bims-supasi 2026-10-11 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–10–11
eleven papers selected by
Jonathan Wolf Mueller, University of Birmingham

Orally administered chondroitin sulfate oligosaccharides attenuate hypertension via multiple protective pathways, including Hmox1-mediated antioxidant responses.
Heparan Sulfate Oligosaccharides Modulate SARS-CoV-2 Spike-Host Recognition.
Chondroitin Sulfate as a Bioactive Carbohydrate: Design of Nanoplatforms for Drug Delivery, Tissue Engineering, and Disease Therapy.
Chondroitin sulfate in inflammatory joint diseases: How structural variability shapes its therapeutic effects.
Characterization of glycosaminoglycan modifications and a related galactosyltransferase B4GALT7 in Bombyx mori.
Salmon bone-derived chondroitin sulfate nanogels for controlled delivery of curcumin: release behavior, structural characteristics and anti-inflammatory efficacy.
The role of glycocalyx-protein corona interactions in the cell type-specific uptake of mRNA nanocarriers.
Post-translational control of synaptic adhesion molecules: molecular mechanisms and disease implications.
Analysis of sulfated sialic acids by liquid chromatography coupled with high-resolution mass spectrometry and fluorescence detection.
Structural and functional analysis of KfiA, a UDP-GlcNAc transferase involved in Escherichia coli K5 heparosan biosynthesis.
Sensitive Fluorescent Detection of Heparin and Protamine Using a Propidium Iodide-Based Sensing System.

Glycobiology. 2026 Oct 03. pii: cwag087. [Epub ahead of print]

Orally administered chondroitin sulfate oligosaccharides attenuate hypertension via multiple protective pathways, including Hmox1-mediated antioxidant responses.

Hiroko Mizuta, Kosuke Nakamura, Misako Yamaguchi, Masanori Yamaguchi, Nobuyuki Miyamoto.

  Chondroitin sulfate (CS) is a sulfated glycosaminoglycan with various physiological functions. We previously prepared a mixture of chondroitin sulfate oligosaccharides (CSOS) derived from skate cartilage and evaluated its absorption in humans using urinary CS excretion as an indicator. The results suggested that CSOS is absorbed more efficiently than intact high-molecular-weight CS (HMwCS). However, the plasma pharmacokinetics and biological effects of CSOS after administration remained unclear. The present study aimed to clarify these aspects. Pharmacokinetic analysis based on plasma exogenous CS concentrations revealed that CSOS was absorbed, whereas no absorption of HMwCS was observed. Consistent with this finding, a Caco-2 cell assay using CS with different molecular weights showed that lower-molecular-weight CS had greater permeability. To investigate the biological potential of absorbed CSOS, we evaluated its antihypertensive activity in spontaneously hypertensive rats (SHR/Kpo) and explored the underlying mechanisms using microarray analysis. CSOS administration for 12 weeks significantly attenuated hypertension in SHR/Kpo rats. Microarray analysis revealed altered gene expression in analyzed tissues. Among them, we focused on the upregulation of heme oxygenase-1 (Hmox1) in arterial vessels and blood, which has been implicated in oxidative stress-related blood pressure regulation. To evaluate the effect of CSOS on HMOX1 expression, its constituent CS oligomers were examined in EAhy.926 endothelial cells. CS disaccharide (CS2-mer) induced HMOX1 expression, consistent with transcription factor activation. Comparison of CS2-mer analogs indicated that the C6-sulfated disaccharide induced HMOX1 expression without cytotoxicity. These findings suggest that CSOS attenuates hypertension partly through vascular HMOX1 induction, possibly involving the C6-sulfated disaccharide.

Keywords:  chondroitin sulfate oligosaccharides; heme oxygenase-1; hypertension; intestinal absorption; nuclear factor erythroid 2–related factor 2

DOI:  https://doi.org/10.1093/glycob/cwag087
Chembiochem. 2026 Oct 14. 27(19): e70567

Heparan Sulfate Oligosaccharides Modulate SARS-CoV-2 Spike-Host Recognition.

Binjie Li, Tianji Zhang, Mingjia Yu.

