Binding of oligosaccharides of hyaluronic acid to proteoglycans.
Ontology highlight
ABSTRACT:
SUBMITTER: Hardingham TE
PROVIDER: S-EPMC1165913 | biostudies-other | 1973 Dec
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Highly efficient syntheses of hyaluronic acid oligosaccharides have been accomplished through the pre-activation based iterative one-pot strategy. A series of oligosaccharides ranging from di- to hexasaccharides were rapidly assembled using only near stoichiometric amounts of the building blocks without aglycon adjustment or purifications of intermediate oligosaccharides. Deprotection and oxidation protocols were developed for protective group removal and oxidation-state adjustment. The availability of such structurally well defined synthetic hyaluronic acid oligosaccharides will greatly facilitate the establishment of detailed structure-function relationships.
| S-EPMC1820888 | biostudies-literature
Project description:Hyaluronic acid-derived oligomers of five to fifteen repeat dissaccharides effectively bind to bovine nasal-cartilage proteoglycan and inhibit the interaction between proteoglycans and high-molecular-weight hyaluronic acid. If, however, the hyaluronic acid oligosaccharides are modified by reaction with diazomethane to form the carboxyl methyl esters of the glucuronic acid residues, their inhibitory activity is abolished. The binding capacity can be fully restored by saponification. The amide derivative, which is formed by condensation of the oligosaccharide carboxyl groups with glycine methyl ester, is also ineffective in blocking the proteoglycan-hyaluronic acid interaction. In this case, binding activity is not restored when the amidated oligomers are subjected to saponification to yield the free carboxylate groups on the glycine residues. Thus the displacement of the carboxylate groups on the polysaccharide chain by the interposition of a glycine residue blocks the interaction between the proteoglycans and the hyaluronic acid oligomers. When the oligosaccharide methyl ester is reduced with NaBH4, the resultant glucose-containing oligomers exhibit decreased binding to proteoglycans. Thus it appears that the hyaluronic acid carboxylate anion in a specific spatial orientation is required for hyaluronic acid-proteoglycan interaction.
| S-EPMC1183718 | biostudies-other
Project description:Hyaluronic acid (hyaluronan, HA) is a critical component of the extracellular matrix and plays an important biological function of interacting with different molecules and receptors. In this study, both odd- and even-numbered HA oligosaccharides (HAOs) with specific degrees of polymerization (DP) were prepared by different hydrochloric acid hydrolyses, and their structures were characterized by means of HPLC, ESI-MS, and NMR. The data show that the odd-numbered HAOs (DP3-11) have a glucuronic acid reducing end, while the even-numbered HAOs (DP2-10) have an N-acetylglucosamine reducing end. Biological evaluations indicated that all HAOs significantly inhibited the growth and migration of triple-negative breast cancer (TNBC) MDA-MB-231 cells. Among these oligosaccharides, the HA tetrasaccharide (DP4) was confirmed to be the minimum fragment necessary to inhibit MDA-MB-231 cells. Our data suggest that HAOs have potential value in the treatment of TNBC.
| S-EPMC6770828 | biostudies-literature
Project description:CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA), a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the-LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies.
| S-EPMC4574955 | biostudies-literature
Project description:Hyaluronic acid (HA) is an extracellular matrix molecule with multiple physical and biological functions found in many tissues, including cartilage. HA has been incorporated in a number of biomaterial and scaffold systems. However, HA in the material may be difficult to control if it is not chemically modified and chemical modification of HA may negatively impact biological function. In this study, we developed a poly(ethylene glycol) hydrogel with noncovalent HA-binding capabilities and evaluated its ability to support cartilage formation in vitro and in an articular defect model. Chondrogenic differentiation of mesenchymal stem cells encapsulated in the HA-interactive scaffolds containing various amounts of exogenous HA was evaluated. The HA-binding hydrogel without exogenous HA produced the best cartilage as determined by biochemical content (glysocaminoglycan and collagen), histology (Safranin O and type II collagen staining), and gene expression analysis for aggrecan, type I collagen, type II collagen, and sox-9. This HA-binding formulation was then translated to an osteochondral defect model in the rat knee. After 6 weeks, histological analysis demonstrated improved cartilage tissue production in defects treated with the HA-interactive hydrogel compared to noninteractive control scaffolds and untreated defects. In addition to the tissue repair in the defect space, the Safranin O staining in cartilage tissue surrounding the defect was greater in treatment groups where the HA-binding scaffold was applied. In sum, incorporation of a noncovalent HA-binding functionality into biomaterials provides an ability to interact with local or exogenous HA, which can then impact tissue remodeling and ultimately new tissue production.
