51236-40-9Relevant articles and documents
Synthesis of Asparagine Derivatives Harboring a Lewis X Type DC-SIGN Ligand and Evaluation of their Impact on Immunomodulation in Multiple Sclerosis
Doelman, Ward,Marqvorsen, Mikkel H. S.,Chiodo, Fabrizio,Bruijns, Sven C. M.,van der Marel, Gijsbert A.,van Kooyk, Yvette,van Kasteren, Sander I.,Araman, Can
supporting information, p. 2742 - 2752 (2020/12/29)
The protein myelin oligodendrocyte glycoprotein (MOG) is a key component of myelin and an autoantigen in the disease multiple sclerosis (MS). Post-translational N-glycosylation of Asn31 of MOG seems to play a key role in modulating the immune response towards myelin. This is mediated by the interaction of Lewis-type glycan structures in the N-glycan of MOG with the DC-SIGN receptor on dendritic cells (DCs). Here, we report the synthesis of an unnatural Lewis X (LeX)-containing Fmoc-SPPS-compatible asparagine building block (SPPS=solid-phase peptide synthesis), as well as asparagine building blocks containing two LeX-derived oligosaccharides: LacNAc and Fucα1-3GlcNAc. These building blocks were used for the glycosylation of the immunodominant portion of MOG (MOG31-55) and analyzed with respect to their ability to bind to DC-SIGN in different biological setups, as well as their ability to inhibit the citrullination-induced aggregation of MOG31-55. Finally, a cytokine secretion assay was carried out on human monocyte-derived DCs, which showed the ability of the neoglycopeptide decorated with a single LeX to alter the balance of pro- and anti-inflammatory cytokines, inducing a tolerogenic response.
NOVEL IMMUNODULATING SMALL MOLECULES
-
Paragraph 0186, (2020/01/31)
The present invention includes novel compositions and methods for treating comprising a compound with the Formula I: where n = 0-5; X = NH, O, S, CH2; Y = Phenyl, a phenyl group substituted with at least one methyl, a phenyl group substituted with at least one nitro, a phenyl group substituted with at least one nitrogen, a phenyl group substituted with at least one boron, aryl, substituted aryl, heteroaryl, four to six membered cycloalkyl, four to six membered heterocycloalkyl; R = H, C(O)R2, SO2R2; R1 = H, C(O)R2, SO2R2; R2 = Ethyl, methyl, isopropyl, n-propyl, t-butyl, n- butyl, NH2, NR3R4; R3, R4 = Ethyl, methyl, isopropyl, n-propyl, t-butyl, n-butyl, three to six membered cycloalkyl and Z = NH, O, S, CH2 or none, wherein the amount of the compound is selected to either inhibit or activate the immune response.
DRUG DELIVERY
-
Page/Page column 22, (2019/11/19)
A drug delivery vehicle comprising a vesicle conjugated to one or more targeting groups, wherein the targeting groups comprise an oligosaccharide which is Lewis A or Lewis B or a mimetic thereof, or a pharmaceutically acceptable salt or PEGylated form of the oligosaccharide : (I) wherein R represents the pointof attachment to the vesicle.10
Synthesis and biological evaluation of novel C1-glycosyl thiazole derivatives as acetylcholinesterase inhibitors
Yin, Long,Cheng, Feng-Chang,Li, Qu-Xiang,Liu, Wei-Wei,Liu, Xiu-Jian,Cao, Zhi-Ling,Shi, Da-Hua
, p. 545 - 548 (2016/10/05)
A new series of C1-glycosyl thiazole derivatives was synthesised by the reaction of 1-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)thiourea with 2-bromoacetophenone derivatives. Subsequent removal of the acetyl groups were conducted using NaOMe-MeOH. The structures of all new products were confirmed by IR, 1H NMR and HRMS (ESI). The acetylcholinesterase inhibitory activities of these new compounds were tested. Among them, N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(4-nitrophenyl)-1,3-thiazole-2-amine showed the best activity with an inhibition rate of 43.21%.
Modulating Antimicrobial Activity and Mammalian Cell Biocompatibility with Glucosamine-Functionalized Star Polymers
Wong, Edgar H. H.,Khin, Mya Mya,Ravikumar, Vikashini,Si, Zhangyong,Rice, Scott A.,Chan-Park, Mary B.
, p. 1170 - 1178 (2016/03/22)
The development of novel reagents and antibiotics for combating multidrug resistance bacteria has received significant attention in recent years. In this study, new antimicrobial star polymers (14-26 nm in diameter) that consist of mixtures of polylysine and glycopolymer arms were developed and were shown to possess antimicrobial efficacy toward Gram positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (with MIC values as low as 16 μ mL-1) while being non-hemolytic (HC50 > 10 000 μ mL-1) and exhibit excellent mammalian cell biocompatibility. Structure function analysis indicated that the antimicrobial activity and mammalian cell biocompatibility of the star nanoparticles could be optimized by modifying the molar ratio of polylysine to glycopolymers arms. The technology described herein thus represents an innovative approach that could be used to fight deadly infectious diseases.
