Pub Date : 2024-09-24DOI: 10.1016/j.carres.2024.109282
Robert J. Nicholas, Nosa B. Idahagbon, Alexander Wei
Trifluoroacetic anhydride (TFAA) reacts smoothly with low molecular weight carbohydrates and cellulose nanofibers (CNFs) under base-free conditions. Methyl α- and β-d-glucopyranoside were used as model compounds to optimize reaction conditions, which were then applied to lyophilized CNFs for surface modification. ATR-IR spectroscopy and powder X-ray diffraction were employed to characterize the modified CNFs. Trifluoroacetylation for 4 h yields a degree of substitution (DS) of 0.4 acyl groups per anhydroglucose unit while maintaining a crystallinity index near 50 %. DS values were quantified by gravimetry, acid–base titration after saponification, and a novel approach utilizing solution 19F NMR spectroscopy which offers greater accuracy than the other techniques. This study presents an efficient, base-free method for derivatizing carbohydrates as well as surface functionalization of CNFs with trifluoroacetyl groups, potentially expanding their application in fiber-reinforced thermoplastic composites.
{"title":"Base-free trifluoroacetylation: From methyl glucopyranoside to cellulose nanofibers","authors":"Robert J. Nicholas, Nosa B. Idahagbon, Alexander Wei","doi":"10.1016/j.carres.2024.109282","DOIUrl":"10.1016/j.carres.2024.109282","url":null,"abstract":"<div><div>Trifluoroacetic anhydride (TFAA) reacts smoothly with low molecular weight carbohydrates and cellulose nanofibers (CNFs) under base-free conditions. Methyl α- and β-<span>d</span>-glucopyranoside were used as model compounds to optimize reaction conditions, which were then applied to lyophilized CNFs for surface modification. ATR-IR spectroscopy and powder X-ray diffraction were employed to characterize the modified CNFs. Trifluoroacetylation for 4 h yields a degree of substitution (DS) of 0.4 acyl groups per anhydroglucose unit while maintaining a crystallinity index near 50 %. DS values were quantified by gravimetry, acid–base titration after saponification, and a novel approach utilizing solution <sup>19</sup>F NMR spectroscopy which offers greater accuracy than the other techniques. This study presents an efficient, base-free method for derivatizing carbohydrates as well as surface functionalization of CNFs with trifluoroacetyl groups, potentially expanding their application in fiber-reinforced thermoplastic composites.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109282"},"PeriodicalIF":2.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1016/j.carres.2024.109281
Emmanilo Delar , Yanis Tigherghar , Laurie Girard , Mohamed Haddad , Charles Ramassamy , Jean Legault , Charles Gauthier
Phenylethanoid glycosides are a well-studied class of bioactive compounds found throughout the plant kingdom. In contrast, research on the synthesis and pharmacological activity of phenacyl glycosides, a specific subgroup of phenylethanoid glycosides with a ketone functionality at the alpha position of the phenol ring, has been limited. In this study, we report the synthesis, cytotoxic, antiviral, and anti-inflammatory evaluation of a series of 18 4′-hydroxyphenacyl glycosides. These compounds consist of six different sugar residues (β-d-glucose, β-d-galactose, α-l-arabinose, β-d-xylose, α-l-rhamnose, and β-d-glucuronic acid) and display three distinct methoxylation patterns at the phenacyl ring, similar to the substitution motifs of anthocyanins. We obtained the target phenacyl glycosides in high yield and stereoselectivity through the coupling of benzoyl-protected trichloroacetimidate glycosyl donors and corresponding acetophenones. Our work represents the first total synthesis of the natural products 4′-hydroxyphenacyl-β-d-glucopyranoside (1) and 4′-hydroxy-3′-methoxyphenacyl-β-d-glucopyranoside (2). None of the phenacyl glycosides showed cytotoxicity against the tested cell lines. Notably, several of the synthesized compounds exhibited antiviral activity, with natural product 2 being the most active against herpes simplex virus type 1, while phenacyl arabinoside 9 and natural product 2 were the most active against human coronavirus OC43. Natural product 2 significantly inhibited the production of interleukin-6 in lipopolysaccharide-stimulated microglia cells. Overall, our findings highlight the importance of the sugar residue and phenacyl ring substitution pattern in modulating the antiviral activity of phenacyl glycosides. Natural product 2 and phenacyl arabinoside 9 emerge as promising leads for the development of antiviral agents.
