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Journal of the American Chemical Society Oct 2022Stapling short peptides to lock specific conformations and thereby obtain superior pharmacological properties is well established. However, similar concepts have not...
Stapling short peptides to lock specific conformations and thereby obtain superior pharmacological properties is well established. However, similar concepts have not been applied to oligosaccharides. Here, we describe the design, synthesis, and characterization of the first stapled oligosaccharides. Automated assembly of β-(1,6)-glucans equipped with two alkenyl side chains was followed by on-resin Grubbs metathesis for efficient ring closure with a variety of cross-linkers of different sizes. Oligosaccharide stapling increases enzymatic stability and cell penetration, therefore opening new opportunities for the use of glycans in medicinal chemistry.
Topics: Glucans; Molecular Conformation; Oligosaccharides; Peptides; Polysaccharides
PubMed: 36173281
DOI: 10.1021/jacs.2c06882 -
Journal of Animal Science Nov 2019In this study, we evaluated the effects of seven oligosaccharides on the growth rate and stress tolerance of Lactobacillus plantarum ZLP001 in vitro, and the potential...
Effects of oligosaccharides on the growth and stress tolerance of Lactobacillus plantarum ZLP001 in vitro, and the potential synbiotic effects of L. plantarum ZLP001 and fructo-oligosaccharide in post-weaning piglets1.
In this study, we evaluated the effects of seven oligosaccharides on the growth rate and stress tolerance of Lactobacillus plantarum ZLP001 in vitro, and the potential synbiotic effects of the most effective oligosaccharide [fructo-oligosaccharide (FOS)] and L. plantarum ZLP001 on the growth performance, apparent nutrient digestibility, fecal microbiota, and serum immune index in weaning piglets. Most oligosaccharides were utilized as carbohydrate sources by L. plantarum ZLP001, but we observed obvious differences in the bacterial growth depending on oligosaccharide type and concentration. Oligosaccharides and glucose significantly alleviated the decrease in L. plantarum ZLP001 viability in artificial gastric fluid, whereas none of the sugars affected viability in artificial intestinal fluid. FOS and galacto-oligosaccharide significantly improved the viability of L. plantarum ZLP001 under heat stress (65 °C for 15 and 30 min). FOS and soybean oligosaccharide significantly increased the viability of L. plantarum ZLP001 in response to cold stress (4 °C for 30 and 60 days). On the basis of the findings of in vitro experiments, we selected FOS for in vivo studies. Eighty-four weaned piglets were randomly assigned to one of the following groups: control (basal diet, no additives), freeze-dried L. plantarum ZLP001 (4.2 × 109 CFU/g, 2 g/kg diet), FOS (5 g/kg diet), and combination (0.2% L. plantarum ZLP001 + 0.5% FOS). Body weight and feed consumption were recorded for determinations of the average daily gain (ADG), average daily feed intake (ADFI), and feed-to-gain ratio (F/G). On day 28, fresh fecal samples were collected to evaluate the apparent digestibility of nutrients and microbiota, and serum samples were collected to determine the immune status. L. plantarum ZLP001 plus FOS significantly increased ADG and decreased the F/G ratio compared with the no-additive control. The combination treatment also increased the apparent nutrient digestibility of dry matter and crude protein. Compared with the control and single supplementation, the combination treatment had a significant regulatory effect on the intestinal microbiota, as evidenced by increases in Lactobacillus spp. and a decrease in Enterobacteriaceae. In addition, the combination treatment increased the concentrations of serum IFN-γ and immunoglobulin G. In conclusion, FOS can be utilized well by L. plantarum ZLP001 and can be combined with it as a potential synbiotic that shows synergistic effects in weaning piglets.
