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Biomedicine & Pharmacotherapy =... Oct 2023Long-acting and specific targeting are two important properties of excellent drug delivery systems. Currently, the long-acting strategies based on polyethylene glycol... (Review)
Review
Long-acting and specific targeting are two important properties of excellent drug delivery systems. Currently, the long-acting strategies based on polyethylene glycol (PEG) are controversial, and PEGylation is incapable of simultaneously possessing targeting ability. Thus, it is crucial to identify and develop approaches to produce long-acting and targeted drug delivery systems. Sialic acid (SA) is an endogenous, negatively charged, nine-carbon monosaccharide. SA not only mediates immune escape in the body but also binds to numerous disease related targets. This suggests a potential strategy, namely "sialylation," for preparing long-acting and targeted drug delivery systems. This review focuses on the application status of SA-based long-acting and targeted agents as a reference for subsequent research.
Topics: Carbon; Drug Delivery Systems; Monosaccharides; N-Acetylneuraminic Acid; Polyethylene Glycols
PubMed: 37611437
DOI: 10.1016/j.biopha.2023.115353 -
Chemical Reviews Oct 2022Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications... (Review)
Review
Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications involving polyfluorinated carbohydrates, here defined as monosaccharides in which more than one carbon has at least one fluorine substituent directly attached to it, with the notable exception of their use as mechanism-based inhibitors. The increasing attention to carbohydrate physical properties, especially around lipophilicity, has resulted in a surge of interest for this class of compounds. This review covers the considerable body of work toward the synthesis of polyfluorinated hexoses, pentoses, ketosugars, and aminosugars including sialic acids and nucleosides. An overview of the current state of the art of their glycosidation is also provided.
Topics: Fluorine; Carbohydrates; Hexoses; Pentoses; Monosaccharides; Nucleosides; Sialic Acids; Carbon
PubMed: 35613331
DOI: 10.1021/acs.chemrev.2c00086 -
Journal of Inherited Metabolic Disease Jul 2021
Topics: Acetylgalactosamine; Homocysteine; Humans; Porphyria, Acute Intermittent; Pyrrolidines
PubMed: 34145602
DOI: 10.1002/jimd.12411 -
Journal of the American Board of Family... 2020This issue of the contains some exceptional research articles. A few are truly "must-reads," including a fascinating look at the relationship between having a usual...
This issue of the contains some exceptional research articles. A few are truly "must-reads," including a fascinating look at the relationship between having a usual source of care and telomere length. Glucosamine/chrondroitin supplementation seems to be helpful for more than just arthritis pain. There is a very practical advice on keeping patients discharged from the emergency department out of the hospital and on reducing patient requests for inappropriate antibiotics. This issue also features 5 articles addressing how family physicians can combat the opioid epidemic. Three articles highlight research on diabetes and another 3 on breast cancer. Payment reform, dermoscopy, and telemedicine are among many other topics covered.
Topics: Analgesics, Opioid; Chondroitin; Dietary Supplements; Family Practice; Glucosamine; Humans; Physician-Patient Relations; Telomere
PubMed: 33219058
DOI: 10.3122/jabfm.2020.06.200513 -
Yakugaku Zasshi : Journal of the... 2023Boronic acids are able to reversibly interact with the diol groups, a commonly found motif in biomolecules including sugars, ribose and catechols. For their...
Boronic acids are able to reversibly interact with the diol groups, a commonly found motif in biomolecules including sugars, ribose and catechols. For their carbohydrate-binding properties, they can be regarded as a synthetic mimic of lectins and often termed as "borono-lectins." Importantly, the borono-lectins platform can be chemically tailored to manifest a broad profile of binding strength and specificity. Besides the structural versatility, some derivatives can undergo a sharp inversion in the state of hydration in synchronization with the molecular recognitions. This feature, when combined with amphiphilic polymeric backbones, translates into many creative principles for fine-tuning or switching the hydration and more complex molecular assemblies in a way interactive with biology. Here we provide a brief overview of our recent efforts on the related applications with special focuses on smart insulin delivery systems and sialic acid detections relevant to cancer diagnosis and treatment among others.
Topics: Lectins; N-Acetylneuraminic Acid; Bioengineering
PubMed: 37121759
DOI: 10.1248/yakushi.22-00205-3 -
Nature Communications Dec 2023Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus...
Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus with sialic acid is poorly characterized. Using S. aureus USA300 as well as clinical isolates, we demonstrate that quorum-sensing dysfunction, a hallmark of S. aureus adaptation, correlates with a greater ability to consume free sialic acid, providing a growth advantage in an air-liquid interface model and in vivo. Furthermore, RNA-seq experiment reveals that free sialic acid triggers transcriptional reprogramming promoting S. aureus chronic lifestyle. To support the clinical relevance of our results, we show the co-occurrence of S. aureus, sialidase-producing microbiota and free sialic acid in the airway of patients with cystic fibrosis. Our findings suggest a dual role for sialic acid in S. aureus airway infection, triggering virulence reprogramming and driving S. aureus adaptive strategies through the selection of quorum-sensing dysfunctional strains.
