Characterization of structural motifs for interactions between glycosaminoglycans and proteins

Yang, Jiyuan

doi:10.1016/j.carres.2017.10.008

Cited by 25 publications

(25 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Routine analysis of the GAG chains in PGs typically involves compositional and disaccharide analysis, mapping of 4-8 oligosaccharide segments and occasionally domain analysis; however, extensive sequencing is not normally undertaken. [55,88,90,91] [87,88] Embedded sulphation motifs such as CS-D and CS-E internally in the CS chains have growth factor interactive properties, the surrounding regions of the CS chain serve a carrier function for these biological motifs.…”

Section: Gag Heterogeneity and Complexity Confer Inherent Difficultiementioning

confidence: 99%

“…Inhibits amyloid-β induced brain endothelial cell toxicity restoring angiogenesis viii. [91] All five domains of perlecan have been recombinantly produced and these fragments have been shown to retain the interactive properties of the native molecule ( Table 2). Induction of VEGF in brain endothelial cells integrin α5β1 and ERK signaling x. Upregulated in human brain arteriovenous malformation mediating VEGF effects xi.…”

Section: Recombinant Proteoglycansmentioning

confidence: 99%

See 1 more Smart Citation

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Hayes

Melrose

2019

Advanced Therapeutics

View full text Add to dashboard Cite

The aim of this study is to review developments in glycosaminoglycan and proteoglycan research relevant to cartilage repair biology and in particular the treatment of osteoarthritis (OA). Glycosaminoglycans decorate a diverse range of extracellular matrix and cell associated proteoglycans conveying structural organization and physico-chemical properties to tissues. They play key roles mediating cellular interactions with bioactive growth factors, cytokines, and morphogenetic proteins, and structural fibrillar collagens, cell interactive and extracellular matrix proteoglycans, and glycoproteins which define tissue function. Proteoglycan degradation detrimentally affects tissue functional properties. Therapeutic strategies have been developed to counter these degenerative changes. Neo-proteoglycans prepared from chondroitin sulfate or hyaluronan and hyaluronan or collagen-binding peptides emulate the interactive, water imbibing, weight bearing, and surface lubricative properties of native proteoglycans. Many neo-proteoglycans outperform native proteoglycans in terms of water imbibition, matrix stabilization, and resistance to proteolytic degradation. The biospecificity of recombinant proteoglycans however, provides precise attachment to native target molecules. Visco-supplements augmented with growth factors/therapeutic cells, hyaluronan, and lubricin (orthobiologicals) have the capacity to lubricate and protect cartilage, control inflammation, and promote cartilage repair and regeneration of early cartilage lesions and may represent a more effective therapeutic approach to the treatment of mild to moderate OA and deserve further study.Similar protective perineural net structures assembled from the lectican proteoglycan family and HA also occur in the CNS/PNS. These so called perineuronal nets are visualized by immunolocalization of MAb 1B5 (+) epitope in rat brain (e) and pericellular 1B5(+) epitope expression by isolated neurons (f). Scale bars 100 µm.

show abstract

Section: Gag Heterogeneity and Complexity Confer Inherent Difficultiementioning

confidence: 99%

Section: Recombinant Proteoglycansmentioning

confidence: 99%

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Hayes

Melrose

2019

Advanced Therapeutics

View full text Add to dashboard Cite

show abstract

“…The ECM seems to be a natural drug sustained release system for proteins. Yang [10] have shown that the interaction between proteins and glycosaminoglycan (GAG) is mainly mediated by the charge adsorption between the amino group on the protein and the sulfonic acid or carboxyl group on the glycosaminoglycan molecule. The binding of GAG and proteins can effectively regulate the release rate of proteins and prevent proteolytic degradation of proteins in tissue fluids [11].…”

