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Glycoconjugate Journal Dec 2016Sulfatases that specifically catalyze the hydrolysis of the sulfate groups on chondroitin sulfate (CS)/dermatan sulfate (DS) poly- and oligosaccharides belong to the... (Review)
Review
Sulfatases that specifically catalyze the hydrolysis of the sulfate groups on chondroitin sulfate (CS)/dermatan sulfate (DS) poly- and oligosaccharides belong to the formylglycine-dependent family of sulfatases and have been widely found in various mammalian and bacterial organisms. However, only a few types of CS/DS sulfatase have been identified so far. Recently, several novel CS/DS sulfatases have been cloned and characterized. Advanced studies have provided significant insight into the biological function and mechanism of action of CS/DS sulfatases. Moreover, further studies will provide powerful tools for structural and functional studies of CS/DS as well as related applications. This article reviews the recent progress in CS/DS sulfatase research and is expected to initiate further research in this field.
Topics: Animals; Bacteria; Bacterial Proteins; Chondroitin Sulfates; Dermatan Sulfate; Humans; Structure-Activity Relationship; Sulfatases
PubMed: 27526113
DOI: 10.1007/s10719-016-9720-0 -
Glycobiology Sep 2002Glycosaminoglycans constitute a considerable fraction of the glycoconjugates found on cellular membranes and in the extracellular matrix of virtually all mammalian... (Review)
Review
Glycosaminoglycans constitute a considerable fraction of the glycoconjugates found on cellular membranes and in the extracellular matrix of virtually all mammalian tissues. Their ability to bind and alter protein-protein interactions or enzymatic activity has identified them as important determinants of cellular responsiveness in development, homeostasis, and disease. Although heparan sulfate tends to be emphasized as the most biologically active glycosaminoglycan, dermatan sulfate is a particularly attractive subject for further study because it is expressed in many mammalian tissues and it is the predominant glycan present in skin. Dermatan and dermatan sulfate proteoglycans have also been implicated in cardiovascular disease, tumorigenesis, infection, wound repair, and fibrosis. Growing evidence suggests that this glycosaminoglycan, like the better studied heparin and heparan sulfate, is an important cofactor in a variety of cell behaviors.
Topics: Blood Coagulation; Carbohydrate Sequence; Dermatan Sulfate; Extracellular Matrix; Growth Substances; Humans; Molecular Sequence Data; Molecular Structure; Wound Healing
PubMed: 12213784
DOI: 10.1093/glycob/cwf066 -
IUBMB Life Oct 2002Chondroitin sulfate and dermatan sulfate are synthesized as galactosaminoglycan polymers containing N-acetylgalactosmine alternating with glucuronic acid. The sugar... (Review)
Review
Chondroitin sulfate and dermatan sulfate are synthesized as galactosaminoglycan polymers containing N-acetylgalactosmine alternating with glucuronic acid. The sugar residues are sulfated to varying degrees and positions depending upon the tissue sources and varying conditions of formation. Epimerization of any of the glucuronic acid residues to iduronic acid at the polymer level constitutes the formation of dermatan sulfate. Chondroitin/dermatan glycosaminoglycans are covalently attached by a common tetrasaccharide sequence to the serine residues of core proteins while they are adherent to the inner surface of endoplasmic reticulum/Golgi vesicles. Addition of the first sugar residue, xylose, to core proteins begins in the endoplasmic reticulum, followed by the addition of two galactose residues by two distinct glycosyl transferases in the early cis/medial regions of the Golgi. The linkage tetrasaccharide is completed in the medial/trans Golgi by the addition of the first glucuronic acid residue, followed by transfer of N-acetylgalactosamine to initiate the formation of a galactosaminoglycan rather than a glucosaminoglycan. This specific N-acetylgalactosaminyl transferase is different from the chondroitin synthase involved in generation of the repeating disaccharide units to form the chondroitin polymer. Sulfation of the chondroitin polymer by specific sulfotransferases occurs as the polymer is being formed. All the enzymes in the pathway for synthesis have been cloned, with the exception of the glucuronyl to iduronyl epimerase involved in the formation of dermatan residues.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Humans
PubMed: 12512856
DOI: 10.1080/15216540214923 -
General Pharmacology May 19951. Dermatan sulfate is a linear, sulfated polysaccharide and is a glycosaminoglycan component of several important proteoglycans. This minireview discusses the... (Review)
Review
1. Dermatan sulfate is a linear, sulfated polysaccharide and is a glycosaminoglycan component of several important proteoglycans. This minireview discusses the biosynthesis, structure and biological function of dermatan sulfate proteoglycans. 2. Dermatan sulfate and its derivatives are being investigated as a new class of anticoagulant and antithrombotic agents. 3. The preparation, chemistry and structure-activity relationship of dermatan sulfate is described. 4. Dermatan sulfate, low molecular weight dermatan sulfate and glycosaminoglycan mixtures containing dermatan sulfate have been used clinically. 5. The future prospects of these agents and other new, potentially useful dermatan sulfate based therapeutics are discussed.
