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1.
Org Biomol Chem ; 22(19): 3986-3994, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38695061

ABSTRACT

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antiviral Agents , Microwaves , Polysaccharides , SARS-CoV-2 , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Chlorocebus aethiops , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/chemistry , Vero Cells , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemical synthesis , Humans , Animals , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Hexuronic Acids/chemical synthesis , Sulfates/chemistry , Sulfates/pharmacology , Sulfates/chemical synthesis , COVID-19 Drug Treatment , Structure-Activity Relationship
2.
Int J Biol Macromol ; 267(Pt 1): 131506, 2024 May.
Article in English | MEDLINE | ID: mdl-38604422

ABSTRACT

Marine green algae produce sulfated polysaccharides with diverse structures and a wide range of biological activities. This study aimed to enhance the biotechnological potential of sulfated heterorhamnan (Gb1) from Gayralia brasiliensis by chemically modifying it for improved or new biological functions. Using controlled Smith Degradation (GBS) and O-alkylation with 3-chloropropylamine, we synthesized partially water-soluble amine derivatives. GBS modification increase sulfate groups (29.3 to 37.5 %) and α-l-rhamnose units (69.9 to 81.2 mol%), reducing xylose and glucose, compared to Gb1. The backbone featured predominantly 3- and 2-linked α-l-rhamnosyl and 2,3- linked α-l-rhamnosyl units as branching points. Infrared and NMR analyses confirmed the substitution of hydroxyl groups with aminoalkyl groups. The modified compounds, GBS-AHCs and GBS-AHK, exhibited altered anticoagulant properties. GBS-AHCs showed reduced effectiveness in the APTT assay, while GBS-AHK maintained a similar anticoagulant activity level to Gb1 and GBS. Increased nitrogen content and N-alkylation in GBS-AHCs compared to GBS-AHK may explain their structural differences. The chemical modification proposed did not enhance its anticoagulant activity, possibly due to the introduction of amino groups and a positive charge to the polymer. This characteristic presents new opportunities for investigating the potential of these polysaccharides in various biological applications, such as antimicrobial and antitumoral activities.


Subject(s)
Anticoagulants , Chlorophyta , Mannans , Seaweed , Sulfates , Anticoagulants/pharmacology , Anticoagulants/chemistry , Anticoagulants/chemical synthesis , Chlorophyta/chemistry , Seaweed/chemistry , Sulfates/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemical synthesis , Humans , Deoxy Sugars/chemistry , Deoxy Sugars/pharmacology
3.
Acc Chem Res ; 57(11): 1577-1594, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38623919