Section: Introductionmentioning

confidence: 99%

ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis

Cao

Han

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Intra-articular injection of anti-inflammatory drugs can be a promising strategy for recovery of injured articular cartilage. We prepared a series of injectable thermo-sensitive composite hydrogels, composed of Pluronic F127, glycosaminoglycan (GAG) and bone morphogenetic protein (BMP-2), which was designed to mimic extracellular matrix (ECM). The rheological properties and dissolution rate of composite hydrogels containing chondroitin sulfate or with different hyaluronic acid molecular mass (10k, 90k, 800k) were investigated. Meanwhile, bovine serum albumin (BSA) or FITC-BSA was chosen as model drug loaded into PF/GAG hydrogels to study their sustained release behavior in vitro. The results showed that hydrogels could maintain shapes for more than 16 days and the release rate of BSA in PF/GAG composite gels was much slower than in PF127 gels, due to the affinity between BSA and GAG. Furthermore, increasing the molecular weight of hyaluronic acid correspondingly increased hydrogel dissolution rate and BSA release in the hydrogels. Subsequently, MTT experiments were performed to investigate the toxicity of the hydrogels on mouse pre-osteoblast cell MC3T3-E1. In vivo anti-inflammation results showed that PF/GAG@BMP-2 composite hydrogels had the most efficient efficacy on recovery of injured cartilage, which is induced by osteoarthritis, compared to the control groups (PF127@BMP-2 or BMP-2 saline solution).

show abstract

“…Molecular docking of 3D-model of BTH [15] with C H dimers and trimers (nonsulfatated GAG ([--4) GlcA(β1-) GalNAc (β1--] n, where n is 2 or 3, respectively [19]) has revealed 8 binding sites/positions for these ligands on the enzyme surface (Figure 1). These sites are quite similar but not identical to the binding sites for CHS trimer and HP tetramer [14].…”

Section: Resultsmentioning

confidence: 99%

“…nih. gov using dimer and trimer ([--4) GlcA(β1-3) GalNAc(β1--] n ), where n is equal to 2 or 3, respectively [19]). CH docking on BTH molecule surface (a mixture of 10 dimers and 10 trimers per BHT molecule) was run 100 times at рН 7.…”

Section: Calculationsmentioning

confidence: 99%

Thermostabilization of Hyaluronidase by Chondroitin Ligands in Molecular Docking

Maksimenko¹

2019

CCR

View full text Add to dashboard Cite

Speedup of present high-molecular drug derivatives developments is based on the computational methods harmonic application. Such glycosidase as hyaluronidase has been functionated among multifarious glycosaminoglycan microenvironment in blood circulation of organism. It is important for elucidation of action mechanism of biosystem components (on vascular wall) and productive obtaining of hyaluronidase derivatives of cardiological destination the using of computer aided calculations for investigation of protein-glycosaminoglycan interactions. The aim of our study became the molecular docking fulfillment for 3D model of bovine testicular hyaluronidase with short-chain dimer and trimer chondroitin ligands. We used the molecular docking of hyaluronidase with chondroitin ligands for theoretical determination of biocatalyst conformational stability. At temperatures higher than 300 K free/native hyaluronidase (without ligands) displayed conformational transitions leading to its inactivation. Predominant manifestation of these transitions was an irreversible attraction developing between the protein area proximate to Glu-105, on the one hand, and to Arg-59 and Arg-96, on the other. Lowering of temperature did not restore the initial 3D structure of hyaluronidase. Binding of chondroitin ligands at ch 6, ch 3 and ch 1 sites stabilized the enzyme, increasing its denaturation temperature by 10°C. The highest degree of stabilization was achieved after chondroitin binding to ch 6. This effect was higher than that for chondroitin sulfate trimers concerning the enzyme inhibition by heparin tetramer, which requires binding of 4-5 chondroitin sulfate ligands to the enzyme surface. Molecular docking of 3D model of bovine testicular hyaluronidase with chondroitin dimers and trimers has revealed eight sites for their binding to the enzyme surface. At biological concentrations of these ligands the most important binding sites for them are ch 6, ch 3 and ch 1. Binding at these sites induces a reversible deformation of the protein 3D structure. Interactions between 3D model of bovine hyaluronidase with chondroitin ligands are based predominantly on electrostatic forces. Chondroitin ligands stabilized 3D structure of hyaluronidase after binding predominantly at chondroitin 6 as well as chondroitin 3 and chondroitin 1 positions and their effect was higher than chondroitin sulfate upon enzyme inhibition by heparin tetramer. Stabilizing effects of chondroitin and chondroitin sulfate ligands are fundamental for further direct theoretical comparative investigation of impact produced by these ligands.

show abstract

Characterization of structural motifs for interactions between glycosaminoglycans and proteins

Cited by 25 publications

References 65 publications

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis

Thermostabilization of Hyaluronidase by Chondroitin Ligands in Molecular Docking

Contact Info

Product

Resources

About