{"title":"Synthesis and pharmacological evaluation of nature-inspired phenacyl glycosides","authors":"Emmanilo Delar , Yanis Tigherghar , Laurie Girard , Mohamed Haddad , Charles Ramassamy , Jean Legault , Charles Gauthier","doi":"10.1016/j.carres.2024.109281","DOIUrl":"10.1016/j.carres.2024.109281","url":null,"abstract":"<div><div>Phenylethanoid glycosides are a well-studied class of bioactive compounds found throughout the plant kingdom. In contrast, research on the synthesis and pharmacological activity of phenacyl glycosides, a specific subgroup of phenylethanoid glycosides with a ketone functionality at the alpha position of the phenol ring, has been limited. In this study, we report the synthesis, cytotoxic, antiviral, and anti-inflammatory evaluation of a series of 18 4′-hydroxyphenacyl glycosides. These compounds consist of six different sugar residues (<em>β</em>-<span>d</span>-glucose, <em>β</em>-<span>d</span>-galactose, <em>α</em>-<span>l</span>-arabinose, <em>β</em>-<span>d</span>-xylose, <em>α</em>-<span>l</span>-rhamnose, and <em>β</em>-<span>d</span>-glucuronic acid) and display three distinct methoxylation patterns at the phenacyl ring, similar to the substitution motifs of anthocyanins. We obtained the target phenacyl glycosides in high yield and stereoselectivity through the coupling of benzoyl-protected trichloroacetimidate glycosyl donors and corresponding acetophenones. Our work represents the first total synthesis of the natural products 4′-hydroxyphenacyl-<em>β</em>-<span>d</span>-glucopyranoside (<strong>1</strong>) and 4′-hydroxy-3′-methoxyphenacyl-<em>β</em>-<span>d</span>-glucopyranoside (<strong>2</strong>). None of the phenacyl glycosides showed cytotoxicity against the tested cell lines. Notably, several of the synthesized compounds exhibited antiviral activity, with natural product <strong>2</strong> being the most active against herpes simplex virus type 1, while phenacyl arabinoside <strong>9</strong> and natural product <strong>2</strong> were the most active against human coronavirus OC43. Natural product <strong>2</strong> significantly inhibited the production of interleukin-6 in lipopolysaccharide-stimulated microglia cells. Overall, our findings highlight the importance of the sugar residue and phenacyl ring substitution pattern in modulating the antiviral activity of phenacyl glycosides. Natural product <strong>2</strong> and phenacyl arabinoside <strong>9</strong> emerge as promising leads for the development of antiviral agents.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109281"},"PeriodicalIF":2.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stereoselective synthesis of 2,3-diazido-2,3-dideoxy-β-d-mannosides has been accomplished via Cs2CO3-mediated anomeric O-alkylation of 2,3-diazido-2,3-dideoxy-β-d-mannoses with primary electrophiles. Selective oxidation of the C6 primary alcohol of the 2,3-diazido-2,3-dideoxy-β-d-mannoside successfully produced corresponding 2,3-diazido-2,3-dideoxy-β-d-mannuronic acid.
{"title":"Synthesis of 2,3-diazido-2,3-dideoxy-β-d-mannosides and 2,3-diazido-2,3-dideoxy-β-d-mannuronic acid via stereoselective anomeric O-alkylation","authors":"Rama Banjara, Prakash Thapa, Shailja Hitesh Kela, Fenglang Wu, Jianglong Zhu","doi":"10.1016/j.carres.2024.109279","DOIUrl":"10.1016/j.carres.2024.109279","url":null,"abstract":"<div><div>Stereoselective synthesis of 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannosides has been accomplished via Cs<sub>2</sub>CO<sub>3</sub>-mediated anomeric <em>O</em>-alkylation of 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannoses with primary electrophiles. Selective oxidation of the C6 primary alcohol of the 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannoside successfully produced corresponding 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannuronic acid.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109279"},"PeriodicalIF":2.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.carres.2024.109280
Louis J. Liotta, Jessica Antoine, Leighanne A. Brammer Basta, Andrew S. Campbell, Gabrielle Y. Cole, Kristen A. Demick Brazile, Natalie M. Dogal Gardner, Megan E. Fitzgerald, Jean E.K. Francois, Brian M. French, Sara L. Garafola, Catherine A. Giannetti, Eve A. Granatosky, Alycen M. Harney, James T. Hummel, Andrew P. Joyce, Mitchell H. Keylor, Jasmine A. Khubchandani, Claudia Korzeniecki, Diana C. Lieberman, Kerstin L. Tougas
Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) 1b, lentiginosine 3a, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 with yields ranging from 38 % to 68 % for the DAB and isomers 1a-1h and from 44 % to 89 % for the lentiginosine and isomers 3a-3h. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars.