ABSTRACT

ConspectusCarbohydrates are called the third chain of life. Carbohydrates participate in many important biochemical functions in living species, and the biological information carried by them is several orders of magnitude larger than that of nucleic acids and proteins. However, due to the intrinsic complexity and heterogeneity of carbohydrate structures, furnishing pure and structurally well-defined glycans for functional studies is a formidable task, especially for homogeneous large-size glycans. To address this issue, we have developed a donor preactivation-based one-pot glycosylation strategy enabling multiple sequential glycosylations in a single reaction vessel.The donor preactivation-based one-pot glycosylation refers to the strategy in which the glycosyl donor is activated in the absence of a glycosyl acceptor to generate a reactive intermediate. Subsequently, the glycosyl acceptor with the same anomeric leaving group is added, leading to a glycosyl coupling reaction, which is then iterated to rapidly achieve the desired glycan in the same reactor. The advantages of this strategy include the following: (1) unique chemoselectivity is obtained after preactivation; (2) it is independent of the reactivity of glycosyl donors; (3) multiple-step glycosylations are enabled without the need for intermediate purification; (4) only stoichiometric building blocks are required without complex protecting group manipulations. Using this protocol, a range of glycans including tumor-associated carbohydrate antigens, various glycosaminoglycans, complex N-glycans, and diverse bacterial glycans have been synthesized manually. Gratifyingly, the synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units has been achieved, which created a precedent in the field of polysaccharide synthesis. Recently, the synthesis of a highly branched arabinogalactan from traditional Chinese medicine featuring 140 monosaccharide units has been also accomplished to evaluate its anti-pancreatic-cancer activity. In the spirit of green and sustainable chemistry, this strategy can also be applied to light-driven glycosylation reactions, where either UV or visible light can be used for the activation of glycosyl donors.Automated synthesis is an advanced approach to the construction of complex glycans. Based on the two preactivation modes (general promoter activation mode and light-induced activation mode), a universal and highly efficient automated solution-phase synthesizer was further developed to drive glycan assembly from manual to automated synthesis. Using this synthesizer, a library of oligosaccharides covering various glycoforms and glycosidic linkages was assembled rapidly, either in a general promoter-activation mode or in a light-induced-activation mode. The automated synthesis of a fully protected fondaparinux pentasaccharide was realized on a gram scale. Furthermore, the automated synthesis of large-size polysaccharides was performed, allowing the assembly of arabinans up to an astonishing 1080-mer using the automated multiplicative synthesis strategy, taking glycan synthesis to a new height far beyond the synthesis of nucleic acids (up to 200-mer) and proteins (up to 472-mer).


Subject(s)
Polysaccharides , Polysaccharides/chemistry , Polysaccharides/chemical synthesis , Glycosylation , Automation
4.
Biopolymers ; 115(3): e23574, 2024 May.
Article in English | MEDLINE | ID: mdl-38469937

ABSTRACT

Nucleophilic moieties in polysaccharides (PS) with distinct higher reactivity compared with the hydroxy group are interesting for sustainable applications in chemistry, medicine, and pharmacy. An efficient heterogeneous method for the formation of such nucleophilic PS is described. Employing alcohols as slurry medium, protonated carboxymethyl (CM) PS and hydrazine hydrate are allowed to react at elevated temperatures. The CM derivatives of starch and pullulan can be transformed almost quantitatively to the corresponding hydrazides. The reaction is less efficient for CM dextrans and CM xylans. As slurry media, 2-propanol and ethanol were probed, and the results are compared with a homogeneous procedure performed in water. Overall, the heterogeneous procedure is superior compared with the homogeneous route. 2-Propanol is the best slurry medium investigated yielding PS hydrazides with the highest nitrogen content.


Subject(s)
Hydrazines , Polysaccharides , Hydrazines/chemistry , Polysaccharides/chemistry , Polysaccharides/chemical synthesis , Glucans/chemistry , Glucans/chemical synthesis , Starch/chemistry , Starch/analogs & derivatives , Starch/chemical synthesis , 2-Propanol/chemistry , Dextrans/chemistry , Dextrans/chemical synthesis , Ethanol/chemistry , Xylans/chemistry
5.
J Med Chem ; 65(8): 5975-5989, 2022 04 28.
Article in English | MEDLINE | ID: mdl-35427125

ABSTRACT

Galectin-3 is a ß-galactoside-specific, carbohydrate-recognizing protein (lectin) that is strongly implicated in cancer development, metastasis, and drug resistance. Galectin-3 promotes migration and ability to withstand drug treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Due to high amino acid conservation among galectins and the shallow nature of their glycan-binding site, the design of selective potent antagonists targeting galectin-3 is challenging. Herein, we report the design and synthesis of novel taloside-based antagonists of galectin-3 with enhanced affinity and selectivity. The molecules were optimized by in silico docking, selectivity was established against four galectins, and the binding modes were confirmed by elucidation of X-ray crystal structures. Critically, the specific inhibition of galectin-3-induced BCP-ALL cell agglutination was demonstrated. The compounds decreased the viability of ALL cells even when grown in the presence of protective stromal cells. We conclude that these compounds are promising leads for therapeutics, targeting the tumor-supportive activities of galectin-3 in cancer.


