- Further Insights on Structural Modifications of Muramyl Dipeptides to Study the Human NOD2 Stimulating Activity
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A series of muramyl dipeptide (MDP) analogues with structural modifications at the C4 position of MurNAc and on the d-iso-glutamine (isoGln) residue of the peptide part were synthesized. The C4-diversification of MurNAc was conveniently achieved by using CuAAC click strategy to conjugate an azido muramyl dipeptide precursor with structurally diverse alkynes. d-Glutamic acid (Glu), replaced with isoGln, was applied for the structural diversity through esterification or amidation of the carboxylic acid. In total, 26 MDP analogues were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response. Interestingly, MDP derivatives with an ester moiety are found to be more potent than reference compound MDP itself or MDP analogues containing an amide moiety. Among the varied lengths of the alkyl chain in ester derivatives, the MDP analogue bearing the d-glutamate dodecyl (C12) ester moiety showed the best NOD2 stimulation potency.
- Cheng, Wei-Chieh,You, Ting-Yun,Teo, Zhen-Zhuo,Sayyad, Ashik A.,Maharana, Jitendra,Guo, Chih-Wei,Liang, Pi-Hui,Lin, Chung-Shun,Meng, Fan-Chun
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p. 3836 - 3844
(2020/10/21)
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- Synthesis of Diverse N-Substituted Muramyl Dipeptide Derivatives and Their Use in a Study of Human NOD2 Stimulation Activity
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A flexible synthetic strategy toward the preparation of diverse N-substituted muramyl dipeptides (N-substituted MDPs) from different protected monosaccharides is described. The synthetic MDPs include N-acetyl MDP and N-glycolyl MDP, known NOD2 ligands, and this methodology allows for structural variation at six positions, including the muramic acid, peptide, and N-substituted moieties. The capacity of these molecules to activate human NOD2 in the innate immune response was also investigated. It was found that addition of the methyl group at the C1 position of N-glycolyl MDP significantly enhanced the NOD2 stimulating activity.
- Chen, Kuo-Ting,Huang, Duen-Yi,Chiu, Cheng-Hsin,Lin, Wan-Wan,Liang, Pi-Hui,Cheng, Wei-Chieh
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p. 11984 - 11988
(2015/08/18)
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- Chemical synthesis and anti-tumor and anti-metastatic effects of dual functional conjugate
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The present invention discloses chemical synthesis, anti-tumor and anti-metastatic effects of a dual functional conjugate as shown by formula I. Specifically, paclitaxel or docetaxol is linked with muramyl dipeptide derivative to form a conjugate, thus dual anti-tumor and anti-metastatic effects are achieved by combination of chemotherapy and immunotherapy. The present invention also discloses that paclitaxel or docetaxol and muramyl dipeptide derivative conjugate is synthesized by combination of solid-phase and solution-phase synthesis, and said conjugate can be used in manufacture of anti-tumor medicaments as proved by reliable bioassays.
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Page/Page column
(2015/07/27)
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- CHEMICAL SYNTHESIS AND ANTI-TUMOR AND ANTI-METASTATIC EFFECTS OF DUAL FUNCTIONAL CONJUGATE
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The present invention discloses chemical synthesis, anti-tumor and anti-metastatic effects of a dual functional conjugate as shown by formula I. Specifically, paclitaxel or docetaxol is linked with muramyl dipeptide derivative to form a conjugate, thus dual anti-tumor and anti-metastatic effects are achieved by combination of chemotherapy and immunotherapy. The present invention also discloses that paclitaxel or docetaxol and muramyl dipeptide derivative conjugate is synthesized by combination of solid-phase and solution-phase synthesis, and said conjugate can be used in manufacture of anti-tumor medicaments as proved by reliable bioassays.
