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Bioproduction and applications of aldobionic acids with a focus on maltobionic and cellobionic acid.Bioprocess and Biosystems Engineering Jul 2023Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications... (Review)
Review
Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications such as food and beverages, pharmaceuticals and medicine, cosmetics or chemical processes. During the last decade, all these industries are observing a shift of consumer preferences towards plant-based options. Thus, the biotechnological industry is trying to replace the animal-derived LBA. Maltobionic acid (MBA) and cellobionic acid (CBA) are two stereoisomers of LBA which have emerged as vegan alternatives. However, MBA and CBA face different obstacles related to their industrial production. While traditionally used electrochemical or chemical catalysis often rely on cost intensive and/or hazardous catalysts, novel production methods with microorganisms are still poorly studied. In the first part, this paper discusses both alternatives in terms of their characteristics and applications. In the second part, it reviews the long-studied chemical production and the novel bioproduction methods, which are based on enzymatic and microbial systems. This review concludes with a discussion of future work needed to bring their production to the industrial scale.
Topics: Animals; Disaccharides; Biotechnology
PubMed: 37058246
DOI: 10.1007/s00449-023-02872-7 -
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 -
Biomacromolecules Jun 2021Antifreeze glycoproteins (AFGPs) are able to bind to ice, halt its growth, and are the most potent inhibitors of ice recrystallization known. The structural basis for...
Antifreeze glycoproteins (AFGPs) are able to bind to ice, halt its growth, and are the most potent inhibitors of ice recrystallization known. The structural basis for AFGP's unique properties remains largely elusive. Here we determined the antifreeze activities of AFGP variants that we constructed by chemically modifying the hydroxyl groups of the disaccharide of natural AFGPs. Using nuclear magnetic resonance, two-dimensional infrared spectroscopy, and circular dichroism, the expected modifications were confirmed as well as their effect on AFGPs solution structure. We find that the presence of all the hydroxyls on the disaccharides is a requirement for the native AFGP hysteresis as well as the maximal inhibition of ice recrystallization. The saccharide hydroxyls are apparently as important as the acetyl group on the galactosamine, the α-linkage between the disaccharide and threonine, and the methyl groups on the threonine and alanine. We conclude that the use of hydrogen-bonding through the hydroxyl groups of the disaccharide and hydrophobic interactions through the polypeptide backbone are equally important in promoting the antifreeze activities observed in the native AFGPs. These important criteria should be considered when designing synthetic mimics.
Topics: Antifreeze Proteins; Disaccharides; Glycoproteins; Hydrogen Bonding; Ice; Magnetic Resonance Spectroscopy
PubMed: 33957041
DOI: 10.1021/acs.biomac.1c00313 -
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 -
Angewandte Chemie (International Ed. in... Mar 2020C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics. We demonstrate that activating a hemiacetal with a sulfonyl...
C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics. We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides. This reaction tolerates a range of acceptors and donors, including disaccharides. The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
Topics: Alkylation; Disaccharides; Glycoconjugates; Glycosides; Glycosylation; Molecular Structure; Stereoisomerism; Sulfinic Acids
PubMed: 31880395
DOI: 10.1002/anie.201914221 -
Gut Microbes 2021Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized...
Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto--biose (LNB) and galacto--biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased ( and ) or decreased ( and ) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of genus in both fucosyl-oligosaccharides. An increment of the relative abundance of genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of , whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species and were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.
Topics: Acetates; Adult; Animals; Bacteria; Butyrates; DNA, Bacterial; Disaccharides; Feces; Female; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn; Male; Mice; Mice, Inbred C57BL; Milk, Human; RNA, Ribosomal, 16S; Young Adult
PubMed: 33938391
DOI: 10.1080/19490976.2021.1914377 -
Drugs Jun 1997Lactulose is one of the most frequently utilised agents in the treatment of constipation and hepatic encephalopathy because of its efficacy and good safety profile. The... (Review)
Review
Lactulose is one of the most frequently utilised agents in the treatment of constipation and hepatic encephalopathy because of its efficacy and good safety profile. The key to understanding the possible modes of action by which lactulose achieves its therapeutic effects in these disorders lies in certain pharmacological phenomena: (a) lactulose is a synthetic disaccharide that does not occur naturally; (b) there is no disaccharidase on the microvillus membrane of enterocytes in the human small intestine that hydrolyses lactulose; and (c) lactulose is not absorbed from the small intestine. Thus, the primary site of action is the colon in which lactulose is readily fermented by the colonic bacterial flora with the production of short-chain fatty acids and various gases. The purpose of this review is to focus on some pertinent basic aspects of the clinical pharmacology of lactulose and to discuss the possible mechanisms by which lactulose benefits patients with constipation and hepatic encephalopathy.
Topics: Animals; Cathartics; Colon; Constipation; Disaccharides; Gastrointestinal Agents; Hepatic Encephalopathy; Humans; Lactulose
PubMed: 9179525
DOI: 10.2165/00003495-199753060-00003 -
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 -
Marine Drugs May 2023The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules...
The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules that are part of the extracellular matrix undergo qualitative and quantitative changes and the effects, such as a loss of skin firmness or wrinkles, can be visible. The changes caused by the aging process do not only affect the surface of the skin, but also extend to skin appendages such as hair follicles. In the present study, the ability of marine-derived saccharides, L-fucose and chondroitin sulphate disaccharide, to support skin and hair health and minimize the effects of intrinsic and extrinsic aging was investigated. The potential of the tested samples to prevent adverse changes in the skin and hair through stimulation of natural processes, cellular proliferation, and production of extracellular matrix components collagen, elastin, or glycosaminoglycans was investigated. The tested compounds, L-fucose and chondroitin sulphate disaccharide, supported skin and hair health, especially in terms of anti-aging effects. The obtained results indicate that both ingredients support and promote the proliferation of dermal fibroblasts and dermal papilla cells, provide cells with a supply of sulphated disaccharide GAG building blocks, increase ECM molecule production (collagen and elastin) by HDFa, and support the growth phase of the hair cycle (anagen).
Topics: Humans; Elastin; Chondroitin Sulfates; Fucose; Cells, Cultured; Skin; Collagen; Fibroblasts; Disaccharides
PubMed: 37367655
DOI: 10.3390/md21060330 -
Scientific Reports Apr 2019Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-,...
Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-, ι-; and λ-carrageenans, including the disaccharides (carrabioses) and disaccharide-alditols (carrabiitols) from seaweed extracts as potential antitumor compounds and identified the active principle of the cytotoxic and potential antitumor properties of these compounds. Both κ and ι-carrageenan, as well as carrageenan oligosaccharides showed cytotoxic effect over LM2 tumor cells. Characterized disaccharides (carrabioses) and the reduced product carrabiitols, were also tested. Only carrabioses were cytotoxic, and among them, κ-carrabiose was the most effective, showing high cytotoxic properties, killing the cells through an apoptotic pathway. In addition, the cells surviving treatment with κ-carrabiose, showed a decreased metastatic ability in vitro, together with a decreased cell-cell and cell-matrix interactions, thus suggesting possible antitumor potential. Overall, our results indicate that most cytotoxic compounds derived from carrageenans have lower molecular weights and sulfate content. Potential applications of the results emerging from the present work include the use of disaccharide units such as carrabioses coupled to antineoplasics in order to improve its cytotoxicity and antimetastatic properties, and the use of ι-carrageenan as adjuvant or carrier in anticancer treatments.
Topics: Animals; Antineoplastic Agents; Biological Products; Carrageenan; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Survival; Disaccharides; Mice; Molecular Structure
PubMed: 31040376
DOI: 10.1038/s41598-019-43238-y