Subject(s)
Antineoplastic Agents , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Binding Sites , Drug Design , Galectin 3/antagonists & inhibitors , Galectin 3/metabolism , Humans , Polysaccharides/chemical synthesis , Polysaccharides/chemistry , Polysaccharides/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism
6.
Chem Pharm Bull (Tokyo) ; 70(2): 155-161, 2022.
Article in English | MEDLINE | ID: mdl-35110436

ABSTRACT

Exopolysaccharides (EPSs) occur widely in natural products made by bacteria, fungi and algae. Some EPSs have intriguing biological properties such as anticancer and immunomodulatory activities. Our group has recently found that EPSs generated from Leuconostoc mesenteroides ssp. mesenteroides strain NTM048 (NTM048 EPS) enhanced a production of mucosal immunoglobulin A (IgA) of mouse. Herein, we described the synthesis and evaluation of the tetrasaccharide fragments of NTM048 EPS to obtain information about the molecular mechanism responsible for the IgA-inducing activity.


Subject(s)
Biological Products/chemical synthesis , Biological Products/metabolism , Leuconostoc/chemistry , Polysaccharides/biosynthesis , Polysaccharides/chemical synthesis , Biological Products/chemistry , Carbohydrate Conformation , Leuconostoc/metabolism , Polysaccharides/chemistry
7.
Carbohydr Polym ; 275: 118743, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34742445

ABSTRACT

Polysaccharide/MOF composite membranes have captured the interests of many researchers during decontamination of polluted environments. Their popularity can be attributed to the relatively high chemical and thermal stabilities of these composite membranes. Chitosan is among the polysaccharides extensively used during the synthesis of hybrid membranes with MOFs. The applications of chitosan/MOF composite membranes in separation science are explored in detail in this paper. Researchers have also synthesised mixed matrix membranes of MOFs with cellulose and cyclodextrin that have proved to be effective during separation of a variety of materials. The uses of cellulose/MOF and cyclodextrin/MOF membranes for the removal of environmental pollutants are discussed in this review. In addition, the challenges associated with the use of these mixed matrix membranes are explored in this current paper.


Subject(s)
Environmental Pollutants/isolation & purification , Metal-Organic Frameworks/chemistry , Polysaccharides/chemistry , Carbohydrate Conformation , Environmental Pollutants/chemistry , Metal-Organic Frameworks/chemical synthesis , Polysaccharides/chemical synthesis
8.
Carbohydr Polym ; 277: 118796, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34893224

ABSTRACT

Extraintestinal pathogenic Escherichia coli O1 is a frequently identified serotype that causes serious infections and is often refractory to antimicrobial therapy. Glycoconjugate vaccine represents a promising measure to reduce ExPEC infections. Herein, we designed an O1-specific glyco-optimized chassis strain for manufacture of O-polysaccharide (OPS) antigen and OPS-based bioconjugate. Specifically, OPS and OPS-based glycoprotein were synthesized in glyco-optimized chassis strain, when compared to the unmeasurable level of the parent strain. The optimal expression of oligosaccharyltransferase and carrier protein further improved the titer. MS analysis elucidated the correct structure of resulting bioconjugate at routine and unreported glycosylation sequons of carrier protein, with a higher glycosylation efficiency. Finally, purified bioconjugate stimulated mouse to generate specific IgG antibodies and protected them against virulent ExPEC O1 challenge. The plug-and-play glyco-optimized platform is suitable for bioconjugate synthesis, thus providing a potential platform for future medical applications.