  Heparan sulfate (HS) is a key host-factor mediator of SARS-CoV-2 attachment and an attractive target for antiviral intervention, yet the synthesis of structurally defined HS oligosaccharides remains challenging. Here, we show that a defined HS hexasaccharide, heparin-dp6, efficiently inhibits RBD-ACE2 binding and exhibits superior antiviral activity compared with longer HS mimetics. Electronic-structure analyses suggest that the strong recognition capacity of HS arises from sulfate and carboxylate groups, which create highly negative electrostatic surfaces and serve as dominant hydrogen-bond acceptors, governing charge distribution and electronic properties along the glycan backbone to modulate binding specificity and affinity. Stepwise virtual screening of a comprehensive HS database further identified several high-affinity oligosaccharides, with top candidates displaying favorable RBD-binding properties. These findings indicate that HS activity is determined not only by chain length and sulfation pattern, but also by the spatial arrangement of charged functional groups, providing mechanistic insight into HS-RBD recognition and guiding the rational design of HS-based decoy inhibitors against SARS-CoV-2 entry.

Keywords:  RBD; SARS‐CoV‐2; heparan sulfate; protein‐binding; virtual screening

DOI:  https://doi.org/10.1002/cbic.70567
ACS Appl Bio Mater. 2026 Oct 03.

Chondroitin Sulfate as a Bioactive Carbohydrate: Design of Nanoplatforms for Drug Delivery, Tissue Engineering, and Disease Therapy.

Anam Shabbir, Mazeyar Parvinzadeh Gashti.

  Chondroitin sulfate (CS), a sulfated glycosaminoglycan, has attracted considerable attention in nanomedicine owing to its excellent biocompatibility, biodegradability, and intrinsic bioactivity. Recent advances in CS-based nanoplatforms, including nanogels, nanoparticles, hydrogels, and other drug delivery systems, have enabled targeted drug delivery, tissue engineering, and regenerative medicine applications. These multifunctional systems facilitate controlled drug release, enhance cellular uptake, and regulate key biological processes such as inflammation, oxidative stress, and extracellular matrix remodeling. Beyond their roles in material design, CS-based nanoplatforms have demonstrated promising preclinical potential in cancer therapy, osteoarthritis, periodontitis, cartilage regeneration, wound healing, ophthalmic disorders, liver fibrosis, and neurodegenerative diseases. This review first discusses the design principles and functional characteristics of CS-based material platforms followed by their therapeutic applications in tissue engineering and disease treatment. Finally, the current challenges, translational perspectives, and future opportunities for the clinical development of CS-based nanoplatforms are highlighted.

Keywords:  anti-inflammatory therapy; cartilage regeneration; chondroitin sulfate; drug delivery; nanoplatforms; periodontitis; tissue engineering

DOI:  https://doi.org/10.1021/acsabm.6c00711
Int J Biol Macromol. 2026 Oct 09. pii: S0141-8130(26)04750-1. [Epub ahead of print] 154800

Chondroitin sulfate in inflammatory joint diseases: How structural variability shapes its therapeutic effects.

Kátia Alves Ribeiro, Vitor Alfredo de Santana Silva, Mariana Alves Soares, Angela Magalhães Vieira, Marton Kaique de Andrade Cavalcante, Valéria Rêgo Alves Pereira, Maria Tereza Dos Santos Correia, Ana Luísa Palhares de Miranda, Maria das Graças Carneiro-da-Cunha, Paulo Antônio de Souza Mourão, Mariana Sá Pereira, Paulo Antônio Galindo Soares.

  Inflammatory joint diseases, including rheumatoid arthritis and osteoarthritis (OA), are characterized by pain, inflammation, and progressive cartilage degeneration. Chondroitin sulfate (CS) is widely used as a symptomatic treatment, but the influence of structural variability on its biological activity remains unclear. We compared two pharmaceutical CS preparations with distinct structural features: CS-A, predominantly 4-sulfated, and CS-C, predominantly 6-sulfated. Disaccharide composition was determined by chondroitinase AC digestion followed by SAX-HPLC and compared with previously reported HSQC NMR data. Biological effects were evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats and monosodium iodoacetate (MIA)-induced OA in mice. Hypernociception, edema, locomotor behavior, inflammatory mediators, myeloperoxidase (MPO) activity, leukocyte migration, and histopathological alterations were assessed. Both preparations attenuated inflammatory and joint alterations without signs of systemic toxicity. In the CFA model, CS-A and CS-C increased the hypernociceptive threshold by 52.71% and 53.28% and reduced MPO activity by 84.7% and 70.2%, respectively. In the MIA model, they increased the hypernociceptive threshold by 69.7% and 37.3% and reduced synovial inflammatory infiltration by 98% and 70%, respectively. Both preparations reduced IL-6, TNF-α, and PGE₂, whereas CS-A markedly increased IL-10. Histological analyses showed reduced inflammatory damage, increased tibial chondrocyte area, and lower OARSI scores. Overall, both CS preparations exhibited anti-inflammatory, antihypernociceptive, and chondroprotective effects, with response magnitude varying across outcomes. These findings suggest that structural characteristics, including sulfation pattern and molecular weight, may contribute to differences in CS biological activity.

