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Carbohydrate Research Nov 2023Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have... (Review)
Review
Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have considerable therapeutic potential, and are used as drugs in the treatment of diabetes and infectious diseases. The development of this branch of carbohydrate chemistry would not be possible without the development of novel methods for its synthesis and the analysis of their biochemical properties. In this Review Article, we summarize our findings on the biological properties of a collection of thio sugars and their derivatives synthesized by the Witczak and Bielski team using their original methods based on the Michael addition of sugar thiols to levoglucosenone.
Topics: Disaccharides; Thiosugars
PubMed: 37708795
DOI: 10.1016/j.carres.2023.108934 -
Srpski Arhiv Za Celokupno Lekarstvo 2010Disaccharide intolerance presents a pathogenic heterogeneous and most complex clinical entity. It usually occurs due to primary or secondary deficit of disaccharide...
Disaccharide intolerance presents a pathogenic heterogeneous and most complex clinical entity. It usually occurs due to primary or secondary deficit of disaccharide activity, and rarely because of disorders of absorption or monomer metabolism. Symptomatology of disaccharide maldigestion and/or malabsorption depends on the severity of the basic disorder, the level of its overload and the patient's age. In the youngest children, due to a rapid gastrointestinal transit and a low compensatory capacity of the colon, osmotic-fermentative diarrhoea forms the basis of clinical features. Diarrhoeal disorder can be occasionally so intensive that it disturbs not only water and electrolytic balance, but also the nutritive status of the child. In older children and adults, as well as in milder forms of the disorder, the symptomatology, most often without diarrhoea, is dominated by abdominal colic, loud peristaltic sounds, meteorism and increased flatulence. Metabolic disorders followed by conversion disorders of galactose and fructose into glucose are characterized by a hypoglycaemic crisis, as well as by various multisystemic damages due to the deposit of toxic metabolic products. The diagnosis of gastrointestinal forms of disaccharide intolerance is based on the pathologic clinical and laboratory response during the overload test, while that of the metabolic form is based on the confirmed presence of specific enzyme and/or genetic defect. Treatment of disaccharide intolerance is based on the elimination diet. Besides, in the secondary forms of the disorder, it is also necessary to apply the treatment of the basic disease.
Topics: Adult; Child; Diarrhea; Dietary Carbohydrates; Disaccharides; Humans; Malabsorption Syndromes
PubMed: 21365893
DOI: 10.2298/sarh1012777r -
Acta Biomaterialia Sep 2023Decellularized lung scaffolds and hydrogels are increasingly being utilized in ex vivo lung bioengineering. However, the lung is a regionally heterogenous organ with...
Decellularized lung scaffolds and hydrogels are increasingly being utilized in ex vivo lung bioengineering. However, the lung is a regionally heterogenous organ with proximal and distal airway and vascular compartments of different structures and functions that may be altered as part of disease pathogenesis. We previously described decellularized normal whole human lung extracellular matrix (ECM) glycosaminoglycan (GAG) composition and functional ability to bind matrix-associated growth factors. We now determine differential GAG composition and function in airway, vascular, and alveolar-enriched regions of decellularized lungs obtained from normal, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) patients. Significant differences were observed in heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA) content and CS/HS compositions between both different lung regions and between normal and diseased lungs. Surface plasmon resonance demonstrated that HS and CS from decellularized normal and COPD lungs similarly bound fibroblast growth factor 2, but that binding was decreased in decellularized IPF lungs. Binding of transforming growth factor β to CS was similar in all three groups but binding to HS was decreased in IPF compared to normal and COPD lungs. In addition, cytokines dissociate faster from the IPF GAGs than their counterparts. The differences in cytokine binding features of IPF GAGs may result from different disaccharide compositions. The purified HS from IPF lung is less sulfated than that from other lungs, and the CS from IPF contains more 6-O-sulfated disaccharide. These observations provide further information for understanding functional roles of ECM GAGs in lung function and disease. STATEMENT OF SIGNIFICANCE: Lung transplantation remains limited due to donor organ availability and need for life-long immunosuppressive medication. One solution, the ex vivo bioengineering of lungs via de- and recellularization has not yet led to a fully functional organ. Notably, the role of glycosaminoglycans (GAGs) remaining in decellularized lung scaffolds is poorly understood despite their important effects on cell behaviors. We have previously investigated residual GAG content of native and decellularized lungs and their respective functionality, and role during scaffold recellularization. We now present a detailed characterization of GAG and GAG chain content and function in different anatomical regions of normal diseased human lungs. These are novel and important observations that further expand knowledge about functional GAG roles in lung biology and disease.
