-
Pediatric Clinics of North America Feb 1967
Review
Topics: Carbohydrate Metabolism, Inborn Errors; Disaccharides; Lactose Intolerance
PubMed: 5333958
DOI: 10.1016/s0031-3955(16)31945-9 -
Pharmacological Research Sep 2022Induction of autophagy is a prospective approach to the treatment of neurodegeneration. In the recent decade, trehalose attracted special attention. It is an autophagy... (Review)
Review
Induction of autophagy is a prospective approach to the treatment of neurodegeneration. In the recent decade, trehalose attracted special attention. It is an autophagy inducer with negligible adverse effects and is approved for use in humans according to FDA requirements. Trehalose has a therapeutic effect in various experimental models of diseases. This glucose disaccharide with a flexible α-1-1'-glycosidic bond has unique properties: induction of mTOR-independent autophagy (with kinase AMPK as the main target) and a chaperone-like effect on proteins imparting them natural spatial structure. Thus, it can reduce the accumulation of neurotoxic aberrant/misfolded proteins. Trehalose has an anti-inflammatory effect and inhibits detrimental oxidative stress partially owing to the enhancement of endogenous antioxidant defense represented by the Nrf2 protein. The disaccharide activates lysosome and autophagosome biogenesis pathways through the protein factors TFEB and FOXO1. Here we review various mechanisms of the neuroprotective action of trehalose and touch on the possibility of pleiotropic effects. Current knowledge about specific features of trehalose pharmacodynamics is discussed. The neuroprotective effects of trehalose in animal models of major neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases are examined too. Attention is given to translational transition to clinical trials of this drug, especially oral and parenteral routes of administration. Besides, the possibility of enhancing the therapeutic benefit via a combination of mTOR-dependent and mTOR-independent autophagy inducers is analyzed. In general, trehalose appears to be a promising multitarget tool for the inhibition of experimental neurodegeneration and requires thorough investigation of its clinical capabilities.
Topics: Animals; Autophagy; Disaccharides; Humans; Neurodegenerative Diseases; TOR Serine-Threonine Kinases; Therapies, Investigational; Trehalose
PubMed: 35907433
DOI: 10.1016/j.phrs.2022.106373 -
Angewandte Chemie (International Ed. in... Dec 2019The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of... (Review)
Review
The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Herein, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides rather than monosaccharides as minimal precursors greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the "sulfation code" and understanding the roles of specific GAG structures in physiology and disease.
Topics: Disaccharides; Heparitin Sulfate; Humans; Polysaccharides
PubMed: 31553820
DOI: 10.1002/anie.201908805 -
Biomacromolecules Mar 2021Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal...
Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal kingdom. However, saccharide-branched GAGs are rarely found, except the fucose-branched one from sea cucumbers. There was conjecture about the presence of disaccharide-branched GAG since 30 years ago, though not yet confirmed. Here, we report a GAG containing galactose-fucose branches from . This unique branch was confirmed as d-Gal-α1,2-l-Fuc by structural elucidation of oligosaccharides prepared from GAG. Bioassays indicated that oligomers with a larger degree of polymerization exhibited a potent anticoagulation by targeting the intrinsic tenase. Heptasaccharide was proven as the minimum fragment retaining the anticoagulant potential and showed 92.6% inhibition of venous thrombosis in vivo at sc. of 8 mg/kg with no obvious bleeding risks. These results not only solve a long-standing question about the presence of disaccharide-branched GAG in Holothuroidea, but open up new opportunities to develop safer anticoagulants.
Topics: Animals; Anticoagulants; Blood Coagulation; Disaccharides; Glycosaminoglycans; Sea Cucumbers
PubMed: 33616386
DOI: 10.1021/acs.biomac.0c01739 -
Methods in Molecular Biology (Clifton,... 2022Glycosaminoglycan (GAG) fine structures from the same animal cells and tissues are controlled not only by the biosynthetic and metabolic enzymes but also by other...
Glycosaminoglycan (GAG) fine structures from the same animal cells and tissues are controlled not only by the biosynthetic and metabolic enzymes but also by other environmental factors, such as chemicals, growth factors, nutritional factors, and isolation procedures. To facilitate direct quantitative comparison of disaccharide compositions from different GAG preparations, several stable isotope labeling strategies have been developed. In this report, 1-phenyl-3-methyl-5-pyrazolone (PMP) and deuterated d5-PMP are used for differential disaccharide labeling and profiling of chondroitin sulfate GAG by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS).