Keywords:  Chondroitin sulfate; Hypernociception; Inflammation; Sulfation pattern; Therapeutic activity

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.154800
Int J Biol Macromol. 2026 Oct 03. pii: S0141-8130(26)04681-7. [Epub ahead of print] 154731

Characterization of glycosaminoglycan modifications and a related galactosyltransferase B4GALT7 in Bombyx mori.

Feifei Zhu, Wen Tao, Tingting Xue, Qi Tang, Qian Yu, Lindan Sun, Guohui Li, Shangshang Ma, Xiaoyong Liu, Keping Chen.

  Glycosaminoglycan (GAG) modifications mediate multiple biological processes, yet the GAG modification landscape remains poorly characterized, especially in invertebrates. The silkworm Bombyx mori is an important economic insect, a lepidopteran model species, and a promising bioreactor for recombinant protein production. Herein, we profiled the GAG modifications in Bombyx mori and identified 21 chondroitin sulfate (CS)-modified proteoglycans. Bioinformatic analyses indicate that several of these proteoglycans participate in cytoskeletal organization, cell adhesion, and immune response, whereas the majority still lack sufficient functional annotation or reference information from homologs. We further characterized silkworm B4GALT7, a core enzyme participating in the biosynthesis of the tetrasaccharide linkage of GAG, and demonstrated that B4GALT7 could positively regulate global GAG modification levels in silkworm cells. Silkworm B4GALT7 localizes to the Golgi apparatus and displays broad substrate tolerance toward several sugar donors and diverse acceptors including xylose, pNP-sugars and phenolic compounds, exhibiting enzymatic features distinct from its human and Drosophila homologs. Its optimal catalytic conditions were defined as 25 °C, pH 7.0, and 1 mM Ca2+. This study establishes the first CS-proteoglycan profiles in B. mori, and characterized a GAG biosynthetic enzyme, B4GALT7, providing a fundamental basis for further exploration of the structures and functions of GAG modification in this model insect.

Keywords:  Galactosyltransferase; Glycosaminoglycan; Silkworm

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.154731
RSC Adv. 2026 Oct 05.

Salmon bone-derived chondroitin sulfate nanogels for controlled delivery of curcumin: release behavior, structural characteristics and anti-inflammatory efficacy.

Quang Van Ngo, Nguyen Chi Nguyen, Hong Thi Pham, Cuong Duc Ho, Thu Thi Minh Quach, Thuy Thi Thu Thanh.

Marine-derived polysaccharides have emerged as sustainable biomaterials for advanced drug delivery; however, the relationship between their molecular organization and drug release behavior remains insufficiently understood. In this study, chondroitin sulfate (CS) extracted from salmon bone was utilized to fabricate Ca2+-crosslinked nanogels for the controlled delivery of curcumin (Cur). The optimized nanogels exhibited a hydrodynamic diameter of 217.3 ± 15.6 nm, a polydispersity index of 0.25 ± 0.02, and a negative zeta potential of -26.9 ± 0.14 mV, indicating good colloidal stability. Comprehensive structural characterization via FT-IR and XRD indicated that the nanogel framework is stabilized by Ca2+-mediated ionic crosslinking and multi-point hydrogen bonding. Notably, XRD analysis revealed that while encapsulated curcumin primarily adopts an amorphous molecular dispersion, the emergence of a specific reflection at 2θ ≈ 14° suggests that a minor fraction adopts a locally ordered state stabilized within the nanogel microenvironment. The nanogels demonstrated a sustained biphasic release profile governed by anomalous (non-Fickian) diffusion (n = 0.711). Furthermore, in LPS-stimulated RAW 264.7 macrophages, the CS-Cur nanogels showed significantly enhanced anti-inflammatory efficacy and high biocompatibility compared to free curcumin. These findings highlight salmon bone-derived CS as a sustainable, high-performance matrix for hydrophobic drug delivery, providing new insights into the role of cargo-induced structural organization in regulating therapeutic release and biological performance.

DOI: https://doi.org/10.1039/d6ra06378k
J Control Release. 2026 Oct 06. pii: S0168-3659(26)00844-8. [Epub ahead of print] 115440

The role of glycocalyx-protein corona interactions in the cell type-specific uptake of mRNA nanocarriers.