{"title":"Efficient synthesis for each of the eight stereoisomers of the iminosugars lentiginosine and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB)","authors":"Louis J. Liotta, Jessica Antoine, Leighanne A. Brammer Basta, Andrew S. Campbell, Gabrielle Y. Cole, Kristen A. Demick Brazile, Natalie M. Dogal Gardner, Megan E. Fitzgerald, Jean E.K. Francois, Brian M. French, Sara L. Garafola, Catherine A. Giannetti, Eve A. Granatosky, Alycen M. Harney, James T. Hummel, Andrew P. Joyce, Mitchell H. Keylor, Jasmine A. Khubchandani, Claudia Korzeniecki, Diana C. Lieberman, Kerstin L. Tougas","doi":"10.1016/j.carres.2024.109280","DOIUrl":"10.1016/j.carres.2024.109280","url":null,"abstract":"<div><div>Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) <strong>1b</strong>, lentiginosine <strong>3a</strong>, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides <strong>47</strong> with yields ranging from 38 % to 68 % for the DAB and isomers <strong>1a-1h</strong> and from 44 % to 89 % for the lentiginosine and isomers <strong>3a-3h</strong>. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides <strong>47</strong> from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides <strong>47</strong> to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109280"},"PeriodicalIF":2.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1016/j.carres.2024.109278
Lorena Herrera , María Eugenia Cedrés , Paula Rodríguez Bonnecarrere , Cecilia Giacomini
Biological glycans mediate several physiological processes, thus altered glycosylation patterns can lead to different diseases such as autoimmune, infectious, chronic anti-inflammatory diseases, or even cancer. In fact, alterations in fucosylation in either N- or O-glycans are among the most frequent changes in glycosylation patterns associated with cancer. Therefore, elucidation of the role of glycoconjugate glycans is essential for understanding the development of pathologies where they are involved. In this sense glycosidases are excellent tools, since they catalyse the selective removal of sugar residues, allowing the evaluation of changes in their biological role due to glycan removal. This work describes the purification and characterization of a α-fucosidase from the fungus Dichostereum sordulentum 1488. It is a homodimer with a molecular weight of 214 kDa and optimum pH and temperature of 4.0 and 70 °C respectively. It has a KM of 0.27 mM and VMax of 3.3 μmoles PNP/min per mg for the substrate p-nitrophenyl-α-l-fucopyranoside, showing a substrate inhibition profile. It showed high specificity for the hydrolysis of fucose linked by α-(1,2) bonds. The identification, purification, and characterization of this new α-fucosidase is highly relevant for enlarging the availability of glycosidases for use as tools for glycan elucidation.
