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1.
Chem Soc Rev ; 48(22): 5488-5505, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31552920

RESUMO

Glycans - simple or complex carbohydrates - play key roles as recognition determinants and modulators of numerous physiological and pathological processes. Thus, many biotechnological, diagnostic and therapeutic opportunities abound for molecular recognition entities that can bind glycans with high selectivity and affinity. This review begins with an overview of the current biologically and synthetically derived glycan-binding scaffolds that include antibodies, lectins, aptamers and boronic acid-based entities. It is followed by a more detailed discussion on various aspects of their generation, structure and recognition properties. It serves as the basis for highlighting recent key developments and technical challenges that must be overcome in order to fully deal with the specific recognition of a highly diverse and complex range of glycan structures.


Assuntos
Anticorpos/química , Aptâmeros de Nucleotídeos/química , Ácidos Borônicos/química , Lectinas/química , Polissacarídeos/química , Receptores Artificiais/química , Anticorpos/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Ácidos Borônicos/metabolismo , Humanos , Lectinas/metabolismo , Polissacarídeos/síntese química , Polissacarídeos/metabolismo , Receptores Artificiais/metabolismo
2.
Carbohydr Res ; 485: 107806, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526929

RESUMO

Fucoidan is a unique polysaccharide that has various biological activities partly owing to its capability to act as mimetics of natural ligands of protein receptors. However, its use is limited due to a number of reasons including those associated with molecular weight and composition variation in relation to an algae type and habitat, raw material collection time, extraction method and duration. The main problem which limits its application in therapy is high molecular weight and seasonal composition. To expand the scope of its application, it is necessary to develop a validated procedure of high-molecular-weight fucoidan depolymerization or synthesis of its oligomeric elements . Therefore, there is a need for the synthesis of polysaccharideoligomeric components and/or polymer mimetics which allow for the creation of chains with a certain degree of sulfation, molecular weight and yield. This paper presents the most commonly used methods of fucoidan homopolysaccharide and heteropolysaccharide fragments synthesis as well as problems associated with their synthesis, including fucoidan analogues available in the form of glycopolymers that are obtained by using different methods of radical polymerization. These fucoidan mimetic glycopolymers have a biological activity similar to that of native fucoidans with high yield, which allows for their use as potential agents in the pharmaceutical industry.


Assuntos
Técnicas de Química Sintética/métodos , Polimerização , Polissacarídeos/química , Polissacarídeos/síntese química , Peso Molecular
3.
Int J Nanomedicine ; 14: 3245-3263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190792

RESUMO

Background: Bacterial resistance to antibiotics is one of the biggest challenges facing medicine today. Anti-adhesive therapy, using inhibitors of bacterial adhesion to epithelial cells, one of the first stages of infection, is a promising approximation in this area. The size, shape, number of sugar and their placement are variables that have to be taken into account in order to develop multivalent systems able to inhibit the bacterial adhesion based on sugar-lectin interaction. Materials and methods: In the present work we report a modular approach for the synthesis of water-soluble 1D-carbon nanotube-sugar nanoconstructs, with the necessary flexibility to allow an efficient sugar-lectin interaction. The method is based on the reaction of aryl diazonium salts generated in situ from aniline-substituted mannose and lactose derivatives with single wall carbon nanotubes (SWCNTs) sidewalls. Results: Two hybrid nanosystems, I-II, exposing mannose or lactose and having a tetraethylene glycol spacer between the sugar and the nanotube sidewall were rapidly assembled and adequately characterized. The sweet nano-objects were then tested for their ability to agglutinate and selectively inhibit the growth of uropathogenic Escherichia coli. These studies have shown that nanosystem I, exposing mannose on the nanotube surface is able to agglutinate and to inhibit the bacterial growth unlike nano-objects II exposing lactose. Conclusion: The results reported constitute a proof of principle in using mannose-coated 1D-carbon nanotubes as antiadhesive drugs that compete for FimH binding and prevent the uropathogenic bacteria from adhering to the urothelial surface.