Design of glycosyltransferase inhibitors targeting human O-GlcNAc transferase (OGT)
Wang, Shuai,Shen, David L.,Lafont, Dominique,Vercoutter-Edouart, Anne-Sophie,Mortuaire, Marlène,Shi, Yun,Maniti, Ofelia,Girard-Egrot, Agnès,Lefebvre, Tony,Pinto, B. Mario,Vocadlo, David,Vidal, Sébastien
supporting information, p. 1172 - 1178 (2014/08/05)
Inhibition of glycosyltransferases requires the design of neutral inhibitors to allow cell permeation in contrast to their natural dianionic substrates. O-GlcNAc transferase (OGT) is a key enzyme involved in dynamic glycosylation of cytosolic and nuclear proteins in competition with phosphorylation. Designing OGT inhibitors is of prime interest for the better understanding of its biological implications. Introduction of a pyridine moiety as a pyrophosphate surrogate was evaluated, which provided moderate in vitro inhibition of OGT. Docking studies highlighted some key features for the binding of the designed inhibitors to the catalytic site of OGT where the carbohydrate moiety did not occupy its natural position but rather turned away and pointed to the solvent outside the catalytic pocket. Further investigation with cellular assays did not provide inhibition of OGT. This lack of OGT inhibition was rationalized with a permeation assay which revealed the sequestration of the inhibitors at the membrane. This journal is the Partner Organisations 2014.
Conversion of cysteine into dehydroalanine enables access to synthetic histones bearing diverse post-translational modifications
Chalker, Justin M.,Lercher, Lukas,Rose, Nathan R.,Schofield, Christopher J.,Davis, Benjamin G.
supporting information; experimental part, p. 1835 - 1839 (2012/04/04)
Six for the price of one: From a single precursor, dehydroalanine, six distinct post-translational modifications can be site-selectively installed on histone proteins (see figure), including the first site-selective phosphorylation and glycosylation of histones. Direct observation of histone deacetylase activity on a full-length modified histone as well as its interactions with both chromatin reader and writer/eraser proteins are reported.
Rapid-throughput competitive colorimetric assay based on monosaccharide-capped gold nanoparticles for detecting lectin-protein interactions
Tsai, Charng-Sheng,Chen, Chao-Tsen
, p. 314 - 322 (2014/01/17)
Identification of protein binding partners is one of key challenges in proteomics. A rapid-throughput competitive colorimetric assay is presented that uses gold nanoparticles capped by sugars such as mannopyranoside (Man-GNPs), N-acetylglucosamine (GlcNAc-GNPs), glucose (Glc-GNPs), or N-acetylgalactosamine (GalNAc-GNPs). The assay expediently detects protein-protein interactions in solution, particularly protein-lectin interactions. The competitive assays were conducted in microtiter plates; ten proteins (two glycoproteins and eight lectins) and three sugar-binding lectins (concanavalin A (ConA), wheat germ agglutinin (WGA), and Ricinus communis agglutinin (RCA120)) were combinatorially arranged in a 30-well plate, and constant concentrations of the monosaccharide-capped GNPs (sugar-GNPs) were added to each well. If interactions occurred between the proteins, the sugar-GNPs retained their burgundy color. If no interactions occurred between the proteins, the sugar-GNPs were agglomerated by the corresponding binding lectin, thus producing a blue color. Several new binding pairs were identified for the first time by using this assay, and the binding constants and stoichiometric ratios were determined on the basis of the wavelength shifts. The results were further verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence resonance energy transfer (FRET) spectroscopy. The assay is very sensitive, requiring only nanomolar protein concentrations.
Olefin cross-metathesis on proteins: Investigation of allylic chalcogen effects and guiding principles in metathesis partner selection
Lin, Yuya A.,Chalker, Justin M.,Davis, Benjamin G.
supporting information; experimental part, p. 16805 - 16811 (2011/02/17)
Olefin metathesis has recently emerged as a viable reaction for chemical protein modification. The scope and limitations of olefin metathesis in bioconjugation, however, remain unclear. Herein we report an assessment of various factors that contribute to productive cross-metathesis on protein substrates. Sterics, substrate scope, and linker selection are all considered. It was discovered during this investigation that allyl chalcogenides generally enhance the rate of alkene metathesis reactions. Allyl selenides were found to be exceptionally reactive olefin metathesis substrates, enabling a broad range of protein modifications not previously possible. The principles considered in this report are important not only for expanding the repertoire of bioconjugation but also for the application of olefin metathesis in general synthetic endeavors.
Synthesis of 1-C-linked diphosphate analogues of UDP-N-Ac-glucosamine and UDP-N-Ac-muramic acid
Babi?, Andrej,Gobec, Stanislav,Gravier-Pelletier, Christine,Le Merrer, Yves,Pe?ar, Slavko
, p. 9093 - 9100 (2008/12/22)
UDP-N-acetyl-glucosamine and UDP-N-acetyl-muramic acid are two important cytoplasmic precursors of bacterial peptidoglycan. The convergent synthesis of their analogues is reported. The α-1-C-linked-N-acetyl-glucosamine was synthesized using microwave-assisted Keck radical allylation. Oxidation of alkene derivatives to the corresponding carboxylic acids allowed attachment to O- and N-sulfamoyluridine giving stable diphosphate mimetics.
