bims-supasi Biomed News
on Sulfation pathways and signalling
Issue of 2026–09–20
six papers selected by
Jonathan Wolf Mueller, University of Birmingham



  1. Int J Biol Macromol. 2026 Sep 15. pii: S0141-8130(26)04470-3. [Epub ahead of print]382(Pt 2): 154522
      Chronic and infected wounds expose a structural deficit in regenerative biomaterials: the native glycosaminoglycan (GAG) machinery that organizes growth-factor gradients, restrains proteolysis, and sets immune tone is absent, degraded, or pathologically remodeled. GAG-mimetic polysaccharides sulfated marine, microbial, and engineered carbohydrates that reproduce the charge chemistry of heparin, heparan sulfate, and chondroitin sulfate without their supply and safety liabilities offer a route to rebuild that machinery on demand. This review explores the carbohydrate-polymer logic linking primary structure to repair outcome. Sulfation degree and, more consequentially, sulfation position and charge patterning govern the affinity and selectivity with which these polymers capture FGF-2, VEGF, TGF-beta, PDGF, and BMPs, and the extent to which they competitively sequester chemokines, complement components and matrix proteins. The same anionic, hydrated interfaces that concentrate morphogens also resist bacterial adhesion, perturb biofilm assembly, and serve as depots for antimicrobial peptides, thereby coupling pro-regenerative and anti-infective functions within a single backbone. We evaluate heparin, heparan sulfate, hyaluronan, chondroitin and dermatan sulfate, fucoidan, carrageenan, ulvan, and sulfated cellulose, chitosan, and alginate, alongside defined synthetic glycopolymers, and trace how molecular weight, chain flexibility, and hydrogel presentation modulate angiogenesis, fibroblast and keratinocyte behavior, and macrophage polarization. Persistent translational barriers uncontrolled anticoagulation, oversulfated-contaminant toxicity, immunogenicity, batch heterogeneity, and degradation mismatch are examined critically. We emphasize that position-resolved sulfation control, not maximal charge, is the decisive design variable for the next generation of infection-resistant regenerative matrices. Binding is treated here as a property of the pair rather than of the polysaccharide alone: clustered basic residues, reversible monomer-dimer equilibria and higher-order oligomerisation on the morphogen side determine how growth factors and chemokines are sequestered, how haptotactic gradients form, and how neutrophils are recruited, and these traits constrain which mimetic structures can work. Chemokine sequestration is defined mechanistically rather than invoked, and the practical constraints specific to marine-derived complex polysaccharides-structural heterogeneity, process-written sulfation, contaminant carry-over and the absence of mammalian catabolic machinery are set out alongside the characterisation each one demands.
    Keywords:  Antibiofilm interfaces; Charge patterning; Glycosaminoglycan mimetics; Growth-factor binding; Heparan sulfate; Immunomodulation; Sulfated polysaccharides; Wound repair
    DOI:  https://doi.org/10.1016/j.ijbiomac.2026.154522
  2. Angew Chem Int Ed Engl. 2026 Sep 15. e2218878
      N- and O-glycosylations are essential post-translational modifications involved in numerous physiological and pathological processes. Sulfated N- and O-glycans, commonly found on biologically important glycoproteins, serve as critical mediators of molecular recognition. However, their precise structure-function relationships remain poorly understood, primarily due to the limited accessibility of structurally well-defined glycans bearing branch-specific sulfation patterns. Herein, we report a versatile chemoenzymatic strategy that integrates chemical synthesis of editable glycan scaffolds with enzyme-driven diversification, enabling the efficient construction of a diverse library of branch-specifically sulfated N- and O-glycans, along with their nonsulfated counterparts. Central to the strategy is the streamlined chemical synthesis of editable N- and O-glycan precursors bearing two orthogonally protected glucosamine termini, allowing branch-selective sulfation through flexible protecting-group manipulation. Subsequent modular enzymatic extension readily generates a panel of sulfated glycans with sialylation and fucosylation patterns. These diverse structures enable comprehensive profiling of their interactions with immune-associated lectins and viral proteins using microarray technology, uncovering unique binding specificities modulated by branch-specific sulfation patterns and core glycan architectures. This work establishes a powerful synthetic approach to previously inaccessible complex sulfated N- and O-glycans, providing critical tools to advance glycobiology and biomedical applications.
    Keywords:  biomolecular recognition; carbohydrates; chemoenzymatic synthesis; glycosylation; sulfated glycans
    DOI:  https://doi.org/10.1002/anie.2218878
  3. Methods Mol Biol. 2026 ;3060 643-660
      Understanding the cryobiological responses of endothelial cells is important to ensure the successful cryopreservation of vascularized tissues and organs. The endothelium, a monolayer of endothelial cells comprising the inner lining of blood vessels and other tissues such as the cornea, is sensitive to cryoinjury. In this chapter, we update our published cryopreservation protocol, which we have since validated for several more cell types. Our optimized protocol involves culturing cells on Rinzl plastic coverslips, using a combination of a permeating cryoprotectant (5% dimethyl sulfoxide) and a non-permeating cryoprotectant (6% hydroxyethyl starch), addition of 2% chondroitin sulfate, controlled-rate slow cooling, storage in liquid nitrogen, and removal of cryoprotectants immediately after thaw. Our post-thaw assessments include membrane integrity and a functional assay immediately after thaw and after extended incubation in culture conditions.