Assuntos
Escherichia coli/citologia , Nanotubos de Carbono/química , Aglutinação , Aderência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Manose/química , Nanotubos de Carbono/ultraestrutura , Polissacarídeos/síntese química , Polissacarídeos/química , Propriedades de Superfície
4.
Molecules ; 24(11)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163700

RESUMO

Polylactic acid (PLA) is limited in its application due to its high price, high brittleness and low glass-transition temperature. Modification methods are currently used to overcome these shortcomings. In this study, Bletilla striata polysaccharide (BSP) was blended with PLA by a solvent method. DMA data showed that the BSP/PLA film had a higher glass-transition temperature, and the glass-transition temperature of the film showed an extreme value of 68 °C when the proportion of the chalk polysaccharide was 0.8%. TG data indicates that the composite film material has good thermal stability. Tensile tests show that the composite film is improved in rigidity and elasticity compared to the pure PLA film. The blending modification of PLA with white peony polysaccharide not only reduces the cost of PLA, but also improves the thermal and mechanical properties of PLA.


Assuntos
Orchidaceae/química , Poliésteres/química , Poliésteres/síntese química , Polissacarídeos/química , Polissacarídeos/síntese química , Varredura Diferencial de Calorimetria , Análise Fatorial , Vidro/química , Resistência à Tração , Termogravimetria , Temperatura de Transição , Difração de Raios X
5.
Curr Med Chem ; 26(35): 6349-6398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203794

RESUMO

Carbohydrates are one of the most powerful and versatile classes of biomolecules that nature uses to regulate organisms' biochemistry, modulating plenty of signaling events within cells, triggering a plethora of physiological and pathological cellular behaviors. In this framework, glycan carrier systems or carbohydrate-decorated materials constitute interesting and relevant tools for medicinal chemistry applications. In the last few decades, efforts have been focused, among others, on the development of multivalent glycoconjugates, biosensors, glycoarrays, carbohydrate-decorated biomaterials for regenerative medicine, and glyconanoparticles. This review aims to provide the reader with a general overview of the different carbohydrate carrier systems that have been developed as tools in different medicinal chemistry approaches relying on carbohydrate-protein interactions. Given the extent of this topic, the present review will focus on selected examples that highlight the advancements and potentialities offered by this specific area of research, rather than being an exhaustive literature survey of any specific glyco-functionalized system.


Assuntos
Química Farmacêutica/métodos , Polissacarídeos/uso terapêutico , Animais , Técnicas Biossensoriais/métodos , Dendrímeros/síntese química , Dendrímeros/metabolismo , Dendrímeros/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/uso terapêutico , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/uso terapêutico , Polissacarídeos/síntese química , Polissacarídeos/metabolismo , Ligação Proteica , Proteínas/metabolismo
6.
Chem Soc Rev ; 48(15): 4006-4018, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31169838

RESUMO

In the pursuit of developing potent drug molecules, more efficient and straightforward procedures are in high demand. The evergrowing interest in carbohydrate-based therapeutics and vaccines particularly calls for such reliable and universal approaches that assemble oligosaccharides rapidly and stereoselectively. Hereby, we compiled remarkable efforts made in exploring the possibilities of protection-less glycosylation strategies. Pioneering works using organotin reagents or catalysts were introduced first, followed by the organoboron successors that were deemed less toxic and more versatile alternatives. In the meantime, more species such as copper or caesium were also included and supported by a mechanistic rationale. Lastly, we hope to bring further insights into the synthesis of intricate carbohydrate derivatives, achieved with the aid of glycosylation methods discussed herein.


Assuntos
Produtos Biológicos/química , Polissacarídeos/química , Açúcares/química , Produtos Biológicos/síntese química , Glicosilação , Estrutura Molecular , Polissacarídeos/síntese química , Estereoisomerismo , Açúcares/síntese química
7.
Int J Biol Macromol ; 132: 970-977, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30965077

RESUMO

Polysaccharides are a major class of biomacromolecules. Their bioactivities depend on chemical structure, which includes monosaccharide composition, linkages below sugar residues, and solution conformation. Many researchers report that chemical modifications of polysaccharides lead to a significantly increase in the structural diversity, promoting bioactivity and even add new bioactivities, including antioxidant and anti-tumor properties as well as anticoagulant and immunoregulatory activities. This paper reviews the recent progress of chemical modification of polysaccharides, including i) the common synthetic methods of chemical modification; ii) their structural characterization; iii) their bioactivities; and iv) the structure activity relationships of these modified polysaccharides. This review also suggests future directions for researchers and new applications for chemically modified polysaccharide derivatives in the pharmaceutical and food industries.