{"title":"Purification and characterization of α-fucosidase from Dichostereum sordulentum 1488","authors":"Lorena Herrera , María Eugenia Cedrés , Paula Rodríguez Bonnecarrere , Cecilia Giacomini","doi":"10.1016/j.carres.2024.109278","DOIUrl":"10.1016/j.carres.2024.109278","url":null,"abstract":"<div><div>Biological glycans mediate several physiological processes, thus altered glycosylation patterns can lead to different diseases such as autoimmune, infectious, chronic anti-inflammatory diseases, or even cancer. In fact, alterations in fucosylation in either N- or <em>O</em>-glycans are among the most frequent changes in glycosylation patterns associated with cancer. Therefore, elucidation of the role of glycoconjugate glycans is essential for understanding the development of pathologies where they are involved. In this sense glycosidases are excellent tools, since they catalyse the selective removal of sugar residues, allowing the evaluation of changes in their biological role due to glycan removal. This work describes the purification and characterization of a α-fucosidase from the fungus <em>Dichostereum sordulentum</em> 1488. It is a homodimer with a molecular weight of 214 kDa and optimum pH and temperature of 4.0 and 70 °C respectively. It has a K<sub>M</sub> of 0.27 mM and V<sub>Max</sub> of 3.3 μmoles PNP/min per mg for the substrate <em>p</em>-nitrophenyl-α-<span>l</span>-fucopyranoside, showing a substrate inhibition profile. It showed high specificity for the hydrolysis of fucose linked by α-(1,2) bonds. The identification, purification, and characterization of this new α-fucosidase is highly relevant for enlarging the availability of glycosidases for use as tools for glycan elucidation.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109278"},"PeriodicalIF":2.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1016/j.carres.2024.109273
Nikolay P. Arbatsky , Alexander S. Shashkov , Mikhail M. Shneider , Yulia V. Mikhailova , Andrey A. Shelenkov , Eugene A. Sheck , Anastasia A. Kasimova , Nadezhda A. Kalinchuk , Johanna J. Kenyon , Yuriy A. Knirel
Capsular polysaccharide (CPS) is a heteroglycan that coats the cell surface of most isolates of the important Gram-negative bacterial pathogen, Acinetobacter baumannii. Strain MAR 15–4076, a clinical isolate recovered in Russia in 2015, was found to carry the KL129 sequence at the CPS biosynthesis K locus. The CPS was isolated from the strain and studied by sugar analysis, Smith degradation, one- and two-dimensional 1H and 13C NMR spectroscopy. It was composed of branched pentasaccharide units that include a →3)-α-l-Rhap-(1 → 3)-α-l-Rhap-(1 → 3)-β-d-GlcpNAc-(1→ mainchain and α-d-ManpNAc-(1 → 3)-l-Rhap side branch. Though the pentasaccharide units are identical to those that make up the K84 CPS produced by A. baumannii LUH5540, the units are linked differently via the substitution of an alternate l-Rhap residue, resulting in a difference in the overall topology of the CPS. This was due to the replacement of the Wzy polymerase gene encoded at the K locus.
{"title":"The K129 capsular polysaccharide produced by Acinetobacter baumannii MAR 15–4076 has the same composition as K84 but differs in the linkage between units altering the overall branching topology","authors":"Nikolay P. Arbatsky , Alexander S. Shashkov , Mikhail M. Shneider , Yulia V. Mikhailova , Andrey A. Shelenkov , Eugene A. Sheck , Anastasia A. Kasimova , Nadezhda A. Kalinchuk , Johanna J. Kenyon , Yuriy A. Knirel","doi":"10.1016/j.carres.2024.109273","DOIUrl":"10.1016/j.carres.2024.109273","url":null,"abstract":"<div><div>Capsular polysaccharide (CPS) is a heteroglycan that coats the cell surface of most isolates of the important Gram-negative bacterial pathogen, <em>Acinetobacter baumannii.</em> Strain MAR 15–4076, a clinical isolate recovered in Russia in 2015, was found to carry the KL129 sequence at the CPS biosynthesis K locus. The CPS was isolated from the strain and studied by sugar analysis, Smith degradation, one- and two-dimensional <sup>1</sup>H and <sup>13</sup>C NMR spectroscopy. It was composed of branched pentasaccharide units that include a →3)-α-<span>l</span>-Rha<em>p</em>-(1 → 3)-α-<span>l</span>-Rha<em>p</em>-(1 → 3)-β-<span>d</span>-Glc<em>p</em>NAc-(1→ mainchain and α-<span>d</span>-Man<em>p</em>NAc-(1 → 3)-<span>l</span>-Rha<em>p</em> side branch. Though the pentasaccharide units are identical to those that make up the K84 CPS produced by <em>A. baumannii</em> LUH5540, the units are linked differently via the substitution of an alternate <span>l</span>-Rha<em>p</em> residue, resulting in a difference in the overall topology of the CPS. This was due to the replacement of the Wzy polymerase gene encoded at the K locus.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109273"},"PeriodicalIF":2.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.carres.2024.109277