Topics: Animals; Dermatan Sulfate; Humans
PubMed: 7789716
DOI: 10.1016/0306-3623(94)00231-b -
PLoS Genetics Feb 2022Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their...
Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their biosynthesis have made CS/DS function a challenging problem to study genetically. In our study, we generated loss-of-function alleles in zebrafish genes encoding CS/DS biosynthetic enzymes and characterized the effect on development in single and double mutants. Homozygous mutants in chsy1, csgalnact1a, csgalnat2, chpfa, ust and chst7, respectively, develop to adults. However, csgalnact1a-/- fish develop distinct craniofacial defects while the chsy1-/- skeletal phenotype is milder and the remaining mutants display no gross morphological abnormalities. These results suggest a high redundancy for the CS/DS biosynthetic enzymes and to further reduce CS/DS biosynthesis we combined mutant alleles. The craniofacial phenotype is further enhanced in csgalnact1a-/-;chsy1-/- adults and csgalnact1a-/-;csgalnact2-/- larvae. While csgalnact1a-/-;csgalnact2-/- was the most affected allele combination in our study, CS/DS is still not completely abolished. Transcriptome analysis of chsy1-/-, csgalnact1a-/- and csgalnact1a-/-;csgalnact2-/- larvae revealed that the expression had changed in a similar way in the three mutant lines but no differential expression was found in any of fifty GAG biosynthesis enzymes identified. Thus, zebrafish larvae do not increase transcription of GAG biosynthesis genes as a consequence of decreased CS/DS biosynthesis. The new zebrafish lines develop phenotypes similar to clinical characteristics of several human congenital disorders making the mutants potentially useful to study disease mechanisms and treatment.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Glycosyltransferases; Phenotype; Zebrafish
PubMed: 35192612
DOI: 10.1371/journal.pgen.1010067 -
Current Opinion in Structural Biology Oct 2015Recent functional studies on chondroitin sulfate-dermatan sulfate (CS-DS) demonstrated its indispensable roles in various biological events including brain development... (Review)
Review
Recent functional studies on chondroitin sulfate-dermatan sulfate (CS-DS) demonstrated its indispensable roles in various biological events including brain development and cancer. CS-DS proteoglycans exert their physiological activity through interactions with specific proteins including growth factors, cell surface receptors, and matrix proteins. The characterization of these interactions is essential for regulating the biological functions of CS-DS proteoglycans. Although amino acid sequences on the bioactive proteins required for these interactions have already been elucidated, the specific saccharide sequences involved in the binding of CS-DS to target proteins have not yet been sufficiently identified. In this review, recent findings are described on the interaction between CS-DS and some proteins which are especially involved in the central nervous system and cancer development/metastasis.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Extracellular Matrix Proteins; Humans; Intercellular Signaling Peptides and Proteins; Neoplasm Metastasis; Neoplasms; Neuronal Plasticity; Neurons; Protein Binding; Receptor for Advanced Glycation End Products; Receptors, Cell Surface; Wnt Signaling Pathway
PubMed: 26164146
DOI: 10.1016/j.sbi.2015.06.004 -
Advances in Experimental Medicine and... 1995Variable substitutions and locations of the sulfate esters along the backbone of chondroitin/dermatan sulfate chains, combined with their carbohydrate structures,... (Review)
Review
Variable substitutions and locations of the sulfate esters along the backbone of chondroitin/dermatan sulfate chains, combined with their carbohydrate structures, present topographies to immune systems which can be recognized as antigenic. This has led to the development of a number of monoclonal antibodies which recognize distinct epitopes in the native structures of these glycosaminoglycan chains. In some studies, the original chondroitin/dermatan sulfate proteoglycan was digested with chondroitinase enzymes before being used as an immunogen. in this case, the linkage oligosaccharides remaining bound to the core protein contain a modified (4,5-unsaturated) hexuronic acid derivative at their non-reducing ends as a result of the eliminase mechanism of the enzyme. This 'haptenic' structure is highly antigenic and has led to the development of a number of monoclonal antibodies which recognize this structure as part of their epitopes. Examples of the use of some of these monoclonal antibodies for localization of proteoglycan structures in tissue sections and on transblots are described. The precise structures are known for only a few of the native epitopes recognized by these monoclonal antibodies. Recent analytical methods have been developed for determining structures of chondroitin sulfate oligosaccharides. An example of the use of these methods to analyze the structures of the non-reducing termini of chondroitin/dermatan sulfate chains is discussed. The results show their potential value for quantifying the native epitope recognized by a monoclonal antibody, designated 3B3, which recognizes chains terminated by glucuronic acid-N-acetylgalactosamine-6-sulfate. Such methods should be useful for determining the epitope structures for other monoclonal antibodies in this class.