    Keywords:  AlamarBlue reduction; Chondroitin sulfate; Cryopreservation; Delayed-onset cryoinjury; Dimethyl sulfoxide; Fluorescent microscopy; Graded freezing; Hydroxyethyl starch; Membrane integrity; Rinzl plastic
    DOI:  https://doi.org/10.1007/978-1-0716-5416-3_28
  4. J Food Sci. 2026 Sep;91(9): e71441
      Polysaccharides derived from natural sources exhibit significant antidiabetic activity, yet the application of some polysaccharides is limited by their poor solubility, low stability, and limited bioavailability. Sulfation has emerged as an effective strategy to enhance these properties by introducing sulfate groups onto polysaccharide structures. Numerous studies have described and assessed the biological properties of sulfated polysaccharides and their associations, highlighting their significant potential for antidiabetic activity. This review systematically summarizes the methods of sulfation modification and evaluates their advantages and disadvantages. The influence of sulfation on crucial physicochemical characteristics such as solubility, thermal stability, and viscosity is analyzed, along with changes in monosaccharide compositi, molecular weight, glycosidic linkages, and chain conformation. Sulfated polysaccharides demonstrate significantly improved antidiabetic effects through various mechanisms, including inhibition of digestive enzymes, modulation of gut microbiota leading to regulation of short-chain fatty acids and glucagon-like peptide-1, activation of insulin signaling and AMP-activated protein kinase (AMPK) pathways, suppression of inflammatory responses, and systemic metabolic alterations involving branched-chain amino acids, bile acids, and lipid profiles. Overall, sulfation modification technology holds great potential for enhancing the antidiabetic properties of polysaccharides.
    Keywords:  antidiabetic activity; mechanism; polysaccharide; structural characteristics; sulfation modification
    DOI:  https://doi.org/10.1111/1750-3841.71441
  5. Bioact Mater. 2027 Feb;68 148-161
      Osteoarthritis (OA) is characterized by progressive glycosaminoglycan (GAG) depletion caused by insufficient matrix replenishment and excessive proteoglycan catabolism. Here, we developed a spatially coordinated strategy that integrates GAG deposition in the cartilage extracellular matrix (ECM) with intracellular regulation of GAG enrichment and degradation in chondrocytes. To achieve this strategy, we engineered a hierarchical "Nanorocket" comprising a chondroitin sulfate (CS)-cationic peptide Booster and an HDMBr/siADAMTS5 Satellite. The Nanorocket facilitated cartilage penetration and prolonged the intra-articular retention of both components. The Booster supported CS deposition within the cartilage extracellular matrix, whereas the internalized Satellite increased CHPF/CHSY2 expression and silenced ADAMTS5, thereby promoting GAG enrichment while limiting proteoglycan degradation. This coordinated regulation preserved GAG content, reduced matrix porosity, and maintained the mechanical properties of human cartilage explants. In a surgical OA mouse model, periodic treatment preserved cartilage thickness and matrix integrity, mitigated subchondral bone alterations, and improved gait performance. These findings establish the proof-of-concept feasibility of spatially coordinating GAG deposition and metabolism to preserve cartilage homeostasis during early OA progression.
    Keywords:  ECM metabolic homeostasis; Glycosaminoglycan; Osteoarthritis intervention; RNA delivery
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.08.047
  6. Life Sci. 2026 Sep 16. pii: S0024-3205(26)00497-2. [Epub ahead of print] 124688
       AIMS: Increasing evidence on the gut-kidney axis has highlighted the critical role of the gut microbiota in maintaining renal function. This study investigated the protective effects of a probiotic mixture (PM) in a cisplatin-induced kidney injury model and explored its potential mechanisms through modulation of uremic toxins and gut microbiota composition.
    MATERIALS AND METHODS: Probiotic strains were initially evaluated for their ability to remove indole, a microbial precursor of the uremic toxin indoxyl sulfate (IS). The renoprotective effects of individual strains and a composite probiotic formulation were then compared in a cisplatin-induced animal model. Changes in gut microbiota composition following administration of the composite formulation were analyzed, and correlation analyses were performed between microbial profiles and biomarkers of renal injury.
    KEY FINDINGS: The selected probiotic strains exhibited significantly greater indole removal capacity in vitro with day-3 reductions of 49.3-87.7%. In vivo, administration of the composite probiotic formulation attenuated cisplatin-induced body weight loss, hepatic injury, and renal dysfunction. These protective effects were accompanied by alterations in gut microbiota composition and reduced circulating uremic toxins. Cisplatin increased serum IS and p-cresyl sulfate (pCS) concentrations by approximately 5- and 13-fold, respectively, whereas probiotic treatment significantly attenuated both increases. Correlation analysis revealed associations between specific microbial taxa and renal injury biomarkers.
    SIGNIFICANCE: These findings suggest that probiotic supplementation may exert renoprotective effects by reducing gut-derived uremic toxins and modulating the gut microbiota. Targeting the gut-kidney axis through probiotic intervention may represent an adjunctive strategy for preventing cisplatin-induced nephrotoxicity.
    Keywords:  Cisplatin-induced nephrotoxicity; Gut microbiota; Gut–kidney axis; Probiotics; Uremic toxins
    DOI:  https://doi.org/10.1016/j.lfs.2026.124688