Subject(s)
Anti-Bacterial Agents/pharmacology , Extraintestinal Pathogenic Escherichia coli/drug effects , Glycoconjugates/pharmacology , Polysaccharides/pharmacology , Protein Engineering , Vaccines, Conjugate/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Drug Development , Female , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Mice , Microbial Sensitivity Tests , Polysaccharides/chemical synthesis , Polysaccharides/chemistry , Vaccines, Conjugate/chemistry
9.
Molecules ; 26(23)2021 Nov 30.
Article in English | MEDLINE | ID: mdl-34885873

ABSTRACT

Organocatalysis is a very useful tool for the asymmetric synthesis of biologically or pharmacologically active compounds because it avoids the use of noxious metals, which are difficult to eliminate from the target products. Moreover, in many cases, the organocatalysed reactions can be performed in benign solvents and do not require anhydrous conditions. It is well-known that most of the above-mentioned reactions are promoted by a simple aminoacid, l-proline, or, to a lesser extent, by the more complex cinchona alkaloids. However, during the past three decades, other enantiopure natural compounds, the carbohydrates, have been employed as organocatalysts. In the present exhaustive review, the detailed preparation of all the sugar-based organocatalysts as well as their catalytic properties are described.


Subject(s)
Carbohydrates/chemical synthesis , Carbohydrates/chemistry , Catalysis , Epoxy Compounds/chemistry , Monosaccharides/chemical synthesis , Monosaccharides/chemistry , Oxidation-Reduction , Polysaccharides/chemical synthesis , Polysaccharides/chemistry
10.
ACS Chem Biol ; 16(10): 2016-2025, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34649433

ABSTRACT

While the improved treatment of human immunodeficiency virus type 1 (HIV-1) infection is available, the development of an effective and safe prophylactic vaccine against HIV-1 is still an unrealized goal. Encouragingly, the discovery of broadly neutralizing antibodies (bNAbs) from HIV-1 positive patients that are capable of neutralizing a broad spectrum of HIV-1 isolates of various clades has accelerated the progress of vaccine development in the past few years. Some of these bNAbs recognize the N-glycans on the viral surface gp120 glycoprotein. We have been interested in using the glycan epitopes recognized by bNAbs for the development of vaccines to elicit bNAb-like antibodies with broadly neutralizing activities. Toward this goal, we have identified novel hybrid-type structures with subnanomolar avidity toward several bNAbs including PG16, PGT121, PGT128-3C, 2G12, VRC13, VRC-PG05, VRC26.25, VRC26.09, PGDM1400, 35O22, and 10-1074. Here, we report the immunogenicity evaluation of a novel hybrid glycan conjugated to carrier DTCRM197, a nontoxic mutant of the diphtheria toxin, for immunization in mice. Our results indicated that the IgG response was mainly against the chitobiose motif with nonspecific binding to a panel of N-glycans with reducing end GlcNAc-GlcNAc (chitobiose) printed on the glass slides. However, the IgM response was mainly toward the reducing end GlcNAc moiety. We further used the glycoconjugates of Man3GlcNAc2, Man5GlcNAc2, and Man9GlcNAc2 glycans for immunization, and a similar specificity pattern was observed. These findings suggest that the immunogenicity of chitobiose may interfere with the outcome of N-glycan-based vaccines, and modification may be necessary to increase the immunogenicity of the entire N-glycan epitope.


Subject(s)
AIDS Vaccines/immunology , Broadly Neutralizing Antibodies/immunology , Glycoconjugates/immunology , HIV Antibodies/immunology , Polysaccharides/immunology , Acetylglucosamine/immunology , Animals , Bacterial Proteins/chemistry , Carbohydrate Sequence , Disaccharides/immunology , Epitopes , Female , Glycoconjugates/chemical synthesis , HIV-1/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Mice, Inbred C57BL , Polysaccharides/chemical synthesis , Vaccine Development
11.
Biomed Pharmacother ; 144: 112332, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34673422

ABSTRACT

Polysaccharides have anti-virus, anti-cancer, anti-oxidation, immune regulation, hypoglycemia and other biological activities. Because of their safety, fewer side effects and other advantages, polysaccharides are considered as ideal raw materials in food and drugs. The biological activity of polysaccharides can be improved by structural modification (such as sulfation, carboxymethylation, phosphorylation, etc.), and even new biological activity can be generated. In this review, the recent advances in the phosphorylation of polysaccharides were reviewed from the perspectives of modification methods, structures, biological activities and structure-activity relationships.