| S-EPMC3501122 | biostudies-literature
Project description:Two specimens of human articulage were successively extracted with solutions of phosphate-buffered saline (PBS), 7 M-urea and 4 M-guanidine hydrochloride (Gdn-HCl). Proteoglycans from individual extracts were fractionated by DEAE-Sephacel chromatography and gel chromatography on Sephacryl S-400. The presence of three populations of large proteoglycans was demonstrated in all three extracts by composite agarose/polyacrylamide-gel electrophoresis (CAPAGE). The population corresponding to the fastest CAPAGE band of aggregating proteoglycans was shown to be extremely polydisperse, having Mr (as estimated by SDS/PAGE) decreasing continuously from more than 300,000 to the size corresponding to 'free' hyaluronic acid-binding region (HABR) (about 70,000). A rather polydisperse set of HABR-containing fragments which spanned a broad range of sizes, and also differed in their keratan sulphate contents, was isolated from both 7 M-urea and 4 M-Gdn-HCl extracts. PBS and 7 M-urea extracts, but not the Gdn-HCl extract, further contained small proteoglycans, identified as fast-migrating bands on CAPAGE electrophoretograms. One of those small species was recognized with an antibody against the small proteoglycan PG II; the other two remain to be positively identified. However, the glycosaminoglycan of the small species which was present exclusively in the PBS extract was identified as keratan sulphate; this species may thus belong to the family of small keratan sulphate-containing proteolygans.
| S-EPMC1149802 | biostudies-other
Project description:Myocardial infarction (MI) is identified as one of the major causes of mortality and disability worldwide. For severe myocardial infarction, even advanced forms of clinical intervention often lead to unsatisfactory therapeutic results. Thus, alternative strategies for MI treatment are still desirable. Previously studies reported the capacity of degradative fragment of h-HA (high molecular weight hyaluronic acid), hyaluronan oligosaccharides (<10 disaccharides units, o-HA), for wound healing by influence on angiogenesis, inspiring us to study its potential for myocardial functional recovery against MI. However, there are few reports about o-HA in MI therapy. Methods: In our study, we synthesized o-HA with 6~10 disaccharides (4-5 kDa) by enzymatic degradation and investigated its therapeutic effects on MI. Results: We found that o-HA could reduce infarct size and apoptosis in MI region, also promote myocardial angiogenesis and myocardial function reconstruction in MI mouse model. Furthermore, our results also indicated that o-HA in cardiac improved polarization of M2 type macrophage, removed the inflammatory response caused by neutrophil for accelerating myocardial function reconstruction in vivo. The transcriptomic analyses revealed that o-HA could activate expression of chemokines Ccl2 and Cxcl5 for promoting macrophage polarization and stimulate MAPK and JAK/STAT signaling pathway for compensatory response of myocardial function. Conclusion: Collectively, our results suggested o-HA with 6~10 disaccharides might be a potential agent for reconstruction of cardiac function against MI.
| S-EPMC6485288 | biostudies-literature
Project description:Binding of exogenous [35S]sulphate-labelled cartilage proteoglycans to cells was studied with suspension cultures of calf articular-cartilage chondrocytes. Proteoglycans interact with hyaluronic acid at the cell surface via their hyaluronic acid-binding region. The binding is time-dependent and saturable, but does not appear to be freely reversible. The bound 35S-labelled proteoglycans are located at the cell surface, and only small proportions of the proteoglycans are internalized.
| S-EPMC1152315 | biostudies-other
Project description:Persistently high plasma levels of serum amyloid A (SAA) may induce AA amyloidosis in various organs causing their dysfunction. Although SAA isoforms share a high degree of homology, only the SAA1.1 isoform is found in amyloid deposits. SAA1.1 misfolding is a nucleation-dependent process with dimer and trimer formation playing a major role in SAA fibril formation through self-catalyzed recruitment of native SAA molecules. Yet, a structural model of initial SAA oligomerization is still missing. In this study, we constructed a loosely associated model for murine SAA1.1 and SAA2.2 dimers in the presence or absence of hyaluronic acid as an exemplary glycosaminoglycan, a factor known to facilitate SAA fibril formation. Molecular dynamics simulations predicted that hyaluronic acid finally stabilized in a different binding pocket of the pathogenic SAA1.1 dimer compared to the nonpathogenic SAA2.2 dimer. Besides, Markov state modeling points to dynamic behavioral differences between the linker region of SAA1.1 and SAA2.2 and identifies a state unique to pathogenic SAA1.1 while bound to hyaluronic acid. The presence or absence of hyaluronic acid, as well as the dimer interface switch, affects dynamic behavior and possible oligomeric states, proposing a conceivable clue to the deviant pathogenicity of the two SAA isoforms.
| S-EPMC6704436 | biostudies-literature
Project description:Both cell adhesion protein CD44 and its main ligand hyaluronic acid (HA) are thought to be involved in several processes ultimately requiring cytoskeleton rearrangements. Here, we show that the small guanine nucleotide (GTP)-binding protein, Rac1, can be activated upon HA binding to CD44. When applied locally to a passive cell edge, HA promoted the formation of lamellipodial protrusions in the direction of the stimulus. This process was inhibited by the prior injection of cells with dominant-negative N17Rac recombinant protein or by pretreatment of cells with monoclonal anti-CD44 antibodies, interfering with HA binding, implying the direct involvement of CD44 in signaling to Rac1.
| S-EPMC2174315 | biostudies-literature