Inesa V. Blagodatskikh , Oxana V. Vyshivannaya , Nikita A. Tishchenko , Evgeniya A. Bezrodnykh , Vladimir E. Piskarev , Rinat R. Aysin , Yurij A. Antonov , Victor N. Orlov , Vladimir E. Tikhonov
Interaction of chitosan and its derivatives with proteins of animal blood at blood pH relevant conditions is of a particular interest for construction of antimicrobial chitosan/protein-based drug delivery systems. In this work, the interaction of a series of N-reacetylated oligochitosans (RA-CHI) having Mw of 10–12 kDa and differing in the degree of acetylation (DA 19, 24, and 40 %) with bovine serum albumin (BSA) in alkalescent media is described in first. It is shown that RA-CHI forms soluble complexes with BSA in solutions with pH 7.4 and a low ionic strength. Light scattering study shows that soluble RA-CHI complexes have spherical form with the radius of about 100 nm. Circular dichroism, fluorescent spectroscopy, and micro-IR spectroscopy studies show that the secondary structure of BSA in soluble complexes remain intact. Isothermal titration calorimetry of RA-CHI with DA 24 % and BSA mixing in the buffers with different ionization heats reveals a significant contribution of electrostatic forces to the binding process and an additional ionization of chitosan due to the proton transfer from the buffer substance. An increase of ionic strength to the blood relevant value 0.15 M suppresses the binding. It is shown that application of RA-CHI with higher DA value leads to a decrease in the affinity of RA-CHI to BSA and an alteration of the interaction mechanism. The finding opens an opportunity to the application of N-reacetylated chitosan derivatives in the complex systems compatible with blood plasma proteins.
{"title":"Interaction between reacetylated chitosan and albumin in alcalescent media","authors":"Inesa V. Blagodatskikh , Oxana V. Vyshivannaya , Nikita A. Tishchenko , Evgeniya A. Bezrodnykh , Vladimir E. Piskarev , Rinat R. Aysin , Yurij A. Antonov , Victor N. Orlov , Vladimir E. Tikhonov","doi":"10.1016/j.carres.2024.109277","DOIUrl":"10.1016/j.carres.2024.109277","url":null,"abstract":"<div><p>Interaction of chitosan and its derivatives with proteins of animal blood at blood pH relevant conditions is of a particular interest for construction of antimicrobial chitosan/protein-based drug delivery systems. In this work, the interaction of a series of <em>N</em>-reacetylated oligochitosans (RA-CHI) having <em>M</em><sub><em>w</em></sub> of 10–12 kDa and differing in the degree of acetylation (DA 19, 24, and 40 %) with bovine serum albumin (BSA) in alkalescent media is described in first. It is shown that RA-CHI forms soluble complexes with BSA in solutions with pH 7.4 and a low ionic strength. Light scattering study shows that soluble RA-CHI complexes have spherical form with the radius of about 100 nm. Circular dichroism, fluorescent spectroscopy, and micro-IR spectroscopy studies show that the secondary structure of BSA in soluble complexes remain intact. Isothermal titration calorimetry of RA-CHI with DA 24 % and BSA mixing in the buffers with different ionization heats reveals a significant contribution of electrostatic forces to the binding process and an additional ionization of chitosan due to the proton transfer from the buffer substance. An increase of ionic strength to the blood relevant value 0.15 M suppresses the binding. It is shown that application of RA-CHI with higher DA value leads to a decrease in the affinity of RA-CHI to BSA and an alteration of the interaction mechanism. The finding opens an opportunity to the application of N-reacetylated chitosan derivatives in the complex systems compatible with blood plasma proteins.</p></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109277"},"PeriodicalIF":2.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.carres.2024.109276
Karl Martin Ingerma , Indrek Reile , Rando Tuvikene
Alginates are brown algal polysaccharides consisting of β-D-mannuronic (M) and α-l-guluronic acid (G) residues linked with 1→4 glycosidic bonds. To functionalize these natural resources for biomedical use, alginates can be chemically modified, including by sulfation. Here regioselective sulfation of alginates at M-2 in DMSO with Py∙SO3 is described, by either sulfating alginates directly or through using alginates with added protecting groups (PG-s), including TBDMS-ether, Piv-, Bz-esters and intramolecular 3,6-lactone. Highest regioselectivity was found by sulfating TBDMS- and Piv-protected alginates, with over 65 % of M-residues being 2-O-sulfated. However significant reduction in molecular weight was found when alginates were sulfated in DMSO. Results from this work will allow a degree of control over substitution patterns in sulfated alginates. This will allow to more accurately determine structure-property relationships in biomedical research.
