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Methods in Molecular Biology (Clifton,... 2022Chemical protein synthesis has achieved tremendous progress in the past decades. With the development of chemical ligation as powerful tools, the scope of synthetic...
Chemical protein synthesis has achieved tremendous progress in the past decades. With the development of chemical ligation as powerful tools, the scope of synthetic protein is greatly expanded. Proteoglycans are a class of sulfated glycoproteins widely distributed on the cell surface and in the extracellular matrix, which are extensively engaged in cellular communication events. Consisting of protein backbone and glycosaminoglycan(s) side chain, proteoglycans are highly complex and heterogeneous in nature. Chemical synthesis provides facile and reliable approach to these molecules, with defined glycan structure and sulfation pattern. One remaining problem is that the acid-labile sulfates could hardly survive during the typical solid phase peptide synthesis (SPPS) process. In this chapter, strategic design of a "glycopeptide cassette" for the preparation of sulfated glycoprotein is described. In particular, we provide protocols for the chemical synthesis of ectodomain fragment (23-120) of sulfated glycoprotein syndecan-1.
Topics: Glycopeptides; Glycosaminoglycans; Heparitin Sulfate; Polysaccharides; Proteoglycans; Sulfates
PubMed: 35761038
DOI: 10.1007/978-1-0716-2489-0_1 -
The Journal of Biological Chemistry Aug 2019Sulfur is present in the amino acids cysteine and methionine and in a large range of essential coenzymes and cofactors and is therefore essential for all organisms. It... (Review)
Review
Sulfur is present in the amino acids cysteine and methionine and in a large range of essential coenzymes and cofactors and is therefore essential for all organisms. It is also a constituent of sulfate esters in proteins, carbohydrates, and numerous cellular metabolites. The sulfation and desulfation reactions modifying a variety of different substrates are commonly known as sulfation pathways. Although relatively little is known about the function of most sulfated metabolites, the synthesis of activated sulfate used in sulfation pathways is essential in both animal and plant kingdoms. In humans, mutations in the genes encoding the sulfation pathway enzymes underlie a number of developmental aberrations, and in flies and worms, their loss-of-function is fatal. In plants, a lower capacity for synthesizing activated sulfate for sulfation reactions results in dwarfism, and a complete loss of activated sulfate synthesis is also lethal. Here, we review the similarities and differences in sulfation pathways and associated processes in animals and plants, and we point out how they diverge from bacteria and yeast. We highlight the open questions concerning localization, regulation, and importance of sulfation pathways in both kingdoms and the ways in which findings from these "red" and "green" experimental systems may help reciprocally address questions specific to each of the systems.
Topics: Animals; Humans; Plants; Sulfates; Sulfur
PubMed: 31270211
DOI: 10.1074/jbc.REV119.007422 -
Journal of Experimental Botany Aug 2019Sulfated peptides are plant hormones that are active at nanomolar concentrations. The sulfation at one or more tyrosine residues is catalysed by tyrosylprotein... (Review)
Review
Sulfated peptides are plant hormones that are active at nanomolar concentrations. The sulfation at one or more tyrosine residues is catalysed by tyrosylprotein sulfotransferase (TPST), which is encoded by a single-copy gene. The sulfate group is provided by the co-substrate 3´-phosphoadenosine 5´-phosphosulfate (PAPS), which links synthesis of sulfated signaling peptides to sulfur metabolism. The precursor proteins share a conserved DY-motif that is implicated in specifying tyrosine sulfation. Several sulfated peptides undergo additional modification such as hydroxylation of proline and glycosylation of hydroxyproline. The modifications render the secreted signaling molecules active and stable. Several sulfated signaling peptides have been shown to be perceived by leucine-rich repeat receptor-like kinases (LRR-RLKs) but have signaling pathways that, for the most part, are yet to be elucidated. Sulfated peptide hormones regulate growth and a wide variety of developmental processes, and intricately modulate immunity to pathogens. While basic research on sulfated peptides has made steady progress, their potential in agricultural and pharmaceutical applications has yet to be explored.
