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Chembiochem : a European Journal of... Jan 2019A general strategy for the diverse synthesis of ten disaccharide aminoglycosides, including natural 2-trehalosamine (1), 3-trehalosamine (2), 4-trehalosamine (3), and...
A general strategy for the diverse synthesis of ten disaccharide aminoglycosides, including natural 2-trehalosamine (1), 3-trehalosamine (2), 4-trehalosamine (3), and neotrehalosyl 3,3'-diamine (8) and synthetic aminoglycosides 4-7, 9, and 10, has been developed. The aminoglycoside compounds feature different anomeric configurations and numbers of amino groups. The key step for the synthesis was the glycosylation coupling of a stereodirecting donor with a configuration-stable TMS glycoside acceptor. Either the donor or acceptor could be substituted with an azido group. The aminoglycosides prepared in the present study were characterized by 1D and 2D NMR spectroscopy.
Topics: Amino Sugars; Aminoglycosides; Biological Products; Carbohydrate Conformation; Disaccharides
PubMed: 30421539
DOI: 10.1002/cbic.201800656 -
Methods in Enzymology 1978
Review
Topics: Animals; Carbohydrates; Disaccharides; Glycoproteins; Glycosaminoglycans; Glycosphingolipids; Humans; Polysaccharides
PubMed: 351330
DOI: 10.1016/0076-6879(78)50028-1 -
Analytical Chemistry Jan 2013Heparan sulfate (HS) and chondroitin sulfate/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) participate in many important biological processes. Quantitative...
Heparan sulfate (HS) and chondroitin sulfate/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) participate in many important biological processes. Quantitative disaccharide analysis of HS and CS/DS is essential for the characterization of GAGs and enables modeling of the GAG domain structure. Methods involving enzymatic digestion and chemical depolymerization have been developed to determine the type and location of sulfation/acetylation modifications as well as uronic acid epimerization. Enzymatic digestion generates disaccharides with Δ-4,5-unsaturation at the nonreducing end. Chemical depolymerization with nitrous acid retains the uronic acid epimerization. This work shows the use of hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) for quantification of both enzyme-derived and nitrous acid depolymerization products for structural analysis of HS and CS/DS. This method enables biomedical researchers to determine complete disaccharide profiles on GAG samples using a single LC-MS platform.
Topics: Chromatography, Liquid; Disaccharides; Glycosaminoglycans; Hydrophobic and Hydrophilic Interactions; Mass Spectrometry
PubMed: 23234263
DOI: 10.1021/ac3030448 -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024Glycosaminoglycans (GAGs) are linear and acidic polysaccharides. They are ubiquitous molecules, which are involved in a wide range of biological processes. Despite being...
Glycosaminoglycans (GAGs) are linear and acidic polysaccharides. They are ubiquitous molecules, which are involved in a wide range of biological processes. Despite being structurally simple at first glance, with a repeating backbone of alternating hexuronic acid and hexosamine dimers, GAGs display a highly complex structure, which predominantly results from their heterogeneous sulfation patterns. The commonly applied method for compositional analysis of all GAGs is "disaccharide analysis." In this process, GAGs are enzymatically depolymerized into disaccharides, derivatized with a fluorescent label, and then analysed through liquid chromatography. The limiting factor in the high throughput analysis of GAG disaccharides is the time-consuming liquid chromatography. To address this limitation, we here utilized trapped ion mobility-mass spectrometry (TIM-MS) for the separation of isomeric GAG disaccharides, which reduces the measurement time from hours to a few minutes. A full set of disaccharides comprises twelve structures, with eight possessing isomers. Most disaccharides cannot be differentiated by TIM-MS in underivatized form. Therefore, we developed chemical modifications to reduce sample complexity and enhance differentiability. Quantification is performed using stable isotope labelled standards, which are easily available due to the nature of the performed modifications.
Topics: Disaccharides; Glycosaminoglycans; Ion Mobility Spectrometry; Mass Spectrometry; Isomerism; Chromatography, Liquid
PubMed: 38629399
DOI: 10.1002/chem.202400783 -
Angewandte Chemie (International Ed. in... May 2021GlcNAc is the core disaccharide fragment present in N-glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because...
GlcNAc is the core disaccharide fragment present in N-glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because N-glycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methyl-β-glycoside of GlcNAc in water with an unprecedented affinity of 160 μM, exceeding that of more structurally complex receptors reported in the literature. The tweezers-shaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between mono- and disaccharides. Molecular modelling calculations supported by NOE data provided a three-dimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor.
Topics: Biomimetic Materials; Disaccharides; Models, Molecular; Molecular Structure; Water
PubMed: 33666317
DOI: 10.1002/anie.202100560 -
Dermatology (Basel, Switzerland) 1997Altered metabolism of skin glycosaminoglycan has rarely been investigated in localized scleroderma in contrast to systemic sclerosis. (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Altered metabolism of skin glycosaminoglycan has rarely been investigated in localized scleroderma in contrast to systemic sclerosis.
OBJECTIVE
The aim of this investigation is to elucidate the change in skin glycosaminoglycan of localized scleroderma.
METHODS
We analyzed 5 skin samples of localized scleroderma and 10 site-matched control skin samples using high performance liquid chromatography after 1-phenyl-3-methyl-5-pyrasolone labeling.