Topics: Humans; Glycosaminoglycans; Lung; Chondroitin Sulfates; Pulmonary Disease, Chronic Obstructive; Extracellular Matrix; Disaccharides
PubMed: 37433361
DOI: 10.1016/j.actbio.2023.06.043 -
Journal of Animal Science Feb 2022A completely randomized design employing a 2 × 2 factorial experiment was designed in this study to evaluate the effects of in ovo injection of disaccharide (DS)...
A completely randomized design employing a 2 × 2 factorial experiment was designed in this study to evaluate the effects of in ovo injection of disaccharide (DS) and/or methionine (Met) on hatchability, growth performance, blood hematology, and serum antioxidant parameters in geese. A total of 600 fertilized geese's eggs containing live embryo were randomly assigned into 4 groups with 6 replicates and 25 eggs per replicate. Factors in four groups comprised noninjection, DS injection (25 g/L maltose + 25 g/L sucrose + 7.5 g/L NaCl), Met injection (5 g/L Met + 7.5 g/L NaCl), or DS plus Met injection (25 g/L maltose + 25 g/L sucrose + 5 g/L Met + 7.5 g/L NaCl), respectively. We found that the administration of DS in embryo increased hatching time, yolk sac-free carcass weight, yolk sac-free carcass indexes and decreased assisted hatching ratio, yolk sac weight, yolk sac indexes, but did not affect hatchability and mortality. Moreover, higher body weight and serum glucose concentrations in DS injection group compared with noninjection group were observed on day of hatching. The body weight and average daily gain (ADG) of geese in DS injection group were higher than noninjection group after incubation. In ovo injection of Met increased hatching time and yolk sac-free carcass indexes, but decreased yolk sac indexes. In addition, the strategy of in ovo feeding of Met led to higher body weight, ADG, serum uric acid, glutathione (GSH), and glutathione peroxidase concentrations, as well as lower GSSG/GSH ratio, serum glutathione disulfide (GSSG), and malondialdehyde (MDA) concentrations than the noninjection group on day of hatching. The post-hatching body weight, ADG, serum total protein, albumin, and uric acid concentrations increased, whereas post-hatching serum GSSG and MDA concentrations and GSSG/GSH ratio decreased when injected with Met. In addition, synergistic effects of in ovo injection of DS plus Met on hatching time as well as post-hatching body weight and ADG were observed. Therefore, in ovo injection of DS plus Met was demonstrated to be a way to improve the development of geese during early incubation stages.
Topics: Animals; Antioxidants; Chickens; Disaccharides; Geese; Hematology; Methionine; Ovum; Uric Acid
PubMed: 35094079
DOI: 10.1093/jas/skac014 -
Biomedicine & Pharmacotherapy =... Jun 2022Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength,... (Review)
Review
Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength, purity, and cheap cost-effectiveness. Citrus fruits contain significant amounts of flavanones, which falls to the category of polyphenols. Flavanones occupy a major fraction of the total polyphenols present in the plasma when orange juice is taken highly or in moderate states. Narirutin is a disaccharide derivative available in citrus fruits, primarily dihydroxy flavanone. From a pharmacological viewpoint, narirutin is a bioactive phytochemical with therapeutic efficacy. Many experimental researches were published on the use of narirutin. Anticancer activity, neuroprotection, stress relief, hepatoprotection, anti-allergic activity, antidiabetic activity, anti-adipogenic activity, anti-obesity action, and immunomodulation are a couple of the primary pharmacological properties. Narirutin also has antioxidant, and anti-inflammatory activities. The ultimate goal of this review is to provide the current scenario of pharmacological research with narirutin; to make a better understanding for therapeutic potential of narirutin, as well as its biosynthesis strategies and side effects. Extensive literature searches and studies were undertaken to determine the pharmacological properties of narirutin.