Topics: Animal Feed; Animals; Diet; Feces; Gastrointestinal Microbiome; Lactobacillus plantarum; Oligosaccharides; Random Allocation; Glycine max; Stress, Physiological; Swine; Synbiotics; Weaning
PubMed: 31410455
DOI: 10.1093/jas/skz254 -
BMB Reports Aug 2012Human milk, which nourishes the early infants, is a source of bioactive components for the infant growth, development and commensal formulation as well. Human milk... (Review)
Review
Human milk, which nourishes the early infants, is a source of bioactive components for the infant growth, development and commensal formulation as well. Human milk oligosaccharide is a group of complex and diverse glycans that is apparently not absorbed in human gastrointestinal tract. Although most mammalian milk contains oligosaccharides, oligosaccharides in human milk exhibit unique features in terms of their types, amounts, sizes, and functionalities. In addition to the prevention of infectious bacteria and the development of early immune system, human milk oligosaccharides are able to facilitate the healthy intestinal microbiota. Bifidobacterial intestinal microbiota appears to be established by the unilateral interaction between milk oligosaccharides, human intestinal activity and commensals. Digestibility, membrane transportation and catabolic activity by bacteria and intestinal epithelial cells, all of which are linked to the structural of human milk oligosaccharides, are crucial in determining intestinal microbiota.
Topics: Bacteria; Carbohydrate Conformation; Glycoside Hydrolases; Humans; Intestinal Mucosa; Intestines; Metagenome; Milk, Human; Oligosaccharides
PubMed: 22917027
DOI: 10.5483/BMBRep.2012.45.8.168 -
Journal of Nutritional Science 2020Apart from its role as a digestive and absorptive organ, the gastrointestinal (GI) tract is a vital immune organ that encompasses roughly 70 % of the total immune cells... (Review)
Review
Apart from its role as a digestive and absorptive organ, the gastrointestinal (GI) tract is a vital immune organ that encompasses roughly 70 % of the total immune cells of the body. As such, the physical, chemical and nutrient composition of the diet influences overall GI function, effectively as an immune organ. With the improvement in feed technology, agro-industrial co-products that are high in fibre have been widely used as a feed ingredient in the diets of pigs and poultry. Arabinoxylan (AX) and mannan are the most abundant hemicellulosic polysaccharides present in cereal grain and co-product ingredients used in the livestock industry. When monogastric animals consume diets containing high amounts of AX and mannans, stimulation of GI immune cells may occur. This involves the activation of several cellular and molecular pathways of the immune system and requires a considerable amount of energy and nutrients to be expended by the animal, which may ultimately influence overall health and growth performance of animals. Therefore, a better understanding of the role of AX and mannan in immune modulation will be helpful in modulating untoward GI immune responses, thereby minimising nutrient and energy expenditure toward this effort. This review will summarise pertinent research on the role of oligosaccharides and polysaccharides containing AX and mannans in immune modulation in order to preserve gut integrity.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Diet; Dietary Fiber; Digestion; Edible Grain; Gastrointestinal Tract; Mannans; Molecular Weight; Oligosaccharides; Polysaccharides; Solubility; Viscosity; Xylans
PubMed: 32595966
DOI: 10.1017/jns.2020.14 -
Acta Cirurgica Brasileira May 2015To address the effects of fructooligosaccharides (FOS) intake on serum cholesterol levels. (Review)
Review
PURPOSE
To address the effects of fructooligosaccharides (FOS) intake on serum cholesterol levels.
METHODS
We performed a search for scientific articles in MEDLINE database from 1987 to 2014, using the following English keywords: fructooligosaccharides; fructooligosaccharides and cholesterol. A total of 493 articles were found. After careful selection and exclusion of duplicate articles 34 references were selected. Revised texts were divided into two topics: "FOS Metabolism" and "FOS effects on plasma cholesterol."
RESULTS
The use of a FOS diet prevented some lipid disorders and lowered fatty acid synthase activity in the liver in insulin-resistant rats. There was also reduction in weight and total cholesterol in beagle dogs on a calorie-restricted diet enriched with short-chain FOS. Another study found that 2g FOS daily consumption increased significantly serum HDL cholesterol levels but did not ensure a significant reduction in levels of total cholesterol and triglycerides.. Patients with mild hypercholesterolemia receiving short-chain FOS 10.6g daily presented no statistically significant reduction in serum cholesterol levels. However, when FOS was offered to patients that changed their lifestyle, the reduction of LDL cholesterol and steatosis was higher.