Topics: Animals; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Disaccharides; Glycosaminoglycans; Mass Spectrometry; Polysaccharides
PubMed: 34626374
DOI: 10.1007/978-1-0716-1398-6_10 -
Biochemistry. Biokhimiia Oct 2002The main structural features of an important group of natural compounds, disaccharide nucleosides, are reviewed. The synthesis and properties of modified... (Review)
Review
The main structural features of an important group of natural compounds, disaccharide nucleosides, are reviewed. The synthesis and properties of modified oligonucleotides on their basis as well as the methods of introduction of reactive aldehyde groups are described. The last part is devoted to the application of these compounds for studies of enzymes of nucleic acid metabolism.
Topics: Aldehydes; Base Sequence; Disaccharides; Enzymes; Nucleic Acids; Nucleosides; Oligonucleotides
PubMed: 12460111
DOI: 10.1023/a:1020963207320 -
Archives of Disease in Childhood Dec 1963
Topics: Carbohydrate Metabolism; Chromatography; Disaccharides; Galactose; Humans; Infant; Infant Nutrition Disorders; Lactose; Renal Aminoacidurias; Sucrose; Urine
PubMed: 14085888
DOI: 10.1136/adc.38.202.574 -
The Journal of Organic Chemistry Jan 2023The synthesis of a disaccharide macrocycle through 2,3-dideoxy glucopyranosyl monosaccharide is reported. 2,3-Dideoxy--hexopyranosyl thioglycoside possessing a free...
The synthesis of a disaccharide macrocycle through 2,3-dideoxy glucopyranosyl monosaccharide is reported. 2,3-Dideoxy--hexopyranosyl thioglycoside possessing a free hydroxy functionality at the C-4 carbon is prepared, and cycloglycosylation is conducted. In the event, the cycloglycosylation occurs with a ring contraction of the monosaccharide moiety and affords the cyclic furanoside disaccharide. Solution-phase and single-crystal X-ray diffraction structural characterizations permit the features of the macrocycle to be uncovered. The solubilization and encapsulation properties of the macrocycle are studied in aqueous solutions with 1-aminoadamantane.
Topics: Glycosides; Carbohydrate Sequence; Disaccharides; Crystallography, X-Ray; Monosaccharides
PubMed: 36484560
DOI: 10.1021/acs.joc.2c01936 -
The New Zealand Medical Journal Feb 1966
Review
Topics: Carbohydrate Metabolism, Inborn Errors; Disaccharides; Humans; Infant; Infant, Newborn
PubMed: 5325967
DOI: No ID Found -
Talanta Nov 2022Glycans are the most abundant organic polymers in nature. They are essential to living organisms and regulate a wide range of biological functions. However, mass...
Glycans are the most abundant organic polymers in nature. They are essential to living organisms and regulate a wide range of biological functions. However, mass spectrometry-based identification of glycan isomers remains challenging due to the complexity of their structures including their complex compositions, linkages, and anomeric configurations. In this study, two novel complex ions, the mononuclear copper-bound dimeric ions [(Cu)(A)(L-His)-H] and the mononuclear copper-bound quaternary ions [(Cu)(A)(L-Ser)-H] (where A denotes a disaccharide, and L-Ser/His denotes l-serine/histidine), were designed for the collision-induced dissociation-based identification and relative quantification of 14 disaccharide isomers. When the unique fragmentation patterns of the above two types of complex ions were mapped into a three-dimensional vector, all the isomers were completely distinguished. Of note, the established method is able to identify mixtures of linkage isomers only using tandem mass spectrometry based on linkage-specific fragment ions of histidine-based complex ions. Finally, the method was successfully applied to the identification and relative quantification of two disaccharide isomers (lactose and sucrose) in dairy beverages. In conclusion, the established method is sensitive to subtle structural differences in disaccharide isomers and has the potential to be used for the differentiation of various glycans.
Topics: Copper; Disaccharides; Histidine; Ions; Isomerism; Polysaccharides; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 35717753
DOI: 10.1016/j.talanta.2022.123674