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Page/Page column
(2013/06/26)
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- DENTAL FILLING REPAIR KIT
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Provided is a filling/restoring material, including a photopolymerization initiator of a quaternary system formed by combining an a-diketone compound, an aliphatic amine compound, an aromatic amine compound, and a photoacid generator, in which even when the filling/restoring material is filled and cured on a cured layer of a dental adhesive material including a radical-polymerizable monomer having an acidic group, the filling/restoring material undergoes sufficient curing up to a contact interface between the filling/restoring material and the cured layer, thereby providing high adhesive strength stably. Also provided is a dental filling/restoration kit, including: a filling/restoring material (A) including: a polymerizable monomer having no acidic group (I); a basic inorganic material (II); and a photopolymerization initiator (III) formed by at least combining: an a-diketone compound (i); an aliphatic amine compound (ii); an aromatic amine compound (iii) ; and a photoacid generator (iv); and an adhesive material (B), which is used for adhesion between a tooth and the filling/restoring material by curing the adhesive material before filling the filling/restoring material, the adhesive material including: a polymerizable monomer including a polymerizable monomer having an acidic group (I); and a polymerization initiator (II).
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- CONTROL OF SPORE GERMINATION
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Provided are compositions and methods for treating bacterial infections. It is demonstrated herein that bacteria cell wall materials stimulate germination of spores of Gram-positive bacteria, and that such activity requires Ser/Thr kinase PrkC. By modulating one or both, spores (which can be antibiotic resistant) can be stimulated or inhibited from germination, which can be exploited in various methods of therapeutic treatment. Also provided is a method of modulating germination of a spore of a Gram-positive bacterium. Also provided is a method of decontaminating an environment.
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- ONE-PACK TYPE COATING MATERIAL FOR TOOTH SURFACE
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[Problems] To provide a one-package type tooth surface coating material that is capable of forming, on the surface of a tooth, a cured film having not only a very high strength of adhesion to the tooth surface but also excellent properties such as long-term adhesion, long-term durability, dentinal tubule occlusion and aesthetic appearance, and that has excellent storage stability and can be stored in the form of one package. [Means for Solution] A one-package type tooth surface coating material comprising (A) a polymerizable monomer component containing not less than 5% by mass of an acidic group-containing polymerizable monomer; (B) polyvalent metal ions; (C) a volatile water-soluble organic solvent; (D) water; and (E) an effective amount of a photopolymerization initiator; the amount of the polyvalent metal ions (B) and the amount of the volatile water-soluble organic solvent (C) satisfying a specific relationship.
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- Organophosphorus compounds for dental polymerizable compositions
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An organic phosphate compound having at least one radically polymerizable double bond, at least one phosphate residue having one or two hydroxyl groups, and at least one hydrocarbon group having 4 or more carbon atoms in a molecule, wherein a 10% by weight methanol solution of the organic phosphate compound has an electric conductivity at 25° C. of 0.5 mS/cm or less, and/or the organic phosphate compound has a light transmittance at 455 nm of 90% or more; a process for preparing the organic phosphate compound; a dental polymerizable composition comprising (a) the organic phosphate compound and (b) a polymerizable monomer capable of copolymerizing with the organic phosphate compound.
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- VINYL ETHER DERIVATIVES
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Processes for the manufacture of vinyl ether derivatives, e.g., methoxydihydropyran, are disclosed which comprise reacting acetylene and a lower alcohol, e.g., methanol, to form a vinyl alkyl ether, e.g., vinyl methyl ether, reacting the vinyl alkyl ether so produced with an alpha , beta -unsaturated carbonylic compound, e.g., acrolein, in the presence of the lower alcohol to preferably enhance the conversion of the vinyl alkyl ether to the vinyl ether derivative. In one aspect of the invention, the vinyl ether derivative is methoxydihydropyran which is subjected to hydrolysis to form glutaraldehyde.
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- Polymeric immunological adjuvants
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Adjuvants for enhancing the immune response to an antigen are provided comprising the adjuvant incorporated into a lipid layer where the adjuvant is covalently or non-covalently involved in a polymeric system. Conveniently, the adjuvant may be conjugated to a polymerizable group and co-polymerized with a water-soluble and/or amphiphilic polymerizable monomer or combined with a polymerized amphiphile. The adjuvant and antigen may then be administered to a mammalian host to obtain enhanced immune response.
