- Site-specific effect of polar functional group-modification in lipids of TLR2 ligands for modulating the ligand immunostimulatory activity
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Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family, recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have focused on the property of the hydrophobic TLR2 pocket. Based on the X-ray crystal structure of TLR2, small polar regions were found in the hydrophobic TLR2 pocket. Interactions between the polar residues and ligands were explored here by designing and synthesizing a Pam2CSK4 derivative of the TLR2 ligands, containing an amide group within the lipid moiety. We evaluated the binding affinities and immunomodulatory activities of these ligands. Results suggested that the amide groups in the lipid chain interacted with the polar residues in the hydrophobic lipid-binding pocket of TLR2.
- Arai, Yohei,Inuki, Shinsuke,Fujimoto, Yukari
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- Enzymatic syntheses of N-lauroyl-β-alanine homologs in organic media
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Enzymatic amidation of the primary amines β-alanine ethyl ester and 3-aminopropionitrile with methyl laurate by means of immobilized lipase (Candida antarctica lipase, CAL) resulted in the formation in good yield of N-lauroyl-β-alanine ethyl ester and 3-(N-lauroylamino)-propionitrile, respectively. When 3-amino-propionitrile was used as substrate, diisopropyl ether was a suitable solvent. Changing the reaction temperature (12-80 °C) did not affect the yields, and room temperature was a suitable temperature for this reaction. In the investigation of reaction conditions, the use of equimolar amounts (5 mmol) of substrate and ester, along with 0.5 g of CAL, in diisopropyl ether gave the best yield (99.3%) after 24 h of incubation at 24 °C. The enzyme activity in the amidation reaction did not decrease even after six uses. With β-alanine ethyl ester hydrochloride as substrate, diisopropyl ether was unsuited as a solvent owing to the low solubility of the substrate in this solvent. In this reaction, the best yield (82.0%) was attained by using dioxane as solvent. CAL achieved higher extents of amide synthesis with long-chain than with short-chain ester substrates. The enzyme accepted only nonbulky primary amines as substrates.
- Izumi,Yagimuma,Haga
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Read Online
- Preparation method of surfactant containing amino acid and glucose
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The invention provides a preparation method of a surfactant containing beta-amino acid and glucose. The preparation method comprises the steps: the beta-amino acid is alkalized and then reacts with fatty acid methyl ester to obtain N-fatty acyl group-beta-amino acid, then the N-fatty acyl group-beta-amino acid reacts with diamine to obtain N-fatty acyl group-beta-amino acid amide, and finally theN-fatty acyl group-beta-amino acid amide reacts with the glucose to prepare N-fatty acyl group-beta-amino acid amide osamine. According to a preparation process of the N-fatty acyl group-beta-amino acid amide osamine containing the beta-amino acid and the glucose, preparation is easy, high-toxicity reagents and hydrogenation reduction reagents do not need to be added, thus pollution to the environment is reduced, product purification is easy, the yield is high, and performance of high surface tension is achieved.
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Paragraph 0022-0023
(2020/01/14)
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- Deciphering the potentiometric properties of (porphinato)zinc(ii)-derived supramolecular polymers and related superstructures
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Because modulating the structure-function relationships of π-conjugated superstructures opens fresh opportunities to tune the electronic structures of semiconducting materials, self-assembled architectures have emerged as pivotal candidates to engineer optoelectronic devices. While the photophysical and electrical properties of 1-dimensional supramolecular polymers have been extensively explored, establishing their fundamental potentiometric properties using reliable electrochemical measurements has been less scrutinized and would benefit the engineering of semiconducting materials. In this regard, elucidating the energy level of valence and conduction bands that delineate the electronic structure of self-assemblies is critical to unveiling the parameters that regulate their structure-function properties. In the present contribution, design principles to engineer 2-dimensional nanosheets, nanowires, fibers and amorphous solids from (porphinato)zinc(ii) (PZn) building blocks have been elucidated by modifying the structural properties of the side chains that flank PZn-based cores. As these self-assemblies feature identical redox-active building blocks but evidence different solid-state morphologies, the elucidation of their potentiometric properties reveals important structural parameters that regulate the potentials at which holes and electrons are injected into the valence and conduction bands of these hierarchical materials. While self-assembly conformations modestly impact valence band energies, superstructures built from H-type aggregates feature a conduction band energy stabilized by more than 350 meV with respect to those constructed from J-type aggregates.
- Liu, Chuan,Liu, Kaixuan,Klutke, Jared,Ashcraft, Adam,Steefel, Samantha,Olivier, Jean-Hubert
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supporting information
p. 11980 - 11991
(2018/11/26)
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- Structure, supramolecular organization and phase behavior of N-acyl-β-alanines: Structural homologues of mammalian brain constituents N-acylglycine and N-acyl-GABA
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N-Acyl-β-alanines (NABAs) are structural homologues of N-acylglycines (NAGs) and N-acyl-γ-aminobutyric acids (NAGABAs), and achiral isomers of N-acylalanines, which are all present in mammalian brain and other tissues and modulate activity of biological receptors with various functions. In the present study, we synthesized and characterized a homologous series of NABAs bearing saturated acyl chains (n = 8-20) and investigated their supramolecular organization and thermotropic phase behavior. In differential scanning calorimetric (DSC) studies, most of the NABAs gave one or two minor transitions before the main chain-melting phase transition in the dry state as well as upon hydration with water, but gave only a single transition when hydrated with buffer (pH 7.6). Transition enthalpies (ΔHt) and entropies (ΔSt), obtained from the DSC studies showed linear dependence on the chain length in the dry state and upon hydration with buffer, whereas odd-even alteration was observed when hydrated with water. The crystal structures of N-lauroyl-β-alanine (NLBA) and N-myristoyl-β-alanine (NMBA) were solved in monoclinic system in the P21/c space group. Both NLBA and NMBA were packed in tilted bilayers with head-to-head (and tail-to-tail) arrangement with tilt angles of 33.28° and 34.42°, respectively. Strong hydrogen bonding interactions between [sbnd]COOH groups of the molecules from opposite leaflets as well as N[sbnd]H?O hydrogen bonds between the amide groups from adjacent molecules in the same leaflet as well as dispersion interactions between the acyl chains stabilize the bilayer structure. The d-spacings calculated from powder X-ray diffraction studies showed odd-even alteration with odd-chain length compounds exhibiting higher values as compared to the even-chain length ones and the tilt angles calculated from the PXRD data are higher for the even chain NABAs. These observations are relevant to developing structure-activity relationships for these amphiphiles and understand how NABAs differ from their homologues and isomers, namely NAGs, NAGABAs, and N-acylalanines.