Topics: Citrus; Disaccharides; Flavanones; Flavonoids; Polyphenols; Prospective Studies
PubMed: 35413599
DOI: 10.1016/j.biopha.2022.112932 -
Organic Letters Jun 2021Stereoselective reactions at the anomeric carbon constitute the cornerstone of preparative carbohydrate chemistry. Here, we report stereoselective C-arylation and...
Stereoselective reactions at the anomeric carbon constitute the cornerstone of preparative carbohydrate chemistry. Here, we report stereoselective C-arylation and etherification reactions of anomeric trifluoroborates derived from BMIDA esters. These reactions are characterized by high anomeric selectivities for 2-deoxysugars and broad substrate scope (24 examples), including disaccharides and trifluoroborates with free hydroxyl groups. Taken together, this new class of carbohydrate reagents adds the palette of anomeric nucleophile reagents suitable for efficient installation of C-C bonds.
Topics: Borates; Carbon; Disaccharides; Esters; Molecular Structure; Stereoisomerism
PubMed: 34029464
DOI: 10.1021/acs.orglett.1c01035 -
Biophysical Journal May 2011Galectin-1, a member of the conserved family of carbohydrate-binding proteins with affinity for β-galactosides, is a key modulator of diverse cell functions such as...
Galectin-1, a member of the conserved family of carbohydrate-binding proteins with affinity for β-galactosides, is a key modulator of diverse cell functions such as immune response and regulation. The binding affinity and specificity of galectin-1 for eight different β-galactosyl terminal disaccharides was studied using molecular-dynamics simulations in which the ligand was pulled away from the binding site using a mechanical force. We present what we believe to be a novel procedure, based on combinations of multistep trajectories, that was used to estimate the binding free energy (ΔG) of each disaccharide. The computed binding free energy differences show excellent correlation with experimental values determined previously. The small differences in affinity among the disaccharides are the result of an exquisite balance between the strengths of the galectin-sugar H-bonds and the H-bonds the protein and the disaccharides make with the solvent. Analysis of the free energies along the reaction coordinate shows that disaccharide unbinding/binding presents no energetic barrier and, therefore, is diffusion-limited. In addition, the calculations revealed that as the ligand is undocked from the binding site, breaking of protein-disaccharide H-bonds takes place in stages with intermediate states in which the interactions are bridged by water molecules.
Topics: Animals; Cattle; Crystallography, X-Ray; Disaccharides; Galectin 1; Glucosamine; Hydrogen Bonding; Molecular Dynamics Simulation; Pliability; Protein Binding; Protein Conformation; Solvents; Thermodynamics; Water
PubMed: 21539798
DOI: 10.1016/j.bpj.2011.03.032 -
Journal of Medicinal Chemistry Dec 2023In recent years, trehalose, a natural disaccharide, has attracted growing attention because of the discovery of its potential to induce autophagy. Trehalose has also... (Review)
Review
In recent years, trehalose, a natural disaccharide, has attracted growing attention because of the discovery of its potential to induce autophagy. Trehalose has also been demonstrated to preserve the protein's structural integrity and to limit the aggregation of pathologically misfolded proteins. Both of these properties have made trehalose a promising therapeutic candidate to target autophagy-related disorders and protein aggregation diseases. Unfortunately, trehalose has poor bioavailability due to its hydrophilic nature and susceptibility to enzymatic degradation. Recently, trehalose-bearing carriers, in which trehalose is incorporated either by chemical conjugation or physical entrapment, have emerged as an alternative option to free trehalose to improve its efficacy, particularly for the treatment of neurodegenerative diseases, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and cancers. In the current Perspective, we discuss all existing literature in this emerging field and try to identify key challenges for researchers intending to develop trehalose-bearing carriers to stimulate autophagy or inhibit protein aggregation.
Topics: Humans; Trehalose; Protein Aggregates; Disaccharides; Autophagy; Neurodegenerative Diseases
PubMed: 38031413
DOI: 10.1021/acs.jmedchem.3c01442 -
Poultry Science Oct 2022This study was conducted to investigate the effects of in ovo injection of methionine (Met) and/or disaccharide (DS) on post-hatching pectoral muscle and small intestine...