Topics: Peptide Hormones; Plant Development; Plant Growth Regulators; Plant Proteins; Plants; Sulfates
PubMed: 31231771
DOI: 10.1093/jxb/erz292 -
Marine Drugs Sep 2019The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene... (Review)
Review
The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene aliphatic sulfates are considerably rarer with examples being reported from a diverse array of organisms including echinoderms, sponges and ascidians. While no ecological roles for these metabolites have been proposed, they do exhibit a diverse array of biological activities including thrombin inhibition; the ability to induce metamorphosis in larvae; antiproliferative, antibacterial and antifungal properties; and metalloproteinase inhibition. Of particular interest and an avenue for future development is the finding of antifouling properties with low or nontoxic effects to the environment. This review focuses on alkyl sulfates and related sulfamates, their structures and biological activities. Spectroscopic and spectrometric techniques that can be used to recognize the presence of sulfate groups are also discussed, data for which will enhance the ability of researchers to recognize this class of chemically- and biologically-interesting marine natural products.
Topics: Animals; Antifungal Agents; Aquatic Organisms; Biological Products; Echinodermata; Humans; Invertebrates; Larva; Sulfates; Urochordata
PubMed: 31505775
DOI: 10.3390/md17090527 -
Acta Pharmacologica Sinica Feb 2021Forsythin extracted from Forsythiae Fructus is widely used to treat fever caused by the common cold or influenza in China, Japan and Korea. The present study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Forsythin extracted from Forsythiae Fructus is widely used to treat fever caused by the common cold or influenza in China, Japan and Korea. The present study aimed to analyze the pharmacokinetics, metabolism and excretion routes of forsythin in humans and determine the major enzymes and transporters involved in these processes. After a single oral administration, forsythin underwent extensive metabolism via hydrolysis and further sulfation. In total, 3 of the 13 metabolites were confirmed by comparison to reference substances, i.e., aglycone M1, M1 sulfate (M2), and M1 glucuronide (M7). Hydrolysis was the initial and main metabolic pathway of the parent compound, followed by extensive sulfation to form M2 and a reduced level of glucuronidation to form M7. In addition, the plasma exposure of M2 and M7 were 86- and 4.2-fold higher than that of forsythin. Within 48 h, ~75.1% of the administered dose was found in urine, with M2 accounting for 71.6%. Further phenotyping experiments revealed that sulfotransferase 1A1 and UDP-glucuronosyltransferase 1A8 were the most active hepatic enzymes involved in the formation of M2 and M7, respectively. The in vitro kinetic study provided direct evidence that M1 showed a preference for sulfation. Sulfated conjugate M2 was identified as a specific substrate of organic anion transporter 3, which could facilitate the renal excretion of M2. Altogether, our study demonstrated that sulfation dominated the metabolism and pharmacokinetics of forsythin, while the sulfate conjugate was excreted mainly in the urine.
Topics: Administration, Oral; Double-Blind Method; Female; Glucosides; Glucuronides; HEK293 Cells; Humans; Male; Organic Anion Transporters, Sodium-Independent; Sulfates
PubMed: 32860005
DOI: 10.1038/s41401-020-0481-8 -
Cells Dec 2021Hydrogels are commonly used for the 3D culture of musculoskeletal cells. Sulfated hydrogels, which have seen a growing interest over the past years, provide a... (Review)
Review
Hydrogels are commonly used for the 3D culture of musculoskeletal cells. Sulfated hydrogels, which have seen a growing interest over the past years, provide a microenvironment that help maintain the phenotype of chondrocytes and chondrocyte-like cells and can be used for sustained delivery of growth factors and other drugs. Sulfated hydrogels are hence valuable tools to improve cartilage and intervertebral disc tissue engineering. To further advance the utilization of these hydrogels, we identify and summarize the current knowledge about different sulfated hydrogels, highlight their beneficial effects in cartilage and disc research, and review the biofabrication processes most suitable to secure best quality assurance through deposition fidelity, repeatability, and attainment of biocompatible morphologies.
Topics: Animals; Cartilage; Humans; Hydrogels; Intervertebral Disc; Research; Sulfates; Tissue Engineering
PubMed: 34944076
DOI: 10.3390/cells10123568 -
IUBMB Life Oct 2007Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a... (Review)
Review
Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. An important issue is whether the human body is equipped with mechanisms to counteract the potentially harmful effects of nitrotyrosine. Sulfate conjugation, as mediated by the cytosolic sulfotransferases (SULTs), is widely used for the biotransformation and disposal of a variety of drugs and other xenobiotics, as well as endogenous thyroid/steroid hormones and catecholamine neurotransmitters. Recent studies have revealed that the sulfation of nitrotyrosine occurs in cells under oxidative/nitrative stress, and have pinpointed the SULT1A3 as the responsible SULT enzyme. In this review, we summarized the available information concerning the biochemistry of nitrotyrosine sulfation and the effects of genetic polymorphisms on the nitrotyrosine sulfating activity of SULT1A3. Functional implications of the sulfation of nitrotyrosine are discussed.