CONCLUSIONS
Fructooligosaccharides intake may have a beneficial effect on lipid metabolism and regulation of serum cholesterol levels in individuals that change their lifestyle. FOS supplementation use in diets may therefore be a strategy for lowering cholesterol.
Topics: Animals; Cholesterol; Dietary Supplements; Dogs; Dyslipidemias; Humans; Lipid Metabolism; Oligosaccharides; Rats; Reproducibility of Results; Treatment Outcome
PubMed: 26016937
DOI: 10.1590/S0102-865020150050000009 -
Biochemistry. Biokhimiia Jul 2015This review substantiates the need to study the plant oligoglycome. The available information on oligosaccharins - physiologically active fragments of plant cell wall... (Review)
Review
This review substantiates the need to study the plant oligoglycome. The available information on oligosaccharins - physiologically active fragments of plant cell wall polysaccharides - is summarized. The diversity of such compounds in chemical composition, origin, and proved biological activity is highlighted. At the same time, plant oligosaccharides can be considered as outsiders among elicitors of various natures in research intensity of recent decades. This review discusses the reasons for such attitude towards these regulators, which are largely connected with difficulties in isolation and identification. Together with that, approaches are suggested whose potentials can be used to study oligosaccharins. The topics of oligosaccharide metabolism in plants, including the ways of formation, transport, and inactivation are presented, together with data on biological activity and interaction with plant hormones. The current viewpoints on the mode of oligosaccharin action - perception, signal transduction, and possible "targets" - are considered. The potential uses of such compounds in medicine, food industry, agriculture, and biotechnology are discussed.
Topics: Cell Wall; Glucans; Oligosaccharides; Plant Roots; Plants; Polysaccharides; Signal Transduction; Xylans
PubMed: 26542002
DOI: 10.1134/S0006297915070081 -
Carbohydrate Polymers Aug 2022Identification of arabinoxylo-oligosaccharides (AXOS) within complex mixtures is an ongoing analytical challenge. Here, we established a strategy based on hydrophilic...
Identification of arabinoxylo-oligosaccharides (AXOS) within complex mixtures is an ongoing analytical challenge. Here, we established a strategy based on hydrophilic interaction chromatography coupled to collision induced dissociation-mass spectrometry (HILIC-MS) to identify a variety of enzyme-derived AXOS structures. Oligosaccharide reduction with sodium borohydride remarkably improved chromatographic separation of isomers, and improved the recognition of oligosaccharide ends in MS-fragmentation patterns. Localization of arabinosyl substituents was facilitated by decreased intensity of Z ions relative to corresponding Y ions, when fragmentation occurred in the vicinity of substituents. Interestingly, the same B fragment ions (MS) from HILIC-separated AXOS isomers showed distinct MS spectral fingerprints, being diagnostic for the linkage type of arabinosyl substituents. HILIC-MS identification of AXOS was strengthened by using specific and well-characterized arabinofuranosidases. The detailed characterization of AXOS isomers currently achieved can be applied for studying AXOS functionality in complex (biological) matrices. Overall, the present strategy contributes to the comprehensive carbohydrate sequencing.
Topics: Chromatography, Liquid; Hydrophobic and Hydrophilic Interactions; Ions; Oligosaccharides; Tandem Mass Spectrometry
PubMed: 35483836
DOI: 10.1016/j.carbpol.2022.119415 -
Molecules and Cells Dec 2010Quality control of protein folding represents a fundamental cellular activity. Early steps of protein N-glycosylation involving the removal of three glucose and some... (Review)
Review
Quality control of protein folding represents a fundamental cellular activity. Early steps of protein N-glycosylation involving the removal of three glucose and some specific mannose residues in the endoplasmic reticulum have been recognized as being of importance for protein quality control. Specific oligosaccharide structures resulting from the oligosaccharide processing may represent a glycocode promoting productive protein folding, whereas others may represent glyco-codes for routing not correctly folded proteins for dislocation from the endoplasmic reticulum to the cytosol and subsequent degradation. Although quality control of protein folding is essential for the proper functioning of cells, it is also the basis for protein folding disorders since the recognition and elimination of non-native conformers can result either in loss-of-function or pathological-gain-of-function. The machinery for protein folding control represents a prime example of an intricate interactome present in a single organelle, the endoplasmic reticulum. Here, current views of mechanisms for the recognition and retention leading to productive protein folding or the eventual elimination of misfolded glycoproteins in yeast and mammalian cells are reviewed.