Effects of methionine and/or disaccharide injected in the amnion of geese on post-hatching pectoral muscle and small intestine development, glycogen reserves, jejunum morphology, and digestive enzymes activities.
This study was conducted to investigate the effects of in ovo injection of methionine (Met) and/or disaccharide (DS) on post-hatching pectoral muscle and small intestine development, glycogen reserves, jejunum morphology, and jejunum digestive enzymes activities. A total of 600 fertilized eggs containing live embryo from geese were randomly assigned into 4 groups with 6 replicates and 25 eggs per replicate in a completely randomized design employing a 2 × 2 factorial experiment. Factors in 4 groups included noninjection, Met injection (5 g/L Met + 7.5 g/L NaCl), DS injection (25 g/L maltose + 25 g/L sucrose + 7.5 g/L NaCl), or DS plus Met injection (25 g/L maltose + 25 g/L sucrose + 5 g/L Met + 7.5g/L NaCl), respectively. In ovo nutritional injections were performed at day 23 of incubation, and the experiment until d 21 post-hatching. We found that in ovo feeding of Met increased relative weight of pectoral muscle and small intestine, jejunum alkaline phosphatase activities, and jejunum villus height and surface area. DS injection improved the relative weight of pectoral muscle, pectoral and liver glycogen contents, jejunum villus height, width, and surface area, and jejunum sucrase, Na/KATPase, and alkaline phosphatase activities. In addition, Met plus DS injection synergistically improved jejunum villus height and surface area. Therefore, Met plus DS injection is a suitable strategy for improving intestinal parameters in gosling during post-hatching periods.
Topics: Adenosine Triphosphatases; Alkaline Phosphatase; Amnion; Animals; Chickens; Disaccharides; Geese; Glycogen; Intestine, Small; Jejunum; Liver Glycogen; Maltose; Methionine; Ovum; Pectoralis Muscles; Racemethionine; Sodium Chloride; Sucrase; Sucrose
PubMed: 35986947
DOI: 10.1016/j.psj.2022.101867 -
Bioconjugate Chemistry Jun 2022Antibody-drug conjugates (ADCs) hold great promise for targeted cancer cell killing. Site-specific antibody-drug conjugation is highly desirable for synthesizing...
Antibody-drug conjugates (ADCs) hold great promise for targeted cancer cell killing. Site-specific antibody-drug conjugation is highly desirable for synthesizing homogeneous ADCs with optimal safety profiles and high efficacy. We have recently reported that azide-functionalized disaccharide oxazolines of the Man1,4GlcNAc core were an efficient substrate of wild-type endoglycosidase Endo-S2 for Fc glycan remodeling and conjugation. In this paper, we report the synthesis and evaluation of new disaccharide oxazolines as enzyme substrates for examining the scope of the site-specific conjugation. Thus, azide-functionalized disaccharide oxazolines derived from Man1,4GlcNAc, Glc1,4GlcNAc, and Gal1,4GlcNAc (LacNAc) were synthesized. Enzymatic evaluation revealed that wild-type Endo-S2 demonstrated highly relaxed substrate specificity and could accommodate all the three types of disaccharide derivatives for transglycosylation to provide site-specific azide-tagged antibodies, which were readily clicked with a payload to generate homogeneous ADCs. Moreover, we also found that Endo-S2 was able to accommodate drug-preloaded minimal disaccharide oxazolines as donor substrates for efficient glycan transfer, enabling a single-step and site-specific antibody-drug conjugation without the need of an antibody click reaction. The ability of Endo-S2 to accommodate simpler and more easily synthesized disaccharide oxazoline derivatives for Fc glycan remodeling further expanded the scope of this bioconjugation method for constructing homogeneous antibody-drug conjugates in a single-step manner. Finally, cell-based assays indicated that the synthetic homogeneous ADCs demonstrated potent targeted cancer cell killing.
Topics: Antibodies; Azides; Disaccharides; Immunoconjugates; Immunoglobulin Fc Fragments; Polysaccharides
PubMed: 35543724
DOI: 10.1021/acs.bioconjchem.2c00142