Ward Jacobs, Klarinda de Zwaan, Luco Rutten, Thierry van Wessel, Thomas J Boltje, Laia Querol Cano, Christian Büll, Nico Sommerdijk, Lorenzo Albertazzi, Roland Brock.

  Non-viral nanocarriers for oligonucleotide delivery have enormous therapeutic potential, but the factors determining cell type-specific uptake remain incompletely understood. One major cell surface component that delivery vectors encounter is the glycocalyx. While membrane glycans are established interactors for many viruses, their impact on non-viral particles has remained underexplored. Here, we show that the role of membrane glycosaminoglycans (GAGs) in mRNA delivery differs across nanocarrier categories and cell types. We employed novel glycosylation inhibitors as well as enzymatic strategies to modulate the glycocalyx, and measured their effects on mRNA delivery efficiency. Metabolic labelling enabled colocalization analysis of glycans with mRNA. Whereas lipoplexes and lipid nanoparticles (LNPs) require an intact glycocalyx for uptake by HeLa cervical cancer cells, a cationic peptide-based formulation does not. Heparan sulfate (HS) is the most important GAG for LNP uptake. Further experiments demonstrate that this interaction is mediated through HS-binding proteins of the protein corona, such as ApoE and vitronectin. HS-dependence varied across cell types: whereas HeLa and HCT116 tumor cells strongly depend on HS for LNP uptake, primary dendritic cells, normal human dermal fibroblasts, and MCF-7 breast cancer cells did not. HepG2 cells showed mild HS-dependence. Across all cell types, HS-dependence directly correlated with LNP uptake and expression, providing new mechanistic insight into why mRNA nanoparticles display cell-selective uptake.

Keywords:  Drug delivery; Glycocalyx; Lipid nanoparticles; Nanomedicine; Protein corona; mRNA

DOI:  https://doi.org/10.1016/j.jconrel.2026.115440
BMB Rep. 2026 Oct 07. pii: 6913. [Epub ahead of print]

Post-translational control of synaptic adhesion molecules: molecular mechanisms and disease implications.

Seo-Young Yun, Ji-Hye Song, Kyung Ah Han.

Synaptic cell adhesion molecules (SAMs) are crucial for organizing synapse formation, maturation, and plasticity. No longer considered static structural links between pre- and postsynaptic membranes, SAMs are now understood to be dynamic signaling platforms whose functions are precisely controlled by various post-translational modifications (PTMs). For instance, conventional N- and O-linked glycosylation regulates protein folding and surface trafficking, whereas proteoglycan modification by heparan sulfate (HS) contributes to extracellular recognition and trans-synaptic interactions. Meanwhile, phosphorylation and dephosphorylation influence scaffold recruitment, synapse type specificity, and activity-dependent signaling. Additionally, proteolytic processing and ubiquitination manage the turnover, endocytosis, and signaling duration of adhesion complexes, allowing for rapid changes in synaptic connectivity. This review synthesizes recent progress on how these PTMs regulate SAMs and neurotrophin receptors across different scales, from individual synapses to entire neural circuits. We also discuss how PTM dysregulation contributes to neurodevelopmental and neuropsychiatric disorders and highlight the possibility that interactions among distinct PTMs may form a combinatorial regulatory code that further diversifies synaptic adhesion signaling, although this concept requires further investigation.
BBA Adv. 2026 ;10 100203

Analysis of sulfated sialic acids by liquid chromatography coupled with high-resolution mass spectrometry and fluorescence detection.

Sota Yamashita, Takayuki Omoto, Nao Yamakawa, Naoko Komura, Hiromune Ando, Di Wu, Ken Kitajima, Masaya Hane, Chihiro Sato.