RESULTS
The involved skin constantly showed an increased amount of delta Di-4S(DS), the main disaccharide unit of dermatan sulfate, a decreased amount of delta Di-HA, the main disaccharide unit of hyaluronic acid, and an elevated ratio of delta Di-4S(DS)/delta Di-HA as compared with the uninvolved skin or the site matched control skin.
CONCLUSION
These results correlate well with those findings in systemic sclerosis, indicating that the alteration in skin GAG may be closely related to the fibrotic process.
Topics: Adult; Aged; Analysis of Variance; Biopsy, Needle; Culture Techniques; Disaccharides; Female; Glycosaminoglycans; Humans; Male; Middle Aged; Scleroderma, Localized; Skin
PubMed: 9252752
DOI: 10.1159/000246127 -
Biochemical Pharmacology Apr 2001The sugar moiety is an essential component of anthracycline antibiotics for their topoisomerase poisoning activity and antitumor efficacy. Since the sugar interacts with... (Review)
Review
The sugar moiety is an essential component of anthracycline antibiotics for their topoisomerase poisoning activity and antitumor efficacy. Since the sugar interacts with the minor groove, modifications in this moiety could enhance the recognition potential of the drug at the target level. Based on this hypothesis, novel anthracyclines, disaccharides lacking the amino group in the first (aglycone-linked) sugar, were designed. The 3'-amino group in the first sugar was replaced by an hydroxyl group, and the second sugar residue was bound to the first sugar via an alpha (1-4) linkage. The cytotoxic and antitumor activities of disaccharide analogs of idarubicin were critically dependent on the optimal (axial) orientation of the second sugar residue. Although configurational requirements of the sugar moiety for optimal drug activity support a critical role of the external (non-intercalating) drug domains in the interaction of anthracyclines with the DNA-topoisomerase (ternary complex), the antitumor efficacy of disaccharide analogs is not fully explained by effects mediated by the nuclear enzyme target. The development of this novel disaccharide series may provide insights for a rational synthesis of anthracycline analogs with improved pharmacological profile.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Disaccharides; Drug Design; Humans; Molecular Conformation; Structure-Activity Relationship
PubMed: 11286984
DOI: 10.1016/s0006-2952(01)00522-6 -
Bioorganic & Medicinal Chemistry Aug 2007Glycosyltransferases (GTs) play a crucial role in mycobacterial cell wall biosynthesis and are necessary for the survival of mycobacteria. Hence, these enzymes are...
Glycosyltransferases (GTs) play a crucial role in mycobacterial cell wall biosynthesis and are necessary for the survival of mycobacteria. Hence, these enzymes are potential new drug targets for the treatment of tuberculosis (TB), especially multiple drug-resistant TB (MDR-TB). Herein, we report the efficient syntheses of Araf(alpha 1-->5)Araf, Galf(beta 1-->5)Galf, and Galf(beta 1-->6)Galf disaccharides possessing a 5-N,N-dimethylaminonaphthalene-1-sulfonamidoethyl (dansyl) unit that were prepared as fluorescent disaccharide acceptors for arabinosyl- and galactosyl-transferases, respectively. Such analogs may offer advantages relative to radiolabeled acceptors or donors for studying the enzymes and for assay development and compound screening. Additionally, analogs possessing a 5-azidonaphthalene-1-sulfonamidoethyl unit were prepared as photoaffinity probes for their potential utility in studying active site labeling of the GTs (arabinosyl and galactosyl) in Mycobacterium tuberculosis (MTB). Beyond their preparation, initial biological testing and kinetic analysis of these disaccharides as acceptors toward glycosyltransferases are also presented.
Topics: Catalysis; Disaccharides; Galactans; Glycosylation; Glycosyltransferases; Magnetic Resonance Spectroscopy; Molecular Structure; Mycobacterium tuberculosis; Oxidation-Reduction; Photochemistry
PubMed: 17544276
DOI: 10.1016/j.bmc.2007.04.012 -
Analytical Methods : Advancing Methods... Jan 2024Chondroitin sulphate (CS) and dermatan sulphate are negatively charged linear heteropolysaccharides. These glycosaminoglycans (GAG) are involved in cellular signalling...
Chondroitin sulphate (CS) and dermatan sulphate are negatively charged linear heteropolysaccharides. These glycosaminoglycans (GAG) are involved in cellular signalling binding to growth factors. CS is expressed in a range of tissue and biological fluids and is highly expressed in the placenta. There is evidence that decorin; a CS proteoglycan is significantly decreased in pre-eclampsia and fetal growth restriction. It is considered that GAG chain composition may influence cellular processes that are altered in pre-eclampsia. The goal of the present study was to develop an LC-MS method with precolumn procainamide labelling for the disaccharide compositional analysis of CS. The method was used to investigate whether the disaccharide composition of placenta-extracted CS is altered in pre-eclampsia. The study revealed differential disaccharide compositions of placental chondroitin sulphate between pre-eclampsia and other pregnancy conditions. This suggests that the method may have diagnostic potential for pregnancy disorders. Furthermore, the findings suggest that CS sulphation might play a significant role in maternal labour.
Topics: Female; Pregnancy; Humans; Chondroitin Sulfates; Procainamide; Pre-Eclampsia; Disaccharides; Placenta; Glycosaminoglycans
PubMed: 38189556
DOI: 10.1039/d3ay01578e -
Tidsskrift For Den Norske Laegeforening... Apr 1963
Topics: Disaccharides; Metabolic Diseases
PubMed: 13979550
DOI: No ID Found