- Bacterial flavoprotein monooxygenase YxeK salvages toxic S-(2-succino)-adducts via oxygenolytic C–S bond cleavage
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Thiol-containing nucleophiles such as cysteine react spontaneously with the citric acid cycle intermediate fumarate to form S-(2-succino)-adducts. In Bacillus subtilis, a salvaging pathway encoded by the yxe operon has recently been identified for the detoxification and exploitation of these compounds as sulfur sources. This route involves acetylation of S-(2-succino)cysteine to N-acetyl-2-succinocysteine, which is presumably converted to oxaloacetate and N-acetylcysteine, before a final deacetylation step affords cysteine. The critical oxidative cleavage of the C–S bond of N-acetyl-S-(2-succino)cysteine was proposed to depend on the predicted flavoprotein monooxygenase YxeK. Here, we characterize YxeK and verify its role in S-(2-succino)-adduct detoxification and sulfur metabolism. Detailed biochemical and mechanistic investigation of YxeK including 18O-isotope-labeling experiments, homology modeling, substrate specificity tests, site-directed mutagenesis, and (pre-)steady-state kinetics provides insight into the enzyme’s mechanism of action, which may involve a noncanonical flavin-N5-peroxide species for C–S bond oxygenolysis.
- Ellis, Holly R.,Kammerer, Bernd,Lagies, Simon,Matthews, Arne,Sch?nfelder, Julia,Schleicher, Erik,Stull, Frederick,Teufel, Robin
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- Separation and purification method for acetylcysteine enantiomer
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The invention discloses a separation and purification method for an acetylcysteine enantiomer. The separation and purification method is characterized in that an N-acetylcysteine enantiomer is separated by adopting high performance liquid chromatography; a mobile phase in the high performance liquid chromatography is an alkane solvent-isopropanol, and a volume ratio of the alkane solvent to the isopropanol is (70-83):(17-30); and the filler of a chromatographic column in the high performance liquid chromatography is a filler coated with a cellulose derivative represented by formula I. The separation and purification method can effectively separate the N-acetyl-L-cysteine and its enantiomer, further realizes the qualitative and quantitative analysis of the N-acetyl-L-cysteine and its enantiomer, and is of guiding significance for drug production and quality improvement.
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Paragraph 0062-0128
(2020/01/12)
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- Preparation method of N-acetyl-L-cysteine
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The invention belongs to the field of organic synthesis and particularly relates to a preparation method of N-acetyl-L-cysteine. In the method, with cysteine being a raw material and acetic anhydridebeing an acylating agent, the N-acetyl-L-cysteine is prepared through a one-step direct acylation reaction. In the method, the optimum pH value range is disclosed and a recrystallization reagent is determined; meanwhile, by means of a sectional temperature control method, the yield and mass percentage of the product are greatly increased, wherein the finish yield of the product is 80-85% and the mass percentage can reach more than 99%. The method can greatly reduce production cost and reaction steps, and has excellent industrial prospect.
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Paragraph 0013-0017
(2019/05/15)
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- Peptide Tyrosinase Activators
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Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
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- Synthetic approaches to obtain amino acid adducts of 4,4′- methylenediphenyl diisocyanate
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4,4′-Methylenediphenyl diisocyanate (MDI) is the most important isocyanate used in the chemical industry. Lung sensitization and asthma are the main types of damage after exposure to MDI. Albumin adducts of MDI might be involved in the etiology of sensitization reactions. It is therefore necessary to have sensitive and specific biomarkers such as blood protein adducts to monitor people exposed to isocyanates. For the discovery of new isocyanate adducts with blood proteins present in vivo, new synthetic standards are needed. To achieve this, we developed five methods to obtain amino acid adducts of MDI. We synthesized and isolated MDI adducts of aspartic acid, glutamic acid, cysteine, and valine. The new adducts were characterized by LC-MS/MS and NMR. We synthesized the corresponding isotope-labeled MDI adducts to develop analytical methods using LC-MS/MS. Glutathione adducts of isocyanates are an important way of transportation of the reactive isocyanates to distant sites from the original site of exposure. Therefore, we used N-acetyl-cysteine adducts of MDI as reactants: N-acetyl-S-[[4-(4-aminobenzyl)phenyl]carbamoyl]-cysteine (MDI-AcCys) and N-acetyl-S-[[4-(4-acetylaminobenzyl)phenyl]carbamoyl]-cysteine (AcMDI-AcCys). MDI-AcCys or AcMDI-AcCys formed adducts with albumin, N α-acetyl lysine, and valine. Isotope-labeled albumin adducts (= d4-MDI-albumin) were synthesized from d4-MDI-AcCys and albumin. d4-MDI-albumin can be used as an internal standard to analyze biological samples. Such an internal standard will not correct only for the extraction recovery of the adducts but also for the potential variation of the enzymatic digestions used in the procedure to analyze albumin adducts of MDI. The synthetic procedures described in this manuscript will be applicable to the synthesis of amino acid adducts from other isocyanates.