Topics: Antibodies, Monoclonal; Antibody Specificity; Antigens; Carbohydrate Sequence; Chondroitin Sulfates; Dermatan Sulfate; Epitopes; Humans; Molecular Sequence Data; Molecular Structure
PubMed: 8597249
DOI: 10.1007/978-1-4615-1885-3_21 -
Food & Function Jan 2022The objective of the present study was to explore the desensitization effect of dermatan sulfate (DS) and chondroitin sulfate (CS) from () on mice sensitized by major...
The objective of the present study was to explore the desensitization effect of dermatan sulfate (DS) and chondroitin sulfate (CS) from () on mice sensitized by major royal jelly protein 1 (MRJP1). First, the affinity between six glycosaminoglycans and the MRJP1 polyclonal antibody was measured by the ELISA method. dermatan sulfate ( DS) and chondroitin sulfate ( CS) were selected due to their highest binding affinity. Second, the molecular docking method was used to explore the interaction between DS and MRJP1 and CS and MRJP1. The results showed that DS and CS combined with MRJP1 successfully, which meant a potential function of relieving the MRJP1-caused allergy. Finally, the MRJP1-sensitized mice model was established and confirmed that DS and CS had the desensitization ability to relieve MRJP1-induced allergic symptoms. To validate the conclusion, the relief of allergic symptoms in mice was observed. The production of total IgE, MRJP1-specific IgE and histamine was measured. The desensitization mechanism was further studied by measuring cytokines (IL-4 and IFN-γ) from splenocytes stimulated with MRJP1 . Based on and experiments, it was confirmed that DS and CS have the ability to alleviate MRJP1-induced allergic symptoms, which proposes a potential candidate material against IgE-mediated food allergy.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Female; Fishes; Food Hypersensitivity; Glycoproteins; Insect Proteins; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Rabbits
PubMed: 34919100
DOI: 10.1039/d1fo03244e -
Current Drug Discovery Technologies Dec 2008Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral... (Review)
Review
Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral infections. Major GAGs include heparin (Hep)/heparan sulfate, and chondroitin sulfate (CS)/dermatan sulfate (DS). Hep has been used for the treatment of thromboembolic disorders for more than 75 years, and has an established position in therapy today. CS/DS has attracted less attention and its clinical use is limited. However, CS/DS also have intriguing biological activities, which in turn should help in the development of CS/DS-based therapeutics. In this review, the following potential applications of CS/DS chains are discussed. (1) Sugar drugs for parasitic and viral infections. Particular CS variants appear to be involved in infections of various microbes, suggesting that CS/DS oligosaccharide sequences specifically interacting with microbes will lead to the development of inhibitory drugs for these infections. (2) Regenerative medicine. Biological activities of CS/DS chains possibly involve various growth factors, also known as Hep-binding growth factors. Specific CS/DS chains recruit growth/neurotrophic factors and/or potentiate their activities, suggesting that minute amounts of functional CS/DS chains can be utilized for tissue regeneration instead of signaling proteins. (3) Anti-tumor drugs. Specific saccharide structures in CS/DS chains appear to be involved in tumor cell proliferation and metastasis. The detection and identification of such CS/DS saccharide sequences would be an important contribution to cancer therapy.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Chondroitin Sulfates; Dermatan Sulfate; Drug Discovery; Glycosaminoglycans; Humans; Infections; Liver Regeneration; Neoplasms; Neurodegenerative Diseases; Osteoarthritis
PubMed: 19075609
DOI: 10.2174/157016308786733564 -
Carbohydrate Research Sep 2023Dermatan sulfate is one of the major glycosaminoglycan (GAG) present in the animal hides, which is a waste/byproduct from meat industry. Efficient utilization of these...
Dermatan sulfate is one of the major glycosaminoglycan (GAG) present in the animal hides, which is a waste/byproduct from meat industry. Efficient utilization of these meat industry wastes is garnering attention because these wastes render a possibility for their conversion into useful products. With the increased concerns over health, various initiatives have been developed to permit more efficient utilization of these by-products and thereby directly impacting environmental sustainability. Herein, we demonstrate for the first time an efficient and environmentally safe ionic liquid-assisted enzymatic process for the extraction of dermatan sulfate from buffalo hides. Dermatan sulfate has been extracted, separated, and purified from the GAG mixture using IL-assisted enzymatic digestions and chromatographic separations. NMR, FT-IR, and ESI-MS measurements showed typical characteristic peaks for dermatan sulfate. The advantages of this eco-friendly process adopted include i) use of fewer chemicals, ii) elimination of harsh chemicals, iii) elimination of various steps and sub-steps, iv) reduction in process time (12 h), and v) increase in extraction yield by 75% when compared to conventional enzymatic process (57%). Thus, the use of ionic liquids alongside enzymes will serve as an efficient methodology for the futuristic development of these derived GAGs for their potential applications.
Topics: Animals; Dermatan Sulfate; Ionic Liquids; Spectroscopy, Fourier Transform Infrared; Glycosaminoglycans; Digestion
PubMed: 37441844
DOI: 10.1016/j.carres.2023.108897