36 results about "Methyllysine" patented technology

The invention provides, in a general sense, a new labeling strategy employing compounds that are are N2S2 chelates conjugated to a targeting ligand, wherein the targeting ligand is a disease cell cycle targeting compound, a tumor angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, amifostine, angiostatin, monoclonal antibody C225, monoclonal antibody CD31, monoclonal antibody CD40, capecitabine, a COX-2 inhibitor, deoxycytidine, fullerene, herceptin, human serum albumin, lactose, leuteinizing hormone, pyridoxal, quinazoline, thalidomide, transferrin, or trimethyl lysine. The present invention also pertains to kits employing the compounds of interest, and methods of assessing the pharmacology of an agent of interest using the present compounds.

The present invention provides reagents and methods for the introduction of analogues of methyl or acetyl lysine into histone proteins.

The invention discloses a method for the clean production of N-trimethyllysine and method of application, wherein the production method consists of screening and protecting alpha-amino with metallic ions, carrying out epsilon-amino reaction between dimethyl carbonate, an environment-friendly type methylating reagent with lysine, obtaining quaternized lysine derivative (N-trimethyllysine metallic complex), finally de-screening the metallic ions with amino carboxyl chelating agent, then isolating and purifying with ion exchange process so as to obtain medicinal grade of N-trimethyllysine, which can be used as the raw material for medicament for preventing or treating high blood pressure, lowering blood fat, maintaining blood vessel, or as food, health product additives.

The invention relates to methods for preparing and using laminine and pharmaceutically acceptable salts thereof. L-lysine is used an initiative material, and the method comprises the following steps of: protecting alpha-amino groups and carboxyl with metallic salts under an alkaline condition to form a chelate complex; performing separation and purification to obtain the chelate complex with the purity of 99 to 100 percent, and performing methylation on the chelate complex on epsilon-amino groups under the action of a phase transfer catalyst with a methylating agent to generate trimethyl lysine salts; removing metallic ions with a precipitator or chelating agent to obtain crude laminine and crude pharmaceutically acceptable salts thereof; and re-crystallizing the crude laminine and the crude pharmaceutically acceptable salts thereof with a solvent to obtain the medicinal laminine and the pharmaceutically acceptable salts thereof. The methylation of the separated and purified L-lysine metallic ion chelate complex and the phase transfer catalyst are simultaneously adopted, so the method remarkably reduces the generation of monomethyl substances, dimethyl substances and other byproducts, improves the yield and achieves the product purity of over 98.5 percent (HPLC).

A pharmaceutical composition comprising a peptide derivative or its pharmaceutical equivalent salt having a general formula, R1N═C(R2)-AA1-AA2-AA3-AA4-Y, in which R1 is such as a hydrogen, R2 is such as a methyl group, Y is such as a methylamino group, AA1 is such as a tyrosine group, AA2 is such as a D-arginine group, AA3 is such as a phenylalanine group, and AA4 is such as a N-methyllysine group has analgesic activity against a variety of pains on both subcutaneous and oral administration.

The invention discloses a carboxymethyl lysine fluorescence imprinting material and a preparing method and application thereof .According to the preparing method, thin layer nano material graphene is used as a carrier, a fluorescence nano material namely quantum dots excellent in optical performance is used as a response element, a molecularly imprinting polymer high in selectivity and specificity is used as a recognition element, an efficient, portable, fast and sensitive molecularly imprinting fluorescence sensing system is set up, carboxymethyl lysine is used as template molecules, 3-aminopropyl triethoxy silane is used as a functional monomer, tetraethoxy-silicane is used as a crosslinking agent, and ammonia water is used as a catalyst .The surface molecularly imprinting material based on graphene and quantum dots is prepared through a reversed-phase microemulsion synthesis method, and carboxymethyl lysine residues can be detected from food fast and easily .

The invention discloses a cleaning manufacturing method of high-purity laminine, which is characterized by the following: adopting lysine as raw material; reacting lysine with metal salt under alkaline condition (pH =7-11) to do alpha-amino shelter reaction to generate intermediate product; reacting with methylating agent to produce quaternised lysine derivant on the yimxilong-amino; generating metal ionic demasking reaction with complexing agent to obtain rough product of N-trimethyl lysine; adsorbing through cationic resin exchange column; washing; purifying to obtain the product; making ammonia as adjuster of pH value.