- Sabbioni, Gabriele,Dongari, Nagaraju,Schneider, Siegfried,Kumar, Anoop
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p. 2704 - 2714
(2013/02/23)
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- BINARY AND TERTIARY GALVANIC PARTICULATES AND METHODS OF MANUFACTURING AND USE THEREOF
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The present invention relates to galvanic particulates, their methods of manufacture and uses in treatments are described. The galvanic particulates may be binary or tertiary galvanic particulates, for example, containing multiple layers or phases of conductive materials.
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- Combination Therapies for Treating Metabolic Disorders
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This invention is directed to pharmaceutical combinations comprising an antioxidant agent, an anti-inflammatory agent, and optionally at least one other anti-diabetic agent useful for treating metabolic disorders. This invention also encompasses pharmaceutically acceptable compositions comprising an antioxidant agent, an anti-inflammatory agent, optionally at least one other anti-diabetic agent, and at least one pharmaceutically acceptable carrier. The combinations and compositions of this invention are useful as methods for treating metabolic disorders including diabetes, particularly Type I and Type II diabetes, as well as diseases and disorders associated with diabetes, including but not limited to atherosclerosis, cardiovascular disease, inflammatory disorders, nephropathy, neuropathy, retinopathy, β-cell dysfunction, dyslipidemia, LADA, metabolic syndrome, hyperglycemia, insulin resistance, and/or chronic obstructive pulmonary disease in a mammal, particularly a diabetic mammal, and specifically a human patient. This invention is particularly directed to pharmaceutical compositions comprising an lipoic acid, one or more anti-inflammatories selected from the group consisting of diflunisal, diclofenac, dexibuprofen, dexketoprofen, naproxen, and salicylate, and optionally one or more pharmaceutically acceptable carriers. The compositions of this invention are useful as methods for treating metabolic disorders including type II diabetes, insulin resistance, beta-cell dysfunction, and hyperglycemia in a patient, particularly a diabetic patient.
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- Pharmaceutically acceprable salts of aporphine compounds of carboxyl group-containing agents and methods for preparing the same
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The present invention discloses novel pharmaceutically acceptable salts of aporphine compounds and carboxyl-group containing agents. Also, the present invention discloses methods for preparing the pharmaceutically acceptable salts. These pharmaceutically acceptable salts are suitable for use in treating and/or preventing hyperglycemic disease and/or several oxidative stress related diseases.
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- COMPOSITION FOR TREATING SULFUR MUSTARD TOXICITY AND METHODS OF USING SAME
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One embodiment of the present invention provides a composition, comprising, in amounts effective to treat sulfur mustard or half sulfur mustard induced toxicity or skin damage: an agent that inhibits alkylation of —SH and >NH protein groups; an agent that reduces —SS— to SH; a scavenger of reactive oxygen species; a substrate that maintains tissue reduction-oxidation status; an agent that protects against invading inflammatory cells and associated oxidative stress; an antagonist of prostaglandin synthesis; and an agent that induces tissue regeneration. Methods of using the composition are also provided.
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- Liver function improvement formulation
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A food supplement formulation effective to improve the function of the liver comprises selenium, milk thistle seed, phosphatidyl choline, dandelion root, l-methionine, l-taurine, N-acetyl-cysteine, alpha lipoic arid, artichoke leaf, green tea leaf, turmeric root, belleric myrobalan fruit, boerhavia diffusa, eclipta alba, wedelolactones tinospora cordifolia, andrographis paniculata, and picrorhiza kurroa.