- Sivaramakrishna,Swamy, Musti J.
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- Molecular structural requirements, dye specificity, and application of anionic peptide amphiphiles that induce intense fluorescence in cationic dyes
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We have previously reported that a double-chain anionic amphiphile capable of intermolecular triple hydrogen bonds could form extremely hydrophobic sites in water and specifically incorporated stilbazolium-based compact hemicyanine dyes as monomeric species, resulting in induction of intense fluorescence emission in the dyes. In this paper, the structural requirements of the intense fluorescence-inducing amphiphiles were investigated. It is noted that the introduction of β-Ala residues into two long-chain alkyl group moieties was most effective for the amphiphiles derived from L-glutamic acid with relatively shorter side-chain methylenes. The dye specificity in terms of induction of the intense fluorescence was also investigated using hemicyanines (stilbazolium etc.), cyanine, carbocyanine, thiacarbocyanines, and azo dye. The amphiphile with the shortest octanoyl-β-alanyl double-chain alkyl groups, longer side-chain, and shorter spacer was found to show increased sensitivity to alkali metal ions, especially Li+. This could be a potential OFF-ON type fluorescence sensor for Li+. The Royal Society of Chemistry 2009.
- Hachisako, Hiroshi,Ryu, Naoya,Murakami, Ryoichi
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supporting information; experimental part
p. 2327 - 2337
(2009/09/26)
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- Design, synthesis and early structure-activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate
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Inhibition of the farnesylation of ras proteins has been identified as a promising target in tumor therapy. Only a few farnesyltransferase inhibitors are bisubstrate analogues displaying features of both substrates, the farnesylpyrophosphate and the C-terminal CAAX-tetrapeptide sequence of the ras protein. These known bisubstrate analogues consist of an AAX-tripeptide and a farnesyl residue connected through various linkers. We have developed a class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures. Long chain fatty acids and aryl-substituted carboxylic acids were used as farnesyl surrogates. These structures were linked to isoleucine amide, benzoic acid amide, N-substituted aminobenzenesulfonamides and N(α)-aryl-substituted methionine derivatives, respectively, which function as AA- or AAX-mimetics. Copyright (C) 2000 Elsevier Science Ltd.
- Schlitzer, Martin,Boehm, Markus,Sattler, Isabel,Dahse, Hans-Martin
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p. 1991 - 2006
(2007/10/03)
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- Processes for the preparation of N-(long-chain acyl)amino acid and salt thereof, and intermediate amidonitrile and process for the preparation thereof
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To provide processes suitable for industrial production by which high-purity N-(long-chain acyl)amino acid and salt thereof can be prepared from inexpensive raw materials. An alkyl ester of a fatty acid (2) is reacted with an aminonitrile (3) in the presence of a basic catalyst to form an amidonitrile (1), the amidonitrile (1) is hydrolyzed into an N-(long-chain acyl)amino acid salt (4) in the presence of a basic substance, the pH of the resulting aqueous solution is adjusted to a pH from 1 to 5 with a mineral acid to form an N-(long-chain acyl)amino acid (5), and this amino acid is recovered. STR1 wherein R1 CO-- represents a fatty acid residue having 8 to 22 carbon atoms; R2 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; R3 represents an alkylene group having 1 to 5 carbon atoms; R4 represents an alkyl group having 1 to 4 carbon atoms; and M represents a monovalent cation.
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- Synthesis and antitumor activities of glycine-exchanged analogs of spicamycin
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A series of SPM VIII analogs were synthesized to investigate the effect of the amino acid moiety on the antitumor activity. The L-threonine analog and the glycylglycine analog of SPM VIII showed much higher cytotoxity to P388 murine leukemia cells (IC50 5.8 nM and 0.11 nM, respectively) than SPM VIII (IC50 25 nM). However, replacement of the glycine moiety with other amino acids greatly reduced the antitumor activity against COL-1 human colon cancer xenograft model. This study indicated that the glycine moiety of SPM VIII is crucial for the antitumor effect.
- Sakai,Kawai,Kamishohara,Odagawa,Suzuki,Uchida,Kawasaki,Tsuruo,Otake
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p. 504 - 508
(2007/10/02)
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- Formation of unusual side-products from succinimidyl esters of fatty acids during the acylation of amino acids
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A new side-product, succinohydroxamic decanoic anhydride, was isolated from the reaction mixture during the acylation of lysine by succinimidyl decanoate in the presence of aqueous sodium hydroxide.Lauric and palmitic acid derivatives were also obtained.I
- Paquet, Alenka,Bergeron, Michel
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p. 1806 - 1808
(2007/10/02)
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