The invention discloses a detecting method of carboxymethyl lysine (CML). The method is characterized by measuring the content of the CML in food adopting high performance liquid chromatography-tandem mass spectrometry in combination with an HILIC (Hydrophilic Interaction Liquid Chromatography) column for strong-polarity CML separation under a higher organic phase proportion. Crushed food passes through an MCX (Mixed-Mode Cation-Exchange) small column for being extracted and purified after being reduced by sodium borohydride and hydrolyzed by hydrochloric acid; sample liquor is subjected to gradient elution in the HILIC column by taking methanol-water (containing 2 mM ammonium acetate and 0.1% formic acid) as a mobile phase, so that CML is separated from a sample substrate; tandem mass spectrum analysis is carried out by using an electrospray ion source, positive ion scanning and a multi-reaction monitoring mode; quantitative analysis is carried out by using D4-CML as an internal standard substance, wherein analysis time is 12 minutes, and CML has an absorption peak at the retention time of 3.47 minutes. The detecting method disclosed by the invention is high in sensitivity, high in accuracy and good in precision, does not need to carry out derivatization onto samples, simplifies sample pre-treatment, shortens detecting time and saves detecting cost.

The invention discloses application of an antigen containing 6-N-methyllysine residue in preparation of reagents or kits for auxiliary diagnosis of systemic lupus erythematosus. Experiments of the invention prove that human IgM can identify 6-N-methyllysine, and can be combined with arbitrary peptide or protein containing 6-N-methyllysine residue, 6-N-methyllysine has an inhibitory effect on IgM identifying 6-N-methyllysine, but non-methylation modified lysine has no inhibitory effect, most healthy people have a high level of the IgM antibody, and the level of the IgM antibody is significantly reduced in patients with systemic lupus erythematosus. The antigen containing 6-N-methyllysine residue can be used for preparation of reagents or kits for auxiliary diagnosis or screening of systemic lupus erythematosus.

The present invention provides compounds, or derivatives or prodrugs thereof, that comprise a methyllysine mimic, and an α-ketoglutarate mimic that are attached through a linker and methods for using and producing the same. In some embodiments, compounds of the invention are of the formula: M-L-K, or a derivative or a prodrug thereof, wherein M is a methyllysine mimic, L is a linker, and K is an α-ketoglutarate mimic.

Antibodies capable of recognizing many types of proteins having methyllysine residues are established by immunizing an animal with a chemically methylated protein other than histone and subsequent screening or the like depending on the reactivity to a protein obtained by chemically methylating a protein other than the protein used in the immunization. A process for producing such an antibody is also established. These antibodies are useful in searching for and studying various methylated proteins and are particularly useful in regulating the functions of biological molecules wherein the methylation of a lysine residue plays an important role, and in diagnosing a disease by detecting a methyllysine-containing protein.

The present invention provides reagents and methods for the introduction of analogues of methyl or acetyl lysine into histone proteins.

The present invention relates to a method for producing a polypeptide. The method includes labeling a molecular probe precursor represented by an amino acid sequence of the formula (1) using a labeling compound capable of labeling a lysine or lysine derivative:(1)Y1-Leu-Ser-Xaa12-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Xaa27-Asn-Gly-Y2where Y1 represents an amino acid sequence represented by the formula (2) or the amino acid sequence represented by the formula (2) with 1 to 8 amino acids from the N-terminus being deleted, Xaa12 represents a lysine or lysine derivative, Xaa27 represents a basic amino acid having no functional group at its side chain that reacts with the labeling compound or represents methyl lysine or acetylated lysine, and Y2 represents an amino acid sequence represented by the formula (3) or the amino acid sequence represented by the formula (3) with 1 to 9 amino acids from the C-terminus being deleted:(2)His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp(3)Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser

This invention relates to a method of immobilizing biocatalysts including protein and cells by co-precipitation with silicate or organosilicate matrices through the action of an organic template molecule. The organic template molecule is in general a polyamine such as polyethylenimine (PEI), or polypeptide compound bearing at least two or three basic residues selected from the group consisting of lysine, arginine, histidine, proline, hydroxyproline, N-methylhistidine, ornithine, taurine, δ-hydroxylysine, and δ-hydroxy-ω-N,N,N trimethyllysine. The invention is also directed to a silica biocomposite comprising co-precipitates of active biocatalysts, silica or organosilicates, and an N-containing organic template molecule. Such silica biocomposites are useful in biocatalysis, and other applications requiring an immobilized biocatalyst. Preferred biocatalysts for this invention are enzymes and whole cells.

The present invention provides compounds, or derivatives or prodrugs thereof, that comprise a methyllysine mimic, and an α-ketoglutarate mimic that are attached through a linker and methods for using and producing the same. In some embodiments, compounds of the invention are of the formula: M-L-K, or a derivative or a prodrug thereof, wherein M is a methyllysine mimic, L is a linker, and K is an α-ketoglutarate mimic.

The invention provides, in a general sense, a new labeling strategy employing compounds that are N2S2 chelates conjugated to a targeting ligand, wherein the targeting ligand is a disease cell cycle targeting compound, a tumor angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, amifostine, angiostatin, monoclonal antibody C225, monoclonal antibody CD31, monoclonal antibody CD40, capecitabine, a COX-2 inhibitor, deoxycytidine, fullerene, herceptin, human serum albumin, lactose, leuteinizing hormone, pyridoxal, quinazoline, thalidomide, transferrin, or trimethyl lysine. The present invention also pertains to kits employing the compounds of interest, and methods of assessing the pharmacology of an agent of interest using the present compounds.