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- Anti-aging nutritional supplement
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An anti-aging nutritional supplement composition includes vitamins, minerals, an inflammatory process support, a blood sugar/insulin support, a botanical antioxidants, a methylating factor, a DNA repair agent, a fat metabolizer, an absorption enhancer, a brain function support, whole foods, a cellular energizer, a nucleotide precursor, amino acids, a fatty acid complex, and digestive enzymes. The composition supplies nutritional supplements necessary for proper glycation, DNA methylation, anti-oxidation, and control of inflammatory processes. The composition and the method of use provide an effective anti-aging treatment by decreasing DNA damage, increasing DNA repair, and improving immune function of human body.
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- Synthesis of N,N-dimethyl-2,4-dinitro-5-fluorobenzylamine and its reactions with amino acids and peptides
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A practical synthesis is described for N,N-dimethyl-2,4-dinitro-5- fluorobenzylamine (DMDNFB) and its -d6 analog as an alternative Sanger's reagent (DNFB), for purposes of amino acid derivatization detectable by positive mode electrospray ionization mass spectrometry. DMDNFB is comparable to DNFB in its efficiency to derivatize amino acids and peptides. Various DMDNP (d0/d6) derivatives of (modified) lysine were synthesized to evaluate the potential use of isotope-edited LC-ESI-MS as a tool for structural definition of the posttranslational modification of protein-based lysines.
- Liu, Zhongfa,Sayre, Lawrence M.
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p. 1601 - 1610
(2007/10/03)
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- Homogeneous polyoxime compositions and their preparation by parallel assembly
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Provided by this invention are essentially homogeneous, defined compositions of matter comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.
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- Compositions and methods for prevention and treatment of chronic diseases and disorders including the complications of diabetes mellitus
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This invention relates to nutrient and therapeutic compositions for treatment and prevention of symptoms and disease conditions associated with microangiopathy and macroangiopathy and to methods using the compositions. In particular, the invention relates to compositions useful in the treatment of diabetic retinopathy and nephropathy, to compositions useful in the treatment of other retinal disorders including macular degeneration and cataracts, to compositions useful in wound healing, to compositions useful for treatment and prevention of neuropathy, to compositions useful for treatment and prevention of cardiovascular disease and to compositions useful for the treatment and prevention of dental and periodontal disorders.
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- Reactivity of sulfur nucleophiles towards S-nitrosothiols
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Rate constants have been measured for the reactions of a range of S-nitrosothiols with the following sulfur-centred nucleophiles: sulfite ion, thiourea, thiocyanate ion, thiosulfate ion, thiomethoxide ion and sulfide ion. Many of the reactions were very fast and were followed in a stopped-flow spectrophotometer. For the sulfite reaction the reactive species over the pH range 4-8 was shown to be exclusively SO32-. For two RSNO species the reactivity sequence was established as: SO32- > MeS- > S2O32- ? SC(NH2)2 SCN-. The reaction with sulfide ion was also rapid and generated a fairly stable yellow species (λmax 410 nm), which was probably the nitrosodisulfide ion ONSS-, but the absorbance-time data were too complex for a simple kinetic analysis. This reaction could have some potential as an analytical procedure for the determination of RSNO species. The kinetic results are discussed in terms of the factors affecting nucleophilicity and are compared with the corresponding reactions of other nitrosating species.
- Munro, Andrew P.,Williams, D. Lyn H.
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p. 1794 - 1797
(2007/10/03)
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- Reaction of ascorbic acid with S-nitrosothiols: Clear evidence for two distinct reaction pathways
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Ascorbate reacts with S-nitrosothiols generally, in the pH range 3-13 by way of two distinct pathways, (a) at low [ascorbate], typically below ～1 × 10-4 mol dm-3 which leads to the formation of NO and the disulfide, and (b) at higher [ascorbate] when the products are the thiol and NO. Reaction (a) is Cu2+-dependent, and is completely cut out in the presence of EDTA, whereas reaction (b) is totally independent of [Cu2+] and takes place readily whether EDTA is present or not. For S-nitrosoglutathione (GSNO) the two reactions can be made quite separate, although for some reactants the two reactions overlap. In reaction (a), ascorbate acts as a reducing agent, generating Cu+ from Cu2+, which in turn reacts with RSNO forming initially NO, Cu2+ and RS-. The latter can then play the role of reducing agent for Cu2+, leading to disulfide formation. Ascorbate will initiate reaction when the free thiolate has initially been reduced to a very low level by the synthesis of RSNO from a large excess of nitrous acid over the thiol. Reaction (b) is interpreted in terms of nucleophilic attack by ascorbate at the nitroso-nitrogen atom, leading to thiol and O-nitrosoascorbate which breaks up, by a free-radical pathway, to give dehydroascorbic acid and NO. A similar pathway is the accepted mechanism in the literature for the nitrosation of ascorbate by nitrous acid and alkyl nitrites. The rate constant for the Cu2+-independent pathway increases sharply with pH and analysis of the variation of the rate constant with pH identifies a reaction pathway via both the mono- and di-anion forms of ascorbate, with the latter being the more reactive. As expected the entropy of activation is large and negative. Some aspects of structure-reactivity trends are discussed.