Assuntos
Polissacarídeos/química , Polissacarídeos/síntese química , Animais , Técnicas de Química Sintética , Humanos , Polissacarídeos/farmacologia , Relação Estrutura-Atividade
8.
Int J Biol Macromol ; 133: 964-970, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004636

RESUMO

Porous grafted copolymer with excellent thermal stability and swelling capacity was synthesized from water soluble Prunus cerasifera gum polysaccharide (PG) and acrylamide (AM). The monosaccharide compositions and the structure of Prunus cerasifera tree gum were detected by a high-performance anion exchange chromatography (HPAEC) system and 1H NMR and 13C NMR, and the obtained PG-AM copolymer was characterized by Fourier transform infrared (FT-IR), scanning electron microscope (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), respectively. The results indicated that the water soluble polysaccharides obtained from Prunus cerasifera tree gum were mainly composed of l-arabinose (39.78%) and d-galactose (40.59%) with minor amount of xylose, mannose and uronic acids. The maximum percent and the grafting efficiency of grafting acrylamide (AM) onto PG to form PG-AM were obtained by copolymerization between polysaccharide and 3 times (weight) acrylamide with 3 mmol/L potassium persulfate initiator at 50 °C for 1 h. In addition, lots of isolated and conjoint pores were observed in the prepared PG-AM materials, with a diameters distribution between 2 and 10 µm. Compared with PG, the synthesized copolymer PG-AM showed an excellent performance in thermal stability and swelling capacity. The detailed structural characteristic together with excellent thermal stability and swelling properties will benefit efficient utilization of the synthesized copolymer as a precursor for preparation of large-scale environmentally friendly advanced materials with various potential applications.


Assuntos
Gomas Vegetais/química , Polimerização , Polissacarídeos/química , Polissacarídeos/síntese química , Prunus domestica/química , Acrilamida/química , Técnicas de Química Sintética , Monossacarídeos/análise , Porosidade , Temperatura , Ácidos Urônicos/análise
9.
Adv Mater ; 31(26): e1806656, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31033052

RESUMO

Chemical synthesis is performed by reacting different chemical building blocks with defined stoichiometry, while meeting additional conditions, such as temperature and reaction time. Such a procedure is especially suited for automation and miniaturization. Life sciences lead the way to synthesizing millions of different oligonucleotides in extremely miniaturized reaction sites, e.g., pinpointing active genes in whole genomes, while chemistry advances different types of automation. Recent progress in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging could match miniaturized chemical synthesis with a powerful analytical tool to validate the outcome of many different synthesis pathways beyond applications in the life sciences. Thereby, due to the radical miniaturization of chemical synthesis, thousands of molecules can be synthesized. This in turn should allow ambitious research, e.g., finding novel synthesis routes or directly screening for photocatalysts. Herein, different technologies are discussed that might be involved in this endeavor. A special emphasis is given to the obstacles that need to be tackled when depositing tiny amounts of materials to many different extremely miniaturized reaction sites.


Assuntos
Materiais Biocompatíveis/síntese química , Miniaturização/métodos , Inteligência Artificial , Automação , DNA/síntese química , Microfluídica , Compostos Orgânicos/síntese química , Peptídeos/síntese química , Polissacarídeos/síntese química , Impressão Tridimensional , Proteínas/síntese química , Bibliotecas de Moléculas Pequenas/síntese química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
10.
Org Lett ; 21(7): 2374-2377, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30888190

RESUMO

The first synthesis of the hexasaccharide repeating unit of type VII group B Streptococcus capsular polysaccharide was achieved by a one-pot glycosylation strategy. The dimer of this repeating unit was also synthesized by one-pot glycosylation to achieve the backbone hexasaccharide first followed by one-pot dual glycosylations with the side-chain trisaccharide donor. All glycosylation reactions gave excellent stereoselectivity, which took advantage of a new stereospecific α-glucosylation method and the neighboring group participation effect for 1,2- trans glycosylations.