Subject(s)
Esters/chemical synthesis , Esters/pharmacology , Polysaccharides/chemical synthesis , Polysaccharides/pharmacology , Animals , Esters/toxicity , Humans , Molecular Structure , Phosphorylation , Polysaccharides/toxicity , Structure-Activity Relationship
12.
Carbohydr Res ; 510: 108443, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34597980

ABSTRACT

Electrospinning has become an inevitable approach to produce nanofibrous structures for diverse environmental applications. Polysaccharides, due to their variety of types, biobased origins, and eco-friendly, and renewable nature are wonderful materials for the said purpose. The present review discusses the electrospinning process, the parameters involved in the formation of electrospun nanofibers in general, and the polysaccharides in specific. The selection of materials to be electrospun depends on the processing conditions and properties deemed desirable for specific applications. Thereby, the conditions to electrospun polysaccharides-based nanofibers have been focused on for possible environmental applications including air filtration, water treatment, antimicrobial treatment, environmental sensing, and so forth. The polysaccharide-based electrospun membranes, for instance, due to their active adsorption sites could find significant potential for contaminants removal from the aqueous systems. The study also gives some recommendations to overcome any shortcomings faced during the electrospinning and environmental applications of polysaccharide-based matrices.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Environmental Microbiology , Nanofibers/chemistry , Polysaccharides/pharmacology , Water Pollutants, Chemical/isolation & purification , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Carbohydrate Conformation , Microbial Sensitivity Tests , Polysaccharides/chemical synthesis , Polysaccharides/chemistry , Water Pollutants, Chemical/chemistry , Water Purification
13.
ACS Chem Biol ; 16(10): 1908-1916, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34506714

ABSTRACT

Metabolic glycan probes have emerged as an excellent tool to investigate vital questions in biology. Recently, methodology to incorporate metabolic bacterial glycan probes into the cell wall of a variety of bacterial species has been developed. In order to improve this method, a scalable synthesis of the peptidoglycan precursors is developed here, allowing for access to essential peptidoglycan immunological fragments and cell wall building blocks. The question was asked if masking polar groups of the glycan probe would increase overall incorporation, a common strategy exploited in mammalian glycobiology. Here, we show, through cellular assays, that E. coli do not utilize peracetylated peptidoglycan substrates but do employ methyl esters. The 10-fold improvement of probe utilization indicates that (i) masking the carboxylic acid is favorable for transport and (ii) bacterial esterases are capable of removing the methyl ester for use in peptidoglycan biosynthesis. This investigation advances bacterial cell wall biology, offering a prescription on how to best deliver and utilize bacterial metabolic glycan probes.


Subject(s)
Molecular Probes/metabolism , Muramic Acids/metabolism , Peptidoglycan/metabolism , Polysaccharides/metabolism , Cell Wall/metabolism , Escherichia coli/metabolism , Molecular Probes/chemical synthesis , Muramic Acids/chemical synthesis , Polysaccharides/chemical synthesis
14.
Angew Chem Int Ed Engl ; 60(46): 24686-24693, 2021 11 08.
Article in English | MEDLINE | ID: mdl-34520098

ABSTRACT

The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds. Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate. Furthermore, high α-selectivity of these glycosylation reactions was realized by utilizing remote participation. Two asymmetrically deuterium labeled sialyl N-glycans were also synthesized by the same strategy. The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition. The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch. Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.