Topics: Animals; Arylsulfotransferase; Humans; Sulfates; Sulfotransferases; Tyrosine
PubMed: 17891604
DOI: 10.1080/15216540701589320 -
Marine Drugs Jun 2022Fucoidans encompass versatile and heterogeneous sulfated biopolysaccharides of marine origin, specifically brown algae and marine invertebrates. Their chemistry and... (Review)
Review
Fucoidans encompass versatile and heterogeneous sulfated biopolysaccharides of marine origin, specifically brown algae and marine invertebrates. Their chemistry and bioactivities have been extensively investigated in the last few decades. The reported studies revealed diverse chemical skeletons in which l-fucose is the main sugar monomer. However, other sugars, i.e., galactose, mannose, etc., have been identified to be interspersed, forming several heteropolymers, including galactofucans/fucogalactans (G-fucoidans). Particularly, sulfated galactofucans are associated with rich chemistry contributing to more promising bioactivities than fucans and other marine polysaccharides. The previous reports in the last 20 years showed that G-fucoidans derived from were the most studied; 21 bioactivities were investigated, especially antitumor and antiviral activities, and unique biomedical applications compared to other marine polysaccharides were demonstrated. Hence, the current article specifically reviews the biogenic sources, chemistry, and outstanding bioactivities of G-fucoidans providing the opportunity to discover novel drug candidates.
Topics: Fucose; Galactose; Phaeophyceae; Polysaccharides; Sulfates
PubMed: 35877705
DOI: 10.3390/md20070412 -
Bone Oct 2023Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter...
Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses. Moreover, the N-terminal fragment of collagen X, known as collagen X marker (CXM), is considered a real-time marker of endochondral ossification and growth velocity and was studied in individuals with achondroplasia and osteogenesis imperfecta. In this work, urinary GAG sulfation and blood CXM levels were investigated as potential biomarkers for individuals affected by DTD. Chondroitin sulfate disaccharide analysis was performed on GAGs isolated from urine by HPLC after GAG digestion with chondroitinase ABC and ACII, while CXM was assessed in dried blood spots. Results from DTD patients were compared with an age-matched control population. Undersulfation of urinary GAGs was observed in DTD patients with some relationship to the clinical severity and underlying SLC26A2 variants. Lower than normal CXM levels were observed in most patients, even if the marker did not show a clear pattern in our small patient cohort because CXM values are highly dependent on age, gender and growth velocity. In summary, both non-invasive biomarkers are promising assays targeting various aspects of the disorder including overall metabolism of sulfated GAGs and endochondral ossification.
Topics: Animals; Anion Transport Proteins; Sulfate Transporters; Achondroplasia; Glycosaminoglycans; Biomarkers; Collagen; Sulfates
PubMed: 37454964
DOI: 10.1016/j.bone.2023.116838 -
Analytical and Bioanalytical Chemistry Jan 2020Glycosaminoglycans (GAGs) are a physio- and pharmacologically highly relevant class of complex saccharides, possessing a linear sequence and strongly acidic character....
Glycosaminoglycans (GAGs) are a physio- and pharmacologically highly relevant class of complex saccharides, possessing a linear sequence and strongly acidic character. Their repetitive linear core makes them seem structurally simple at first glance, yet differences in sulfation and epimerization lead to an enormous structural diversity with only a few GAGs having been successfully characterized to date. Recent infrared action spectroscopic experiments on sulfated mono- and disaccharide ions show great promise. Here, we assess the potential of two types of gas-phase action spectroscopy approaches in the range from 1000 to 1800 cm for the structural analysis of complex GAG oligosaccharides. Synthetic tetra- and pentasaccharides were chosen as model compounds for this benchmark study. Utilizing infrared multiple photon dissociation action spectroscopy at room temperature, diagnostic bands are largely unresolved. In contrast, cryogenic infrared action spectroscopy of ions trapped in helium nanodroplets yields resolved infrared spectra with diagnostic features for monosaccharide composition and sulfation pattern. The analysis of GAGs could therefore significantly benefit from expanding the conventional MS-based toolkit with gas-phase cryogenic IR spectroscopy. Graphical abstract.
Topics: Animals; Cold Temperature; Glycosaminoglycans; Helium; Humans; Ions; Isomerism; Oligosaccharides; Spectrophotometry, Infrared; Sulfates
PubMed: 31853603
DOI: 10.1007/s00216-019-02327-7