{"title":"Regioselective sulfation of alginate at 2-O-position of mannuronic acid unit with Py∙SO3 in DMSO","authors":"Karl Martin Ingerma , Indrek Reile , Rando Tuvikene","doi":"10.1016/j.carres.2024.109276","DOIUrl":"10.1016/j.carres.2024.109276","url":null,"abstract":"<div><p>Alginates are brown algal polysaccharides consisting of β-D-mannuronic (M) and α-<span>l</span>-guluronic acid (G) residues linked with 1→4 glycosidic bonds. To functionalize these natural resources for biomedical use, alginates can be chemically modified, including by sulfation. Here regioselective sulfation of alginates at M-2 in DMSO with Py∙SO<sub>3</sub> is described, by either sulfating alginates directly or through using alginates with added protecting groups (PG-s), including TBDMS-ether, Piv-, Bz-esters and intramolecular 3,6-lactone. Highest regioselectivity was found by sulfating TBDMS- and Piv-protected alginates, with over 65 % of M-residues being 2-<em>O</em>-sulfated. However significant reduction in molecular weight was found when alginates were sulfated in DMSO. Results from this work will allow a degree of control over substitution patterns in sulfated alginates. This will allow to more accurately determine structure-property relationships in biomedical research.</p></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109276"},"PeriodicalIF":2.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1016/j.carres.2024.109275
Sean T. Evans , Graham J. Tizzard , Robert A. Field , Gavin J. Miller
Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-d-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-d-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d-glucoside with TBAF. Unexpectedly, an anomeric pyridinium salt was isolated when attempting to form the C2-triflate using Tf2O in pyridine. Indicatively, this proceeds via a 1 → 2 S-migration delivering a 1,2-trans product with α-d-manno configuration and the anomeric pyridinium in a pseudo-equatorial position. The structure of this unexpected intermediate was confirmed in the solid-state using X-ray crystallography. Omission of the pyridine solvent led to dimer formation. Switching the aglycone to an O-para-methoxyphenyl enabled smooth C2 inversion to the desired 2-deoxy-2-fluoro d-mannose system, suitably equipped for further anomeric manipulation.
{"title":"Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration","authors":"Sean T. Evans , Graham J. Tizzard , Robert A. Field , Gavin J. Miller","doi":"10.1016/j.carres.2024.109275","DOIUrl":"10.1016/j.carres.2024.109275","url":null,"abstract":"<div><div>Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-<span>d</span>-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion <em>via</em> a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-<span>d</span>-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding <span>d</span>-glucoside with TBAF. Unexpectedly, an anomeric pyridinium salt was isolated when attempting to form the C2-triflate using Tf<sub>2</sub>O in pyridine. Indicatively, this proceeds <em>via</em> a 1 → 2 <em>S</em>-migration delivering a 1,2-<em>trans</em> product with α-<span>d</span>-manno configuration and the anomeric pyridinium in a pseudo-equatorial position. The structure of this unexpected intermediate was confirmed in the solid-state using X-ray crystallography. Omission of the pyridine solvent led to dimer formation. Switching the aglycone to an <em>O</em>-<em>para</em>-methoxyphenyl enabled smooth C2 inversion to the desired 2-deoxy-2-fluoro <span>d</span>-mannose system, suitably equipped for further anomeric manipulation.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109275"},"PeriodicalIF":2.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1016/j.carres.2024.109274
Vinh Nghi Nguyen , Van Bon Nguyen , Minh Dinh Tran , Manh Dung Doan , Dinh Sy Nguyen , Thi Huyen Nguyen , Chien Thang Doan , Thi Ngoc Tran , San Lang Wang , Anh Dzung Nguyen