Subject(s)
Neuraminidase/metabolism , Polysaccharides/chemical synthesis , Deuterium/chemistry , Glycosylation , Influenza A Virus, H1N1 Subtype/enzymology , Mass Spectrometry/methods , Polysaccharides/analysis , Polysaccharides/metabolism , Sialic Acids/analysis , Sialic Acids/metabolism , Spectrophotometry, Ultraviolet
15.
Carbohydr Polym ; 271: 118449, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34364583

ABSTRACT

Fucoidans are a class of sulfated fucose-containing bioactive polysaccharides produced by brown algae. The biological effects exhibited by fucoidans are thought to be related to their sulfation. However, the lack of methods for sulfation control does not allow for a reliable conclusion about the influence of the position of certain sulfate groups on the observed biological effects. We identified the gene encoding the endo-acting fucoidan sulfatase swf5 in the marine bacterium Wenyingzhuangia fucanilytica CZ1127T. This is the first report on the sequence of fucoidan endo-sulfatase. Sulfatase SWF5 belongs to the subfamily S1_22 of the family S1. SWF5 was shown to remove 4O-sulfation in fucoidans composed from the alternating α-(1→3)- and α-(1→4)-linked residues of sulfated L-fucose but not from fucoidans with the α-(1→3)-linked backbone. The endo-sulfatase was used to selectively prepare 4O-desulfated fucoidan derivatives. It was shown that the 4O-desulfated fucoidans inhibit colony formation of DLD-1 and MCF-7 cells less effectively than unmodified fucoidans. Presumably, 4O-sulfation makes a significant contribution to the anticancer activity of fucoidans.


Subject(s)
Antineoplastic Agents/pharmacology , Polysaccharides/pharmacology , Sulfatases/chemistry , Amino Acid Sequence , Antineoplastic Agents/chemical synthesis , Bacterial Proteins/chemistry , Bacterial Proteins/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Flavobacteriaceae/enzymology , Humans , Molecular Structure , Polysaccharides/chemical synthesis , Substrate Specificity , Sulfatases/isolation & purification
16.
Mar Drugs ; 19(6)2021 Jun 16.
Article in English | MEDLINE | ID: mdl-34208540

ABSTRACT

Marine biomass is a treasure trove of materials. Marine polysaccharides have the characteristics of biocompatibility, biodegradability, non-toxicity, low cost, and abundance. An enormous variety of polysaccharides can be extracted from marine organisms such as algae, crustaceans, and microorganisms. The most studied marine polysaccharides include chitin, chitosan, alginates, hyaluronic acid, fucoidan, carrageenan, agarose, and Ulva. Marine polysaccharides have a wide range of applications in the field of biomedical materials, such as drug delivery, tissue engineering, wound dressings, and sensors. The drug delivery system (DDS) can comprehensively control the distribution of drugs in the organism in space, time, and dosage, thereby increasing the utilization efficiency of drugs, reducing costs, and reducing toxic side effects. The nano-drug delivery system (NDDS), due to its small size, can function at the subcellular level in vivo. The marine polysaccharide-based DDS combines the advantages of polysaccharide materials and nanotechnology, and is suitable as a carrier for different pharmaceutical preparations. This review summarizes the advantages and drawbacks of using marine polysaccharides to construct the NDDS and describes the preparation methods and modification strategies of marine polysaccharide-based nanocarriers.


Subject(s)
Aquatic Organisms/chemistry , Biological Products , Nanoparticle Drug Delivery System , Polysaccharides , Animals , Biological Products/chemical synthesis , Biological Products/chemistry , Biological Products/isolation & purification , Humans , Nanoparticle Drug Delivery System/chemical synthesis , Nanoparticle Drug Delivery System/chemistry , Nanoparticle Drug Delivery System/isolation & purification , Polysaccharides/chemical synthesis , Polysaccharides/chemistry , Polysaccharides/isolation & purification
17.
Chem Biodivers ; 18(9): e2100338, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34296822