Assuntos
Streptococcus/química , Glicosilação , Estrutura Molecular , Polissacarídeos/síntese química , Polissacarídeos Bacterianos/síntese química , Trissacarídeos
11.
J Colloid Interface Sci ; 542: 253-262, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30763892

RESUMO

Polysaccharide is a renewable, biocompatible and biodegradable material that has received considerable attention. In this work, a series of polysaccharide gels were synthesized from the chemical cross-linking of pullulan with diglycerols. The effects of the diglycerol chain length on the performance of the gels were evaluated by XRD, TGA, SEM, rheological testings and swelling measurements. Overall, increasing the chain length resulted in a smaller pore size and stronger mechanical strength. Tetramethylene glycol diglycidyl ether (longest chain length)-derived Gel-T, which had the best performance (acceptable porous structure, good swelling ability and strong rigidity), was used to produce a nanocomposite hydrogel with montmorillonite (MMT). The incorporation of MMT led to a decrease in gel swelling and an increase in gel strength. The obtained nanocomposite system exhibited excellent adsorption properties (80 mg/g) towards crystal violet, and the adsorption behaviours were well represented by the pseudo-second-order kinetic and Langmuir isotherm models. Altogether, this study provides a better understanding of the structure-function relationships of pullulan-constructed hydrogel materials and will help to design more practical adsorbents for dye removal.


Assuntos
Glucanos/síntese química , Hidrogéis/síntese química , Nanocompostos/química , Polissacarídeos/síntese química , Águas Residuárias/química , Purificação da Água , Adsorção , Bentonita/química , Violeta Genciana/química , Glicerol/química , Cinética , Fenômenos Mecânicos , Porosidade , Poluentes Químicos da Água/química
12.
Int J Biol Macromol ; 123: 228-238, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30412755

RESUMO

A highly competent material, based on poly lactic acid (PLLA) grafted hydroxypropyl guar gum (HPG-g-PLLA) and polypyrrole/carboxylated multiwalled carbon nanotube (PPy/C-MWCNT) composite of various binary composition and copolymer of one of these nanocomposites have been synthesized successfully by in-situ polymerization. The environmentally affable nanocomposites have been characterized by spectroscopy, microscopy and thermogravimetry. Cytotoxicity of bio-nanocomposite has been inquired by cell viability study, which reveals its eco-friendly nature. The electrochemical properties of the biomaterials have been appraised by cyclic voltammetric studies. The PPy/C-MWCNT composite having 1 wt% C-MWCNT appears as the optimum composition from electrochemical studies. The hydrogel nanocomposite (HPG-g-PLLA5/0.5) copolymer behaves as a super ordinate material than pure PPy and PPy/C-MWCNT in every aspect of electrochemical properties like current density, stability, processibility and reversibility. Moreover the hydrogel nanocomposite, making electrode fabrication more simple and binder-free, nullifies all the interfacial complications arising from binders as well.


Assuntos
Biopolímeros/química , Nanotubos de Carbono/química , Poliésteres/síntese química , Polissacarídeos/síntese química , Galactanos/síntese química , Galactanos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Mananas/síntese química , Mananas/química , Nanocompostos/química , Gomas Vegetais/síntese química , Gomas Vegetais/química , Poliésteres/química , Polimerização , Polímeros/química , Polissacarídeos/química , Pirróis/química
13.
Carbohydr Polym ; 205: 83-88, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446152

RESUMO

Developing high-performance oxygen barrier films using biomass-based materials is crucial for the development of green and sustainable society. Herein, we develop a strategy to synthesize polyacrylic acid-grafted-acryloyl/hemicellulose composites (PAA-g-AH) as film materials with excellent oxygen barrier property. The as-synthesized films were extensively characterized by Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), gel permeation chromatography (GPC), 1H nuclear magnetic resonance (1H NMR), mechanical test, light transmittance and oxygen transmission rate (OTR) measurement. All these testing results showed that the optimum film exhibit great oxygen barrier property with a low OTR value of 0.25 ± 0.01 cm3* µm/(m2*d*kPa), which was much lower than that of pure PAA film. Moreover, the hybrid films possess well mechanical strength, light transmittance and recycle usage properties. Experimental results indicated that the as-synthesized films have great potential applications in several fields as packaging materials, such as drug, food and electronic products.