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- Feline leukemia virus antigen vaccines
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A vaccine for immunizing animals against Feline Leukemia Virus (FeLV) infections contains an FeLV antigen emulsified with a polyoxypropylene-polyoxyethylene block polymer, a glycol ether-based surfactant, an immunopotentiating amount of an immunostimulating glycopeptide, and, optionally, a metabolizable non-toxic oil.
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- Lipophile derivatives of muramylpeptides having properties of activating macrophages and compositions containing them
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The invention relates to muramyleptide derivatives resulting essentially from the conjugation or the coupling, as the case may require, through an arm, between a muramylpeptide and a group containing two atoms contiguous with one another to each of which is attached a lipophile chain comprising from 8 to 100 carbon atoms, preferably from 14 to 24 carbon atoms. The derivatives according to the invention are endowed with remarkable stimulating properties with respect to the activation of macrophages, of which they amplify the tumoricidal properties.
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- Vaccines comprising polyoxypropylene-polyoxyethylene block polymer based adjuvants
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A vaccine contains an immunologically effective amount of an antigen, a polyoxypropylene-polyoxyethylene block polymer, a glycol ether-based surfactant, an immunopotentiating amount of an immunostimulating glycopeptide, and, optionally, a metabolizable non-toxic oil.
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- Method for enhancing the anti-infective activity of muramyldipeptide derivatives
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Co-administration of a muramyldipeptide derivative with liposomes enhances the anti-infective activity of the muramyldipeptide derivative.
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- Polyoxypropylene-polyoxyethylene block polymer based adjuvants
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A method for enhancing the immunogenicity of an antigen is emulsifying it with a polyoxypropylene-polyoxyethylene block polymer, a glycol ether-based surfactant, a metabolizable non-toxic oil, isoosmotic saline, and an immunopotentiating amount of an immunostimulating glycopeptide.
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- Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
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Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides.
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- SYNTHESIS AND FAST-ATOM-BOMBARDMENT-MASS SPECTROMETRY OF N-ACETYLMURAMOYL-L-ALANYL-D-ISOGLUTAMINE (MDP)
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N-Acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) was synthesized by a series of condensation of appropriate reagents, followed by hydrogenolysis.Each intermediate step resulted in a stable, crystalline product.D-Isoglutamine 4-benzyl ester was condensed with N-(tert-butoxycarbonyl)-L-alanine N-hydroxysuccinimide ester, to give N-(tert-butoxycarbonyl)-L-alanyl-D-isoglutamine benzyl ester.Condensation of L-alanyl-D-isoglutamine benzyl ester with N-acetyl-1-O-benzyl-4,6-O-benzylidenemuramic acid, followed by hydrogenolysis, gave MDP.The synthetic scheme was shown to be capable of producing gram quantities of highly pure MDP, as well as a few of its analogs.The synthetic MDP was characterized by analytical and biological methods, and it was found that the use of fast-atom-bombardment-mass spectrometry may greatly simplify the characterization process.
- Phillips, Lawrence R.,Nishimura, Osamu,Fraser, Blair A.
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p. 275 - 286
(2007/10/02)
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- Synthesis of a Biologically Active Fluorescent Muramyl Dipeptide Congener
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A fluorescent-labeled muramyl dipeptide (MDP) has been prepared to probe immunoadjuvant cellular interactions.N-Acetylmuramyl-L-alanyl-D-isoglutamine (1) was synthesized in improved yield and reacted with 2-(fluoroesceinylamino)-4,6-dichloro-s-triazine (DTAF,2) to give the fluorescent adduct DTAF-MDP (3), attached through the 6-position of the sugar moiety.Adjuvant activity was assessed by using two different in vitro assays, macrophage spreading, and inhibition of macrophage migration.Both assays indicated that the apparent adjuvant activity of 3 is comparable to that of 1.
- Hiebert, C. K.,Kopp, W. C.,Richerson, H. B.,Barfknecht, C. F.
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p. 1729 - 1732
(2007/10/02)
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