ABSTRACT

AIDS, caused by HIV-1, is one of the most dangerous infectious diseases in the world. Therefore, it is necessary to develop new drugs with more potent bioactivities, less toxicity and higher tolerability for controlling the viral load, particularly by using the raw materials that are widely available. Agaricus blazei Murill (AbM), known in China as jisongrong, is of great importance as a food source and as a health-promoting supplement for immunomodulation. The polysaccharides of AbM exhibit various biological activities, such as regulating cellular immunity and providing anti-oxidative, anti-infective, and anti-inflammatory effects. At present, to our knowledge, no report has explored the chemically sulfated and anti-HIV-1 activity of AbM polysaccharides. Herein, the sulfated AbM polysaccharides with different sulfur contents were prepared by the chlorosulfonic acid-pyridine method. The characteristics of sulfated derivatives were established by the determination of the sulfur content, the relative molecular weight, and the Fourier-transform infrared spectroscopy. The anti-HIV activities of the sulfated AbM polysaccharides were evaluated by CCK-8 and the single-cycle pseudovirus infection (TZM-bl) assay. The sulfated AbM polysaccharides had strong antiviral properties, and the half-maximal inhibitory concentrations approached that of the positive control, azidothymidine. Sulfated modification of AbM polysaccharides can increase their anti-HIV pharmacological activity, which makes them promising alternative candidates as bioactive macromolecules for biomedical applications in HIV/AIDS.


Subject(s)
Agaricus/chemistry , Anti-HIV Agents/pharmacology , HIV/drug effects , Polysaccharides/pharmacology , Sulfates/chemistry , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Carbohydrate Conformation , Microbial Sensitivity Tests , Polysaccharides/chemical synthesis , Polysaccharides/chemistry
18.
Angew Chem Int Ed Engl ; 60(35): 19287-19296, 2021 08 23.
Article in English | MEDLINE | ID: mdl-34124805

ABSTRACT

The importance of multivalency for N-glycan-protein interactions has primarily been studied by attachment of minimal epitopes to artificial multivalent scaffold and not in the context of multi-antennary glycans. N-glycans can be modified by bisecting GlcNAc, core xylosides and fucosides, and extended N-acetyl lactosamine moieties. The impact of such modifications on glycan recognition are also not well understood. We describe here a chemoenzymatic methodology that can provide N-glycans expressed by the parasitic worm S. mansoni having unique epitopes at each antenna and containing core xyloside. NMR, computational and electron microscopy were employed to investigate recognition of the glycans by the human lectin DC-SIGN. It revealed that core xyloside does not influence terminal epitope recognition. The multi-antennary glycans bound with higher affinity to DC-SIGN compared to mono-valent counterparts, which was attributed to proximity-induced effective concentration. The multi-antennary glycans cross-linked DC-SIGN into a dense network, which likely is relevant for antigen uptake and intracellular routing.


Subject(s)
Epitopes/chemistry , Lectins/analysis , Polysaccharides/chemistry , Schistosoma mansoni/chemistry , Animals , Humans , Polysaccharides/chemical synthesis
19.
Carbohydr Polym ; 267: 118161, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34119135

ABSTRACT

In this study we described the synthesis of a hybrid polysaccharide harboring moieties of ulvan and kappa-carrabiose. Alkylamines (1,3-diaminopropane and 1,6-diaminohexane) were selectively inserted into ß-D-GlcAp and α-L-IdoAp units in the ulvan structure via an amide bond formation producing ulvan-amide derivatives F-DAP (N% = 1.77; Mw = 208 kg mol-1) and F-DAH (N% = 1.77; Mw = 202 kg mol-1), which were reacted with kappa-carrabiose via reductive amination to produce hybrid ulvan-kappa-carrabiose polysaccharides F-DAP-Kb (N% = 1.56; Mw = 206 kg mol-1) and F-DAH-Kb (N% = 1.16; Mw = 200 kg mol-1). All the ulvan derivatives were characterized by 1H and 13C NMR spectroscopy and did not show cytotoxicity against human dermal fibroblasts (HDFa) at the concentrations of 25, 100, and 500 µg mL-1, neither anticoagulant properties at the range of 10-150 µg mL-1. Therefore, the ulvan-amide derivatives and the hybrid ulvan-kappa-carrabiose polysaccharides showed good biocompatibility in vitro, presenting as worthy candidates for tailoring scaffolds for biomedical applications.