Topics: Endoplasmic Reticulum; Glycoproteins; Glycosylation; Mannose; Oligosaccharides; Protein Folding; Protein Processing, Post-Translational; Proteins; alpha-Glucosidases
PubMed: 21340671
DOI: 10.1007/s10059-010-0159-z -
The Journal of Biological Chemistry 2021Levansucrases (LSs) synthesize levan, a β2-6-linked fructose polymer, by successively transferring the fructosyl moiety from sucrose to a growing acceptor molecule....
Levansucrases (LSs) synthesize levan, a β2-6-linked fructose polymer, by successively transferring the fructosyl moiety from sucrose to a growing acceptor molecule. Elucidation of the levan polymerization mechanism is important for using LSs in the production of size-defined products for application in the food and pharmaceutical industries. For a deeper understanding of the levan synthesis reaction, we determined the crystallographic structure of Bacillus subtilis LS (SacB) in complex with a levan-type fructooligosaccharide and utilized site-directed mutagenesis to identify residues involved in substrate binding. The presence of a levanhexaose molecule in the central catalytic cavity allowed us to identify five substrate-binding subsites (-1, +1, +2, +3, and +4). Mutants affecting residues belonging to the identified acceptor subsites showed similar substrate affinity (Km) values to the wildtype (WT) Km value but had a lower turnover number and transfructosylation/hydrolysis ratio. Of importance, compared with the WT, the variants progressively yielded smaller-sized low-molecular-weight levans, as the affected subsites that were closer to the catalytic site, but without affecting their ability to synthesized high-molecular-weight levans. Furthermore, an additional oligosaccharide-binding site 20 Å away from the catalytic pocket was identified, and its potential participation in the elongation mechanism is discussed. Our results clarify, for the first time, the interaction of the enzyme with an acceptor/product oligosaccharide and elucidate the molecular basis of the nonprocessive levan elongation mechanism of LSs.
Topics: Bacillus subtilis; Bacterial Proteins; Crystallography, X-Ray; Hexosyltransferases; Models, Molecular; Oligosaccharides; Protein Conformation
PubMed: 33303628
DOI: 10.1074/jbc.RA120.015853 -
Molecules (Basel, Switzerland) May 2023Galectins are carbohydrate-binding lectins that modulate the proliferation, apoptosis, adhesion, or migration of cells by cross-linking glycans on cell membranes or...
Galectins are carbohydrate-binding lectins that modulate the proliferation, apoptosis, adhesion, or migration of cells by cross-linking glycans on cell membranes or extracellular matrix components. Galectin-4 (Gal-4) is a tandem-repeat-type galectin expressed mainly in the epithelial cells of the gastrointestinal tract. It consists of an N- and a C-terminal carbohydrate-binding domain (CRD), each with distinct binding affinities, interconnected with a peptide linker. Compared to other more abundant galectins, the knowledge of the pathophysiology of Gal-4 is sparse. Its altered expression in tumor tissue is associated with, for example, colon, colorectal, and liver cancers, and it increases in tumor progression, and metastasis. There is also very limited information on the preferences of Gal-4 for its carbohydrate ligands, particularly with respect to Gal-4 subunits. Similarly, there is virtually no information on the interaction of Gal-4 with multivalent ligands. This work shows the expression and purification of Gal-4 and its subunits and presents a structure-affinity relationship study with a library of oligosaccharide ligands. Furthermore, the influence of multivalency is demonstrated in the interaction with a model lactosyl-decorated synthetic glycoconjugate. The present data may be used in biomedical research for the design of efficient ligands of Gal-4 with diagnostic or therapeutic potential.
Topics: Humans; Galectin 4; Galectins; Oligosaccharides; Carbohydrates; Neoplasms; Ligands
PubMed: 37241779
DOI: 10.3390/molecules28104039