-
Se Pu = Chinese Journal of... Feb 2023Heparin (Hp) is the most widely used anticoagulant drug in the clinics, with an annual global output of over 10 billion dollars. Hp, a member of the... (Review)
Review
Heparin (Hp) is the most widely used anticoagulant drug in the clinics, with an annual global output of over 10 billion dollars. Hp, a member of the glycosaminoglycans (GAGs), is prepared from porcine intestinal mucosa via extraction, separation, and purification. Hp is a linear polysaccharide with repeating disaccharide units. Low-molecular-weight heparins (LMWHs) are depolymerized from Hp via chemical or enzymatic degradation. Compared with Hp, LMWHs exhibit less bleeding side effect, milder immunogenicity, and higher bioavailability when injected subcutaneously. In general, Hps, including LMWHs, are high complex drugs with large molecular weights (MWs), inhomogeneous MW distributions, and structural heterogeneity, including different degrees and locations of sulfonation, and unique residues generated from different production processes. Thus, developing efficient analytical methods to elucidate the structures of Hps and characterize or quantitate their properties is extremely challenging. Unfortunately, this problem limits their quality control, production optimization, clinical safety monitoring, and new applications. Research has constantly sought to elucidate the complicated structures of Hp drugs. Among the structural analysis and quality control methods of Hp currently available, chromatographic methods are the most widely studied and used. However, no literature thoroughly summarizes the specific applications of chromatographic methods in the structural analysis, manufacturing process, and quality control of Hp drugs. This paper systematically organizes and describes recent research progresses of the chromatographic methods used to analyze Hp drugs, including the identification and composition of monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The applications, innovations, and limitations of these chromatographic methods are also summarized in this review. The insights obtained in this study will help production and quality control personnel, as well as drug researchers, obtain a deeper understanding of the complex structures of Hp drugs. This paper also provides a comprehensive reference for the structural analysis and quality control of Hps, proposes ideas for the development of new quality control methods, and lays a strong foundation for the in-depth structural elucidation of Hp drugs.
Topics: Animals; Swine; Heparin; Heparin, Low-Molecular-Weight; Anticoagulants; Chromatography; Heparin Lyase; Disaccharides
PubMed: 36725707
DOI: 10.3724/SP.J.1123.2022.07020 -
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 -
Current Opinion in Clinical Nutrition... Jul 2019Trehalose is a disaccharide with manifold industrial, commercial and biomedical uses. In the decade following its initial definition as an autophagy-inducing agent,... (Review)
Review
PURPOSE OF REVIEW
Trehalose is a disaccharide with manifold industrial, commercial and biomedical uses. In the decade following its initial definition as an autophagy-inducing agent, significant advances have been realized in regard to the applicable clinical and preclinical contexts in which trehalose can be deployed. Moreover, the mechanisms by which trehalose exerts its metabolic effects are only beginning to gain clarity. In this review, we will highlight the most recent advances regarding the effectiveness and mechanisms of trehalose actions in metabolic disease, and discuss barriers and opportunities for this class of compounds to advance as a clinical therapeutic.
RECENT FINDINGS
Trehalose reduced cardiometabolic disease burden in diet-induced and genetic models of atherosclerosis, dyslipidemia, hepatic steatosis and insulin tolerance and glucose tolerance. The mechanism by which these effects occurred were pleiotropic, and involved activation of fasting-like processes, including autophagic flux and transcription factor EB. These mechanisms depend heavily on route of administration and disease-specific context. Host and microbial trehalase activity is likely to influence trehalose efficacy in a tissue-dependent manner.
SUMMARY
Trehalose and its analogues are promising cardiometabolic therapeutic agents with pleiotropic effects across tissue types. It is likely that we are only beginning to uncover the broad efficacy and complex mechanisms by which these compounds modulate host metabolism.
Topics: Animals; Autophagy; Blood Glucose; Disease Models, Animal; Humans; Metabolic Diseases; Mice; Trehalose
PubMed: 31033580
DOI: 10.1097/MCO.0000000000000568 -
The New England Journal of Medicine Feb 2021
Topics: Anaphylaxis; Antibodies; Diagnosis, Differential; Diarrhea; Disaccharides; Food Hypersensitivity; Humans; Immunoglobulin E; Middle Aged; Red Meat; Syncope; Tick-Borne Diseases; Urticaria
PubMed: 33534979
DOI: 10.1056/NEJMcps2017588 -
Current Genetics Apr 2020Desiccation is a common stress that bacteria face in the natural environment, and thus, they have developed a variety of protective mechanisms to mitigate the damage... (Review)
Review
Desiccation is a common stress that bacteria face in the natural environment, and thus, they have developed a variety of protective mechanisms to mitigate the damage caused by water loss. The formation of biofilms and the accumulation of trehalose and sporulation are well-known strategies used by bacteria to survive desiccation. Other mechanisms, including intrinsically disordered proteins and the anti-glycation defence, have been mainly studied in eukaryotic cells, and their role in bacteria remains unclear. We have recently shown that the impairment of trehalose synthesis results in higher glucose availability, leading to the accumulation of acetyl phosphate and enhanced protein acetylation, which in turn stimulates protein aggregation. In the absence of trehalose synthesis, excess glucose may stimulate non-enzymatic glycosylation and the formation of advanced glycation end products (AGEs) bound to proteins. Therefore, we propose that trehalose may prevent protein damage, not only as a chemical chaperone but also as a metabolite that indirectly counteracts detrimental protein acetylation and glycation.
