ArticleChemical science2019
Syntheses of defined sulfated oligohyaluronans reveal structural effects, diversity and thermodynamics of GAG-protein binding.
Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- Total Synthesis of Conjugation-Ready Sulfated Red Algae Carrageenan Oligosaccharides for Sensing Applications.Journal of the American Chemical Society · 2026Article
- Synthesis of Sulfated Glycomimetics with Micromolar Affinity for Midkine.The Journal of organic chemistry · 2026Article
- Glycosaminoglycans as Polyelectrolytes: Charge, Interactions, and Applications.Chembiochem : a European journal of chemical biology · 2025Review
- Computational toolbox for the analysis of protein-glycan interactions.Beilstein journal of organic chemistry · 2024Review
- Sulfation of Heparan and Chondroitin Sulfate Ligands Enables Cell-Specific Homing of Nanoprobes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Respiratory viruses interacting with cells: the importance of electrostatics.Frontiers in microbiology · 2023Review
- The CXCL12/CXCR4/ACKR3 Response Axis in Chronic Neurodegenerative Disorders of the Central Nervous System: Therapeutic Target and Biomarker.Cellular and molecular neurobiology · 2022Review
- Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.Scientific reports · 2022Article
- Thermodynamic Affinity and Nature of Forces Defining Glycosaminoglycan-Protein Systems Using Fluorescence Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration.Frontiers in cell and developmental biology · 2021Review
- Sulfation modulates the targeting properties of hyaluronic acid to P-selectin and CD44.ACS biomaterials science & engineering · 2020Article
- IR action spectroscopy of glycosaminoglycan oligosaccharides.Analytical and bioanalytical chemistry · 2020Article
- Dual Action of Sulfated Hyaluronan on Angiogenic Processes in Relation to Vascular Endothelial Growth Factor-A.Scientific reports · 2019Article
- Unraveling Heparan Sulfate Proteoglycan Binding Motif for Cancer Cell Selectivity.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Binding of sulfated glycosaminoglycans (GAG) to a wide spectrum of extracellular regulatory proteins is crucial for physiological processes such as cell growth, migration, tissue homeostasis and repair. Thus, GAG derivatives exhibit great relevance in the development of innovative biomaterials for tissue regeneration therapies. We present a synthetic strategy for the preparation of libraries of defined sulfated oligohyaluronans as model GAG systematically varied in length, sulfation pattern and anomeric substitution in order to elucidate the effects of these parameters on GAG recognition by regulatory proteins. Through an experimental and computational approach using fluorescence polarization, ITC, docking and molecular dynamics simulations we investigate the binding of these functionalized GAG derivatives to ten representative regulatory proteins including IL-8, IL-10, BMP-2, sclerostin, TIMP-3, CXCL-12, TGF-β, FGF-1, FGF-2, and AT-III, and we establish structure-activity relationships for GAG recognition. Binding is mainly driven by enthalpy with only minor entropic contributions. In several cases binding is determined by GAG length, and in all cases by the position and number of sulfates. Affinities strongly depend on the anomeric modification of the GAG. Highest binding affinities are effected by anomeric functionalization with large fluorophores and by GAG dimerization. Our experimental and theoretical results suggest that the diversity of GAG binding sites and modes is responsible for the observed high affinities and other binding features. The presented new insights into GAG-protein recognition will be of relevance to guide the design of GAG derivatives with customized functions for the engineering of new biomaterials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.