- Holmes, Anthony J.,Williams, D. Lyn H.
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p. 1639 - 1644
(2007/10/03)
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- Hetero-polyoxime compounds and their preparation by parallel assembly
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Provided by this invention are defined compositions of hetero-polyoximes of defined structure comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.
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- Indane-2-mercaptoacetylamide disulfide derivatives useful as inhibitors of enkephalinase
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The present invention relates to certain novel indane-2-mercaptoacetylamide disulfide derivatives of the formula STR1 useful as inhibitors of enkephalinase.
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamine derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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- LINAC/LASER determination of the absolute rate constant for thiyl and hydroxyl radical reaction with sulfhydryls in aqueous solution: Mercaptoethanol, cysteamine, and N-acetyl-L-cysteine
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The technique of combined pulse radiolysis/laser photolysis has been used to investigate the disulfide radical anion formation reactions for mercaptoethanol, cysteamine, and N-acetyl-L-cysteine over the pH range 7.0-13.0. The photolysis of the transient radical anions, formed by the one electron oxidation of the sulfhydryl, perturbs the disulfide radical anion/thiyl radical equilibrium, allowing rate constants for thiyl radical reaction with the parent sulfhydryl to be uniquely determined from the absorption bleach and subsequent recovery. These pH-dependent values were combined with measured disulfide radical anion equilibrium constants to calculate first-order disulfide radical anion dissociation rate constants. By computer modeling of established mechanisms for the disulfide radical anion growths, rate constants for the reaction of hydroxyl radicals with individual sulfhydryl species were calculated. These values are contrasted with previously reported values determined by using competition kinetics.
- Mezyk, Stephen P.
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p. 8295 - 8301
(2007/10/03)
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- Cosmetic composition containing DOPA derivatives
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A composition for topical application to human hair or skin contains a chemical analogue of dihydroxyphenyl alanine (DOPA). This chemical analogue can be absorbed by skin or by a hair follicle and metabolised in-vivo, thus leading to the formation of melanin in skin or to the growth of melanin-pigmented hair. Consequently the composition can give controlled skin darkening to mimic sun-induced tanning or can bring about the growth of dar hair in place of the grey or white hair.
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- Cosmestic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamic acid derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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- Hair growth composition containing citric acid esters
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Triesters of citric acid are used for inducing, maintaining or increasing hair growth. Compositions for topical application to mammalian hair or scalp comprise an effective amount of from 1% to 99% by weight of an ester of citric acid having the structure (1): where, R1, R2 and R3 each independently represent a branched or unbranched alkyl, alkenyl, aryl, alkylaryl or arylalkyl group, each said group having from 1 to 18 carbon atoms, R4 represents -H, or a branched or unbranched saturated or unsaturated acyl, alkyl, aryl, alkylaryl or aylalkyl group having from 1 to 18 carbon atoms, in the presence of a cosmetically acceptable vehicle for the citric acid ester and in the absence of solid absorbent for the ester;, said effective amount of said ester being sufficient to increase hair growth in the rat, when said composition is applied topically thereto over a period of no more than three months, by at least 10% more than that obtainable using a control composition from which the said ester has been omitted, in accordance with the Rat Hair Growth Test.