Ampicillin (Amp), an antibiotic, is widely used to treat bacterial infections in humans and livestock, but recently the rate of resistance has increased rapidly. The aim of this work was to enhancing the antibacterial effect of this compound against AMR Staphylococcus aureus via loading Amp into chitosan/starch nanocomposites by spray drying technique. The results showed that the different ratio of chitosan gel and starch gel used in preparing the nanocomposites can affect its properties and performance. The size distribution of the nanocomposite particles was ranging from 122.0 to 816.9 nm. The zeta potential values of the nanocomposites range from +29.47 to +93.07 mV, indicating the stability of the particles and their tendency to repel each other. Ampicillin was loaded into the chitosan/starch nanocomposites with encapsulation efficiency of 70.7–77.3 %, then their releasing and antibacterial effect against AMR S. aureus were investigated. The results indicated that antibacterial activity of chitosan/starch nanocomposites loaded ampicillin was much higher than ampicillin alone. Chitosan/starch nanocomposites loaded ampicillin at concentration 5.0 μg/mL inhibited 88.6 % growth of S. aureus to a similar extent as 7.5 μg/mL of ampicillin alone. Additionally, at same 7.5 μg/mL ampicillin concentration, the nanocomposites loaded ampicillin showed a higher inhibitory rate (93.27 %) compared to ampicillin alone (88.96 %) over a 12 h-period. Especially, the antibacterial activity of chitosan/starch nanocomposites loaded ampicillin still maintained their effectiveness over 48 h (95.43 %) while those the ampicillin decreased down to 85.76 %. This research highlights the potential of using the chitosan/starch nanocomposites as nanocarriers for ampicillin to enhance its antibacterial activity against AMR Staphylococcus aureus. This approach could be a promising strategy to combat antimicrobial resistance.
{"title":"Enhancing the antibacterial activity of ampicillin loaded into chitosan/starch nanocomposites against AMR Staphylococcus aureus","authors":"Vinh Nghi Nguyen , Van Bon Nguyen , Minh Dinh Tran , Manh Dung Doan , Dinh Sy Nguyen , Thi Huyen Nguyen , Chien Thang Doan , Thi Ngoc Tran , San Lang Wang , Anh Dzung Nguyen","doi":"10.1016/j.carres.2024.109274","DOIUrl":"10.1016/j.carres.2024.109274","url":null,"abstract":"<div><p>Ampicillin (Amp), an antibiotic, is widely used to treat bacterial infections in humans and livestock, but recently the rate of resistance has increased rapidly. The aim of this work was to enhancing the antibacterial effect of this compound against <em>AMR Staphylococcus aureus</em> via loading Amp into chitosan/starch nanocomposites by spray drying technique. The results showed that the different ratio of chitosan gel and starch gel used in preparing the nanocomposites can affect its properties and performance. The size distribution of the nanocomposite particles was ranging from 122.0 to 816.9 nm. The zeta potential values of the nanocomposites range from +29.47 to +93.07 mV, indicating the stability of the particles and their tendency to repel each other. Ampicillin was loaded into the chitosan/starch nanocomposites with encapsulation efficiency of 70.7–77.3 %, then their releasing and antibacterial effect against AMR <em>S. aureus</em> were investigated. The results indicated that antibacterial activity of chitosan/starch nanocomposites loaded ampicillin was much higher than ampicillin alone. Chitosan/starch nanocomposites loaded ampicillin at concentration 5.0 μg/mL inhibited 88.6 % growth of <em>S. aureus</em> to a similar extent as 7.5 μg/mL of ampicillin alone. Additionally, at same 7.5 μg/mL ampicillin concentration, the nanocomposites loaded ampicillin showed a higher inhibitory rate (93.27 %) compared to ampicillin alone (88.96 %) over a 12 h-period. Especially, the antibacterial activity of chitosan/starch nanocomposites loaded ampicillin still maintained their effectiveness over 48 h (95.43 %) while those the ampicillin decreased down to 85.76 %. This research highlights the potential of using the chitosan/starch nanocomposites as nanocarriers for ampicillin to enhance its antibacterial activity against AMR <em>Staphylococcus aureus.</em> This approach could be a promising strategy to combat antimicrobial resistance.</p></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109274"},"PeriodicalIF":2.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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