Topics: Humans; Staphylococcus aureus; Quorum Sensing; N-Acetylneuraminic Acid; Respiratory System; Staphylococcal Infections; Bacterial Proteins
PubMed: 38065959
DOI: 10.1038/s41467-023-43863-2 -
Protein & Cell May 2023
Topics: Oxidative Phosphorylation; Acetylglucosamine; Uridine Diphosphate N-Acetylglucosamine
PubMed: 37155316
DOI: 10.1093/procel/pwac009 -
Biotechnology Advances Nov 2020Sialic acids are important recognition sites in protein- and lipid-linked glycans of higher organisms and of select bacteria and protozoa. They are also prominent in... (Review)
Review
Sialic acids are important recognition sites in protein- and lipid-linked glycans of higher organisms and of select bacteria and protozoa. They are also prominent in human milk oligosaccharides. Defined sialo-oligosaccharides have interesting applications in chemical glycobiology and represent emerging ingredients for health-related nutrition. The growing demand for sialo-oligosaccharides has promoted developments in multidisciplinary carbohydrate synthesis, with approaches by cascade bio-catalysis having a leading role. The key synthetic step involves catalysis by sialyltransferases (EC 2.4.99.-) and consists in attaching sialic acid from a cytidine 5'-monophosphate-activated donor (CMP-sialic acid) to the nascent oligosaccharide acceptor. Sialyltransferases from bacteria, in general, show convenient properties for application (e.g., relative ease of recombinant production; high specific activity and operational stability). Here, we review salient characteristics of the bacterial sialyltransferases active on d-galactose- and N-acetyl-d-galactosamine-containing acceptors and highlight advances of their development into efficient biocatalysts. We also show integration of these sialyltransferases into multistep enzymatic cascades for sialo-oligosaccharide (e.g., sialyllactose) production from expedient substrates, using in situ formation of the CMP-sialic acid donor. We summarize functional parameters of the enzymes for CMP-sialic acid supply and analyze multi-enzymatic synthesis of sialo-oligosaccharides from a reaction engineering point of view. We discuss opportunities of sialyltransferase cascades for efficient sialo-oligosaccharide production in vitro and in vivo.
Topics: Bacteria; Humans; N-Acetylneuraminic Acid; Oligosaccharides; Polysaccharides; Sialyltransferases
PubMed: 32822768
DOI: 10.1016/j.biotechadv.2020.107613 -
NPJ Biofilms and Microbiomes Jun 2023Dietary fiber consumption has been linked with improved cardiometabolic health, however, human studies have reported large interindividual variations in the observed...
Dietary fiber consumption has been linked with improved cardiometabolic health, however, human studies have reported large interindividual variations in the observed benefits. We tested whether the effects of dietary fiber on atherosclerosis are influenced by the gut microbiome. We colonized germ-free ApoE mice with fecal samples from three human donors (DonA, DonB, and DonC) and fed them diets supplemented with either a mix of 5 fermentable fibers (FF) or non-fermentable cellulose control (CC) diet. We found that DonA-colonized mice had reduced atherosclerosis burden with FF feeding compared to their CC-fed counterparts, whereas the type of fiber did not affect atherosclerosis in mice colonized with microbiota from the other donors. Microbial shifts associated with FF feeding in DonA mice were characterized by higher relative abundances of butyrate-producing taxa, higher butyrate levels, and enrichment of genes involved in synthesis of B vitamins. Our results suggest that atheroprotection in response to FF is not universal and is influenced by the gut microbiome.
Topics: Humans; Animals; Mice; Dietary Fiber; Microbiota; Cellulose; Butyrates; Glucosamine; Atherosclerosis
PubMed: 37270570
DOI: 10.1038/s41522-023-00402-7 -
ACS Chemical Biology Mar 2023Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from...
Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from sialosides, and their inhibition is a prime target for viral infection treatment. The connectivity and type of sialic acid influence the recognition and hydrolysis activity of the many different neuraminidases. The common strategies to evaluate neuraminidase activity, recognition, and inhibition rely on extensive labeling and require a large amount of sialylated glycans. The above limitations make the effort of finding viral inhibitors extremely difficult. We used synthetic sialylated glycans and developed a label-free electrochemical method to show that sialoside structural features lead to selective neuraminidase biosensing. We compared Neu5Ac to Neu5Gc sialosides to evaluate the organism-dependent neuraminidase selectivity-sensitivity relationship. We demonstrated that the type of surface and the glycan monolayer density direct the response to either binding or enzymatic activity. We proved that while the hydrophobic glassy carbon surface increases the interaction with the enzyme hydrophobic interface, the negatively charged interface of the lipoic acid monolayer on gold repels the protein and enables biocatalysis. We showed that the sialoside monolayers can serve as tools to evaluate the inhibition of neuraminidases both by biocatalysis and molecular recognition.
Topics: Neuraminidase; N-Acetylneuraminic Acid; Biocatalysis; Sialic Acids; Polysaccharides
PubMed: 36792550
DOI: 10.1021/acschembio.2c00913