Topics: Bacteria; Bacterial Physiological Phenomena; Desiccation; Glucose; Glycation End Products, Advanced; Intrinsically Disordered Proteins; Protein Aggregates; Trehalose
PubMed: 31559453
DOI: 10.1007/s00294-019-01036-z -
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 -
Nature Aug 2022The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry....
The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly significant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly reactive nucleophilic sites in stereochemically complex contexts. Chemists have generally relied on multi-step protecting-group strategies to achieve site control in glycosylations, but practical inefficiencies arise directly from the application of such approaches. Here we describe a strategy for small-molecule-catalyst-controlled, highly stereo- and site-selective glycosylations of unprotected or minimally protected mono- and disaccharides using precisely designed bis-thiourea small-molecule catalysts. Stereo- and site-selective galactosylations and mannosylations of a wide assortment of polyfunctional nucleophiles is thereby achieved. Kinetic and computational studies provide evidence that site-selectivity arises from stabilizing C-H/π interactions between the catalyst and the nucleophile, analogous to those documented in sugar-binding proteins. This work demonstrates that highly selective glycosylation reactions can be achieved through control of stabilizing non-covalent interactions, a potentially general strategy for selective functionalization of carbohydrates.
Topics: Catalysis; Chemistry Techniques, Synthetic; Disaccharides; Glycosylation; Kinetics; Monosaccharides; Stereoisomerism; Sugars
PubMed: 35709829
DOI: 10.1038/s41586-022-04958-w -
Food Research International (Ottawa,... May 2022Consumers are concerned with the amount of sucrose added to foods and its effects on human health. One way to reduce this concern is through the consumption of sucrose... (Review)
Review
Consumers are concerned with the amount of sucrose added to foods and its effects on human health. One way to reduce this concern is through the consumption of sucrose substitutes, such as isomaltulose. Isomaltulose is an alternative sugar that should be regarded by the food industry as much healthier than sucrose, due to its beneficial properties; these include, low glycemic index and slow hydrolysis, prebiotic potential, and low cariogenic potential. In this work, a bibliometric analysis associated with a review of literature was conducted as a rigorous method for exploring and analyzing large volumes of scientific data, to understand the global scenario and identify the trends regarding isomaltulose. Important facts from its history and origin were discussed, as well the main research and countries that have contributed to its growing interest in the food industry. Over the years, from the discovery of new beneficial properties, more studies have been conducted, demonstrating that the interest in isomaltulose has been increasing. Finally, we concluded that isomaltulose is a promising sucrose substitute that could change the scenario of the sugar-rich foods market; and its use for the development of new products is highly encouraged.
Topics: Bibliometrics; Humans; Hydrolysis; Isomaltose; Sucrose
PubMed: 35400439
DOI: 10.1016/j.foodres.2022.111061 -
Molecules (Basel, Switzerland) May 2024Trehalose is a naturally occurring, non-reducing saccharide widely distributed in nature. Over the years, research on trehalose has revealed that this initially thought... (Review)
Review
Trehalose is a naturally occurring, non-reducing saccharide widely distributed in nature. Over the years, research on trehalose has revealed that this initially thought simple storage molecule is a multifunctional and multitasking compound protecting cells against various stress factors. This review presents data on the role of trehalose in maintaining cellular homeostasis under stress conditions and in the virulence of bacteria and fungi. Numerous studies have demonstrated that trehalose acts in the cell as an osmoprotectant, chemical chaperone, free radical scavenger, carbon source, virulence factor, and metabolic regulator. The increasingly researched medical and therapeutic applications of trehalose are also discussed.
Topics: Trehalose; Humans; Animals; Fungi; Bacteria; Homeostasis; Stress, Physiological
PubMed: 38731579
DOI: 10.3390/molecules29092088 -
Yakugaku Zasshi : Journal of the... 2021Two novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus... (Review)
Review
Two novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus galloprovincialis. It was consisted of 149 amino acid residues and there was no similarity with any other proteins when it was discovered. We advocate for this "Mytilectin" as a new protein family because of their novelty of its primary structure and homologues were also found in other mussels. Glycan array analysis revealed that MytiLec-1 specifically bound to the Gb3 and Gb4 glycan which contained the α-galactoside. MytiLec-1 caused the apoptosis against the Burkitt's lymphoma cells through the interaction of Gb3 express in their cell surface. On the other hand, SeviL obtained from gill and mantle of Mytilisepta virgata showed the specific binding against GM1b, asialo GM1 and SSEA-4 which are known as glycosphingolipid glycan including the β-galactoside. In addition, SeviL was identified as R type lectin by confirmation of QXW motif within its primary structure. Messenger RNA of SeviL like R type lectins was also found among the musssels including Mytilus galloprovincialis. SeviL also showed the apoptosis against asialo GM1 expressing cells. To apply the anticancer lectin as a novel molecular target drug, primary structure of MytiLec-1 was analyzed to enhance the stabilization of confirmation by computational design technique. It was succeeded to produce a monomeric artificial β-trefoil lectin, Mitsuba-1 without losing the Gb3 binding ability. Comparison of biological function between Mitsuba-1 and MytiLec-1 is also described in this study.
Topics: Animals; Antineoplastic Agents; Burkitt Lymphoma; Disaccharides; Drug Design; Galectins; Lectins; Molecular Conformation; Molecular Targeted Therapy; Mytilidae; Polysaccharides; Tandem Repeat Sequences; Trisaccharides
PubMed: 33790114
DOI: 10.1248/yakushi.20-00215