Assuntos
Resinas Acrílicas/química , Oxigênio/química , Polissacarídeos/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/efeitos da radiação , Embalagem de Alimentos/instrumentação , Resíduos Industriais , Luz , Polimerização , Polissacarídeos/síntese química , Polissacarídeos/isolamento & purificação , Polissacarídeos/efeitos da radiação , Reciclagem , Resistência à Tração , Água/química
14.
Chembiochem ; 20(7): 877-885, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30427113

RESUMO

The plant cell wall provides the richest available resource of fermentable carbohydrates and biobased materials. The main component of plant cell walls is cellulose, which is the most abundant biomolecule on earth. Apart from cellulose, which is constructed from relatively simple ß-1,4-glucan chains, plant cell walls also contain structurally more complex heteropolysaccharides (hemicellulose and pectin), as well as lignin and cell-wall proteins. A detailed understanding of the molecular structures, functions, and biosyntheses of cell-wall components is required to further promote their industrial use. Plant cell-wall research is, to a large degree, hampered by a lsack of available well-defined oligosaccharide samples that represent the structural features of cell-wall glycans. One technique to access these oligosaccharides is automated glycan assembly; a technique in which monosaccharide building blocks are, similarly to automated peptide and oligonucleotide chemistry, successively added to a linker-functionalized resin in a fully automated manner. Herein, recent research into the automated glycan assembly of different classes of cell-wall glycans used as molecular tools for cell-wall biology is discussed. More than 60 synthetic oligosaccharides were prepared and printed as microarrays for screening monoclonal antibodies that recognize plant cell-wall polysaccharides. The synthesized oligosaccharides have also been used to investigate glycosyltransferases and glycoside hydrolases, which are involved in synthesis and degradation of plant cell walls, as well as for the analysis of cell-wall-remodeling enzymes.


Assuntos
Parede Celular/metabolismo , Plantas/metabolismo , Polissacarídeos/metabolismo , Anticorpos Monoclonais/imunologia , Sequência de Carboidratos , Ensaios Enzimáticos , Glicosídeo Hidrolases/metabolismo , Glicosiltransferases/química , Glicosiltransferases/metabolismo , Polissacarídeos/síntese química , Polissacarídeos/imunologia , Especificidade por Substrato
15.
Int J Biol Macromol ; 124: 88-101, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439426

RESUMO

Biomimetic nanocomposites containing hydroxyapatite and natural polymers are promising candidates for bone grafting. In this work, a tricomponent bioactive nanocomposite (nHA-CH-TFSP) assembling nano-hydroxyapatite (nHA), Chitosan (CH) and Trigonella foenum graecum seed polysaccharide (TFSP) was developed using co-precipitation method and investigated against bicomponent nHA-CH nanocomposite for bone tissue engineering. In contrast to nHA-CH nanocomposite, nHA-CH-TFSP nanocomposite exhibited rough and interconnected porous structure as revealed by SEM with the porosity (60.3 ±â€¯0.17) lying in the range of cancellous bone. The incorporation of TFSP in nHA-CH substantially enhanced the in vitro water absorption capacity and protein adsorption ability along with appropriate biodegradation rate. Additionally, the nHA-CH-TFSP nanocomposite exhibited superior antibacterial activity. The nHA-CH-TFSP evinced a compressive strength of 6.7 ±â€¯0.24 MPa and a compressive modulus of 100 ±â€¯1.4 MPa, which fulfill the strength requisite of cancellous bone and could provide strong support for the growth of osteoblasts cells. Furthermore, the in vitro bioactivity study demonstrated its excellent biomineralization capacity in comparison to nHA-CH. The synthesized nHA-CH-TFSP nanocomposite exhibited better cytocompatibility towards the MG-63 cells along with its haemocompatible nature. Taken together the results of the present study indicate that nHA-CH-TFSP could serve as a prospective analogue for bone tissue engineering.


Assuntos
Materiais Biomiméticos/química , Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Polissacarídeos/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/farmacologia , Linhagem Celular , Quitosana/síntese química , Quitosana/farmacologia , Durapatita/síntese química , Durapatita/química , Durapatita/farmacologia , Humanos , Nanocompostos/química , Osteoblastos/efeitos dos fármacos , Polissacarídeos/síntese química , Polissacarídeos/farmacologia , Sementes/química , Engenharia Tecidual , Trigonella/química
16.
Carbohydr Polym ; 206: 163-173, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553309

RESUMO

Currently, selenium and polysaccharide combinations can be identified as three forms: natural selenium polysaccharides, synthetic selenium polysaccharides and selenium nanoparticles decorated with polysaccharides. Previous studies have indicated that these three combinations generally show better bioactivities, including immunomodulation, anti-tumour, antioxidation and glucose regulation, than those of either selenium or polysaccharides alone. Although they have not yet been developed as new drugs for clinical trials, results from previous studies have already shown their therapeutic potential for the future. In this article, we summarize our current state of understanding of the sources, preparation methods, physicochemical characteristics and bioactivities of these combinations for the discovery of novel therapeutic drugs and adjuvants.