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- Process for reconfiguring keratin fibre
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A process of recofiguring keratin fibre is disclosed. The process includes rolling, winding, curling, looping lapping, folding, twirling, bending, curving, twisting, coiling, twining, entwining or straightening the keratin fibre or leaving the keratin fibre unchanged. A reducing agent is then applied to the keratin fibre to reduce cystine disulfide linkages and other susceptible linkages in the keratin fibre. An oxidizing agent is applied to the keratin fibre having the reducing agent, to set cystine disulfide linkages in the keratin fibre. The reducing agent and the oxidizing agent are then removed from the keratin fibre by rinsing the keratin fibre.
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from N-acylated amino-acids, in which the acyl group has from 2 to 20 carbon atoms, together with a cosmetically acceptable vehicle for the hair growth promoter.
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- Method of preparing N-acylated mercapto-alpha-amino acids
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N-acylated mercapto-α-amino acids of the general formula STR1 are prepared by reacting a nitrile of the general formula at a temperature between 0° C. and 100° C. in water or in a mixture of water and an organic solvent which is at least partially miscible with water, in the presence of a base with a mercapto-α-amino acid of the general formula STR2 and subsequently releasing the N-acylated mercapto-α-amino acid of general formula (I) with an acid. Mercapto-α-amino acids can be selectively acylated on the amino group in this manner in a relatively simple manner.
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- Chemical Reactions of Omeprazole and Omeprazole Analogues. IV. Reactions of Compounds of the Omeprazole System with 2-Mercaptoethanol
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When omeprazole, 5-methoxy-2-(4-methoxy-3,5-dimethyl-2-pyridinylmethylsulfinyl)-1H-benzimidazole, is dissolved in dilute HCl various reaction products are obtained.The addition of 2-mercaptoethanol greatly simplifies the complexity of these reactions.The reactions between 2-mercaptoethanol and some of the degradation products have been studied in detail.
- Braendstroem, Arne,Lindberg, Per,Bergman, Nils-Ake,Tekenbergs-Hjelte, Lija,Ohlson, Kristina
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p. 577 - 586
(2007/10/02)
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- Formation of Thiocarbonyl Compounds in the Reaction of Ebselen Oxide with Thiols
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Reaction of α-toluenethiol with Ebselen oxide, 2, affords dibenzyl disulfide and seleno sulfide 5, R = PhCH2.In the course of this reaction, thiobenzaldehyde is formed and can be trapped with cyclopentadiene in 90percent yield.Reaction of 2-propene-1-thiol with 2 afforded thioacrolein dimer in 69percent yield and seleno sulfide 5, R = CH2-CH=CH2.Trapping, stereochemical, and isotopic exchange studies were used to determine if in the reaction of 2 with 1-heptanethiol, cyclohexanethiol, and N-acetyl-D,L-cysteine thiocarbonyl compounds heptanethial, cyclohexanethione, and 2-acetamino-3-thioxopropanoic acid (α-thioformyl-N-acetylglycine), respectively, are also formed.These studies showed that free thiocarbonyl compounds are not formed in these reactions.
- Glass, Richard S.,Farooqui, Firdous,Sabahi, Mahmood,Ehler, Kenneth W.
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p. 1092 - 1097
(2007/10/02)
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- Fluorescent and Nonfluorescent Aryl Vinyl Sulfones - Reagents Suitable for Protection and Detection of Thiol Functions
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The rate of the addition of primary, secondary, and tertiary thiols to aryl/alkyl vinyl sulfones 1 and 4-7 is investigated by competing reactions and by kinetics.The obtained acid stable 2-(alkyl-/arylthio)ethyl sulfones are cleaved by bases to give the starting material by rates corresponding to the rates of addition.Therefore, selective introduction and selective elimination of different (arylsulfonyl)ethyl protective groups in the same molecule is possible by using different kinetic steering factors. - Application of the fluorescent vinyl sulfones 5, 10, and 11 opens new fields for analysis and synthesis.SH-selective vinyl sulfones and thiophosphinic acid cyanides are "orthogonal" protective groups.
- Horner, Leopold,Lindel, Hans
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- Thiolic derivatives of erythromycin having therapeutic activity, and pharmaceutical compositions containing them
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The thiolic salts of erythromycin and of the propionic ester of erythromycin with thenoyl alpha-mercaptopropionylglycine find therapeutical use in the cases in which erythromycin or its propionic ester are used and are generally endowed with very low toxicity and high hematic levels.
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