly during the first two years of the pandemic. The commonly held notion that lulls in influenza virus circulation, as observed during the COVID-19 pandemic, will lead to larger and/or more severe subsequent epidemics might not be fully warranted, and it is likely that post-lull seasons will be similar in size and severity to pre-lull seasons. European Research Council, Netherlands Organization for Scientific Research, Royal Dutch Academy of Sciences, Public Health Service of Amsterdam. During the first years of the COVID-19 pandemic, the incidence of seasonal influenza was unusually low, leading to widespread concerns of exceptionally large and/or severe influenza epidemics in the coming years. We searched PubMed and Google Scholar using a combination of search terms (i.e., “seasonal influenza”, “SARS-CoV-2”, “COVID-19”, “low incidence”, “waning rates”, “immune protection”) and critically considered published articles and preprints that studied or reviewed the low incidence of seasonal influenza viruses since the start of the COVID-19 pandemic and its potential impact on future seasonal influenza epidemics. We found a substantial body of work describing how influenza virus circulation was reduced during the COVID-19 pandemic, and a number of studies projecting the size of future epidemics, each positing that post-pandemic epidemics are likely to be larger than those observed pre-pandemic. However, it remains unclear to what extent the assumed relationship between accumulated susceptibility and subsequent epidemic size holds, and it remains unknown to what extent antibody levels have waned during the COVID-19 pandemic. Both are potentially crucial for accurate prediction of post-pandemic epidemic sizes. We find that the relationship between epidemic size and severity and the magnitude of circulation in the preceding season(s) is decidedly more complex than assumed, with the magnitude of influenza circulation in preceding seasons having only limited effects on subsequent epidemic size and severity. Rather, epidemic size and severity are dominated by season-specific effects unrelated to the magnitude of circulation in the preceding season(s). Similarly, we find that antibody levels waned only modestly during the COVID-19 pandemic. The lack of changes observed in the patterns of measured antibody titres against seasonal influenza viruses in adults and nearly two decades of epidemiological data suggest that post-pandemic epidemic sizes will likely be similar to those observed pre-pandemic, and challenge the commonly held notion that the widespread concern that the near-absence of seasonal influenza virus circulation during the COVID-19 pandemic, or potential future lulls, are likely to result in larger influenza epidemics in subsequent years.
Publisher: Elsevier BV
Date: 02-2019
Publisher: American Chemical Society (ACS)
Date: 13-07-2020
DOI: 10.1021/ACS.ANALCHEM.0C02048
Abstract: Heparan sulfate and heparin are highly acidic polysaccharides with a linear sequence, consisting of alternating glucosamine and hexuronic acid building blocks. The identity of hexuronic acid units shows a variability along their sequence, as d-glucuronic acid and its
Publisher: Oxford University Press (OUP)
Date: 12-10-2011
Publisher: Wiley
Date: 30-03-2018
Publisher: Wiley
Date: 31-01-2019
DOI: 10.1111/MMI.14197
Publisher: American Chemical Society (ACS)
Date: 06-04-2023
Publisher: Cold Spring Harbor Laboratory
Date: 11-05-2018
DOI: 10.1101/312157
Abstract: Biosynthesis of the nucleotide sugar precursor dTDP-L-rhamnose is critical for the viability and virulence of many human pathogenic bacteria, including Streptococcus pyogenes (Group A Streptococcus GAS) and Streptococcus mutans . Those pathogens require dTDP-L-rhamnose for the production of structurally similar rhamnose polysaccharides in their cell wall. Via heterologous expression in S. mutans , we confirm that GAS RmlB and RmlC are critical for dTDP-L-rhamnose biosynthesis through their action as dTDP-glucose-4,6-dehydratase and dTDP-4-keto-6-deoxyglucose-3,5-epimerase enzymes, respectively. Complementation with GAS RmlB and RmlC containing specific point mutations corroborated the conservation of previous identified catalytic residues in these enzymes. Bio-layer interferometry was used to identify and confirm inhibitory lead compounds that bind to GAS dTDP-rhamnose biosynthesis enzymes RmlB, RmlC and GacA. One of the identified compounds, Ri03, inhibited growth of GAS as well as several other rhamnose-dependent streptococcal pathogens with an MIC 50 of 120-410 μM. We therefore conclude that inhibition of dTDP-L-rhamnose biosynthesis such as Ri03 affect streptococcal viability and can serve as a lead compound for the development of a new class of antibiotics that targets dTDP-rhamnose biosynthesis in pathogenic bacteria.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2022
DOI: 10.1038/S41589-021-00924-1
Abstract: Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (K
Publisher: American Chemical Society (ACS)
Date: 07-08-2019
Publisher: Wiley
Date: 10-2015
DOI: 10.1111/MMI.13169
No related grants have been discovered for Geert-Jan Boons.