Subject(s)
Anticoagulants/pharmacology , Carrageenan/pharmacology , Polysaccharides/pharmacology , Anticoagulants/chemical synthesis , Anticoagulants/toxicity , Carrageenan/chemical synthesis , Carrageenan/toxicity , Fibroblasts/drug effects , Humans , Partial Thromboplastin Time , Polysaccharides/chemical synthesis , Polysaccharides/toxicity
20.
Front Immunol ; 12: 668217, 2021.
Article in English | MEDLINE | ID: mdl-34093565

ABSTRACT

Obesity is the largest risk factor for the development of chronic diseases in industrialized countries. Excessive fat accumulation triggers a state of chronic low-grade inflammation to the detriment of numerous organs. To address this problem, our lab has been examining the anti-inflammatory mechanisms of two human milk oligosaccharides (HMOs), lacto-N-fucopentaose III (LNFPIII) and lacto-N-neotetraose (LNnT). LNFPIII and LNnT are HMOs that differ in structure via presence/absence of an α1,3-linked fucose. We utilize LNFPIII and LNnT in conjugate form, where 10-12 molecules of LNFPIII or LNnT are conjugated to a 40 kDa dextran carrier (P3DEX/NTDEX). Previous studies from our lab have shown that LNFPIII conjugates are anti-inflammatory, act on multiple cell types, and are therapeutic in a wide range of murine inflammatory disease models. The α1,3-linked fucose residue on LNFPIII makes it difficult and more expensive to synthesize. Therefore, we asked if LNnT conjugates induced similar therapeutic effects to LNFPIII. Herein, we compare the therapeutic effects of P3DEX and NTDEX in a model of diet-induced obesity (DIO). Male C57BL/6 mice were placed on a high-fat diet for six weeks and then injected twice per week for eight weeks with 25µg of 40 kDa dextran (DEX; vehicle control), P3DEX, or NTDEX. We found that treatment with P3DEX, but not NTDEX, led to reductions in body weight, adipose tissue (AT) weights, and fasting blood glucose levels. Mice treated with P3DEX also demonstrated improvements in glucose homeostasis and insulin tolerance. Treatment with P3DEX or NTDEX also induced different profiles of serum chemokines, cytokines, adipokines, and incretin hormones, with P3DEX notably reducing circulating levels of leptin and resistin. P3DEX also reduced WAT inflammation and hepatic lipid accumulation, whereas NTDEX seemed to worsen these parameters. These results suggest that the small structural difference between P3DEX and NTDEX has significant effects on the conjugates' therapeutic abilities. Future work will focus on identifying the receptors for these conjugates and delineating the mechanisms by which P3DEX and NTDEX exert their effects.


Subject(s)
Amino Sugars/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Obesity Agents/pharmacology , Diet, High-Fat , Milk, Human , Obesity/prevention & control , Oligosaccharides/pharmacology , Polysaccharides/pharmacology , Adipokines/blood , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/physiopathology , Adiposity/drug effects , Amino Sugars/chemical synthesis , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Obesity Agents/chemical synthesis , Blood Glucose/drug effects , Blood Glucose/metabolism , Cytokines/blood , Disease Models, Animal , Inflammation Mediators/blood , Insulin Resistance , Male , Mice, Inbred C57BL , Milk, Human/chemistry , Molecular Structure , Obesity/blood , Obesity/etiology , Obesity/physiopathology , Oligosaccharides/chemical synthesis , Polysaccharides/chemical synthesis , Structure-Activity Relationship , Weight Gain/drug effects
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