Assuntos
Compostos Organosselênicos/uso terapêutico , Polissacarídeos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/síntese química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Bactérias/química , Linhagem Celular Tumoral , Fungos/química , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Fatores Imunológicos/síntese química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Nanopartículas/química , Neoplasias/tratamento farmacológico , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/isolamento & purificação , Compostos Organosselênicos/farmacologia , Plantas/química , Polissacarídeos/síntese química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Selênio/química
17.
Carbohydr Polym ; 206: 262-272, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553321

RESUMO

A rapid synthesis of the α(1→5) arabinofuranan polysaccharides, found on the outer surface of Mycobacterium tuberculosis (Mtb), is achieved by a regio- and stereocontrolled ring opening polymerization of ß-d-arabinofuranose-1,2,5-orthobenzoate. The robust polymerization reaction allows the incorporation of an amine linker, which was used to conjugate with protein tetanus toxoid (TT) to further investigate its adjuvant activities. The synthetic arabinan, which is the glycan on the non-reducing end of Mtb lipoarabinomannan (LAM), was evaluated for its immunological properties in vitro and in vivo. Systemic inflammation and the promotion of innate immune response were observed in macrophages treated with the synthetic arabinan as an adjuvant through an increase in the production of TNF-α and IL-12. In vivo evaluation of IFN-γ, IL-2, and TNF-α productions in mice pre-immunized with the synthetic arabinan conjugated TT indicated great enhancements of the immunological responses when compared to that of TT alone.


Assuntos
Adjuvantes Imunológicos/farmacologia , Glicoproteínas/imunologia , Polissacarídeos/imunologia , Toxoide Tetânico/imunologia , Adjuvantes Imunológicos/síntese química , Animais , Glicoproteínas/química , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/química , Polimerização , Polissacarídeos/síntese química , Polissacarídeos/farmacologia , Células RAW 264.7 , Estereoisomerismo , Toxoide Tetânico/química , Fator de Necrose Tumoral alfa/metabolismo
18.
Nat Commun ; 9(1): 5202, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30523255

RESUMO

The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.


Assuntos
Biologia Computacional/métodos , Oligossacarídeos/química , Oligossacarídeos/síntese química , Software , Sequência de Carboidratos , Modelos Químicos , Estrutura Molecular , Polissacarídeos/síntese química , Polissacarídeos/química , Reprodutibilidade dos Testes
19.
Proc Natl Acad Sci U S A ; 115(52): 13353-13358, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30530654

RESUMO

Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15- and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines.


Assuntos
Vacinas Bacterianas/imunologia , Polissacarídeos/imunologia , Streptococcus pneumoniae/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Glicoconjugados/imunologia , Infecções Pneumocócicas/imunologia , Polissacarídeos/síntese química , Coelhos , Sorogrupo , Vacinas Conjugadas/imunologia , Vacinas Sintéticas/imunologia
20.
Bioconjug Chem ; 29(11): 3847-3855, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30380836

RESUMO

The advancement of glycoscience is critically dependent on the access to a large number of glycans for their functional study. Naturally occurring glycans are considered a viable source for diverse and biologically relevant glycan libraries. A mixture of free reducing glycans released from natural sources can be fluorescently tagged and separated by chromatography to produce a natural glycan library. Anthranilic acid (AA) has been widely used to fluorescently tag reducing glycans for HPLC or LC/MS analysis. However, AA conjugated glycans are not efficiently immobilized on microarray slides due to the lack of a primary alkylamine functional group. In this study, we have developed simple and efficient chemistry for bioconjugation and further functionalization of glycan-AA conjugates. This new approach enables quick preparation of glycan microarrays and neoglycoproteins from glycan-AA conjugates, which can be separated by weak anion exchange (WAX) and C18 reversed-phase HPLC.


Assuntos
Corantes Fluorescentes/química , Glicômica/métodos , Polissacarídeos/química , ortoaminobenzoatos/química , Animais , Galinhas , Cromatografia Líquida de Alta Pressão/métodos , Corantes Fluorescentes/síntese química , Glicoproteínas/síntese química , Glicoproteínas/química , Análise em Microsséries , Polissacarídeos/análise , Polissacarídeos/síntese química , Espectrometria de Massas em Tandem/métodos , ortoaminobenzoatos/síntese química
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