  Sialic acid is localized at the outermost glycan, and involved in regulatory roles as one of the most important glycotopes in various biological phenomena. Recently, we established a highly sensitive and selective method for the fine differentiation of 1,2-diamine-4,5-methylenedioxybenzene (DMB)-labeled sialic acids, including N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), deaminoneuraminic acid (Kdn), and their O-acetyl derivatives. This approach enables unambiguous identification of these three sialic acids based on characteristic C-5 diagnostic fragment ions obtained by high-resolution accurate-mass spectrometry and fluorescence detection. In the present study, we extended this analytical platform to sulfated sialic acids (SiaSs) to evaluate its applicability to sialic acids bearing an additional negatively charged sulfate group. We first assessed the liquid chromatographic separation of DMB-labeled SiaSs using authentic standards. Using a CAPCELL PAK ADME column, we successfully separated six authentic SiaS standards and three previously unreported SiaS species in sea urchins. We identified multiple O-sulfated substitutions on Neu5Ac and Neu5Gc species, which were further confirmed by characteristic collision-induced dissociation (CID) fragmentation. In addition, electron-activated dissociation (EAD) was employed to evaluate the fragmentation behavior of SiaS species. EAD analyses efficiently generated characteristic diagnostic ions that enable reliable discrimination of the sulfation site, allowing clear differentiation between 8-O- and 9-O-sulfated isomers. Liquid chromatography-based fragment analysis led to the identification of a novel O-sulfated and O-acetylated sialic acid, Neu5Gc8SOAc1, which had never been reported before. These findings underscore the complementary nature of fluorescence detection and high-resolution mass spectrometry techniques for the identification and quantification of DMB-labeled sialic acids.

Keywords:  Collision-induced dissociation; Electron-activated dissociation; Fluorescence detection; High-resolution mass spectrometry; Sialic acid; Sulfated sialic acid

DOI:  https://doi.org/10.1016/j.bbadva.2026.100203
Carbohydr Res. 2026 Oct 07. pii: S0008-6215(26)00312-5. [Epub ahead of print]570 110123

Structural and functional analysis of KfiA, a UDP-GlcNAc transferase involved in Escherichia coli K5 heparosan biosynthesis.

Kento Maeda, Aya Sakamoto, Kyoka Matsuura, Kota Toyoda, Hiroka Hori, Momo Onishi, Yuuichi Baba, Yoshirou Kawaguchi, Yohei Ishibashi, Nozomu Okino, Etsuko Nishimoto, Nobuo Sugiura, Takamasa Teramoto, Yoshimitsu Kakuta.

  Heparosan is a linear glycosaminoglycan-related polysaccharide produced as the capsular polysaccharide of Escherichia coli K5. Its biosynthesis requires alternating transfer of N-acetylglucosamine and glucuronic acid by the glycosyltransferases KfiA and KfiC, respectively, but the structural basis of KfiA function has remained unclear. Here, we determined crystal structures of a C-terminally truncated KfiA in the apo state and in complex with UDP and a metal ion tentatively assigned as Mn2+, and combined structural analysis with functional characterization. KfiA adopts a conserved GT-A fold with a well-defined nucleotide- and metal-binding center. Structural and biochemical analyses further distinguish the core donor-associated catalytic region from peripheral structural elements that contribute to efficient glycosyl transfer. Comparison with related glycosyltransferases reveals a conserved structural framework for UDP-GlcNAc utilization. These results provide a structural basis for understanding KfiA function and heparosan chain extension in the two-enzyme KfiA-KfiC system.

Keywords:  Escherichia coli K5; Glycan chain extension; Glycosaminoglycan biosynthesis; Glycosyltransferase; Heparosan biosynthesis

DOI:  https://doi.org/10.1016/j.carres.2026.110123
Luminescence. 2026 Oct;41(10): e70641

Sensitive Fluorescent Detection of Heparin and Protamine Using a Propidium Iodide-Based Sensing System.

Ying Feng, Gongli Wei, Ce Wang, Changyao Liu, Li Zhao.

  Heparin and protamine are important biological macromolecules that play vital roles in the physiological processes and clinical medicine. The utilization of commercially available fluorescent probes for the quantitative detection of heparin and protamine circumvents the necessity for laborious organic synthesis, thereby facilitating a cost-effective, fast-response, and highly sensitive fluorescent detection. In this work, propidium iodide (PI) was selected as a fluorescent probe for the sensing of heparin and protamine. The results demonstrated that PI underwent aggregation on the heparin surface, driven by electrostatic interactions, resulting in fluorescence quenching. The fluorescence intensity exhibited a linear relationship with heparin concentration in the range of 0-6.67 μg/mL, with a detection limit of 0.12 μg/mL. Utilizing the electrostatic complex system of PI and heparin as a probe, the quantitative detection of protamine-the antidote to heparin-can be achieved, based on the high affinity between heparin and protamine. The PI-based detection of heparin and protamine has been demonstrated to be applicable not only in HEPES buffer but also in solutions containing 1% fetal bovine serum. This finding indicates its potential for use in complex media.

Keywords:  fluorescence detection; heparin; propidium iodide; protamine

DOI:  https://doi.org/10.1002/bio.70641