The present invention relates to systems, kits, and methods for identifying subjects with increased levels of N6-trimethyl-lysine (TML) or the combination of TML and trimethylamine-n-oxide (TMAO), as well as methods of determining risk of disease (e.g., kidney disease or heart failure) based on such levels. In certain embodiments, subjects with elevated TML, or TML and TMAO are treated with a therapeutic (e.g., one that inhibits the TMA / FMO3 / TMAO pathway).

The invention discloses a method for detecting AGEs (Advanced Glycation End Products) and application. The method comprises the following steps: firstly preparing a glassy carbon electrode modified bygraphene-chitosan / N(epsilon)carboxymethyl lysine, and then realizing multi-residue detection on five AGEs comprising the N(epsilon)carboxymethyl lysine, N(epsilon)carboxyethyl lysine, pentosidine, pyruvaldehyde imidazolinone and argpyrimidine by combining an indirect competition method on the basis of a principle that cross immunoreaction can be generated by a pentosidine monoclonal antibody andmultiple AGEs. According to the method for detecting the AGEs, disclosed by the invention, the problem that a current AGEs detecting method just can be used for detecting a single substance is solved,higher sensitivity (of which the detecting limit is 0.06 to 0.1 ng / mL) and wider linear range (0.1 to 1000 ng / mL) are obtained, the operation is simple, the cost is lower, the demands on clinical AGEs detection of a human body can be completely fitted, and important practical application value is obtained.

The invention provides a preparation method of N omega-methyl-lysine, which comprises the following steps that: cupric salt is added into sodium hydroxide solution of L-lysine, tosyl chloride solution which is dissolved in organic solvent is added in under the stirring state, and then sodium hydroxide solution is added into to have stirring reaction; after the reaction, iodomethane is added in; after the reaction is ended, the pH value is regulated to be 3 to 5 after cooling, and B is prepared after treatment; the chemical compound B is heated to have reflux reaction for 1 to 4h after being mixed with hydrobromide, and then is cooled, separated and purified, the pH value is regulated to be 3 to 6, and C is prepared after treatment; and the acetone solution of the chemical compound C is mixed with sodium bicarbonate aqueous solution, 8- hydroxyquinoline is added in, and the N omega-methyl-lysine is prepared after treatment. The preparation method of N omega-methyl-lysine optimizes the process of a metal ion complexation method, simplifies the step of protecting Alpha-amino with benzoyl in a traditional synthesis method, simplifies the separation and purification processes and realizes the industrial production of single lysine methylation, and an intermediate body does not need to be separated and purified.

There is provided a composition comprising: A) serine, glycine, betaine, N- acetylglycine, N-acetylserine, dimethylglycine, sarcosine and / or phosphoserine; B) N-acetyl cysteine, cysteine and / or cystine; C) optionally carnitine, deoxycarnitine, gamma-butyrobetaine, 4- trimethylammoniobutanal, 3-hydroxy-N6,N6,N6-trimethyl-L-lysine, N6,N6,N6-trimethyl-L-lysine and / or lysine; and D) nicotinamide riboside, quinolinate, deamino-NAD+, nicotinate D-ribonucleotide, nicotinamide D- ribonucleotide, nicotinate D-ribonucleoside,nicotinamide and / or nicotinate, wherein the molar ratio of A) to D) is between250:1 and 1.5:1 and the molar ratio of A) to B) is between 16:1 and 1:4. The composition may be used in a method of treatment of a medical condition selected from the group consisting of non-alcoholicfatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), type 2 diabetes, obesity, insulin resistance and dyslipidemia.

The invention relates to A method of making a polypeptide comprising at least one Nε-methyl-lysine at a specific site in said polypeptide, said method comprising (a) genetically directing the incorporation of R—Nε-methyl-lysine into said polypeptide, wherein R comprises an auxiliary group; and (b) catalysing the removal of R from the polypeptide of (a). In particular the invention relates to such a method wherein genetically directing the incorporation of R—Nε-methyl-lysine into said polypeptide comprises arranging for the translation of a RNA encoding said polypeptide, wherein said RNA comprises an amber codon, and wherein said translation is carried out in the presence of an amber tRNA charged with R—Nε-methyl-lysine.

The invention belongs to the field of medical chemistry, and particularly relates to a preparation method of N-Fmoc-N '-Boc-alpha-methyl-L-lysine (hereinafter referred to as a compound 1). Aiming at the defects of tedious steps, high byproduct content, low yield and poor production safety in the existing preparation method of N-Fmoc-N '-Boc-alpha-methyl-L-lysine, the invention provides a new synthesis route and preparation method: 1, 4-diiodobutane is used as a starting material and is subjected to nucleophilic substitution with a compound 3 to generate a compound 4; the method comprises the following steps: reacting a compound 1 with a compound 2 to generate a compound 5 under the action of KHMDS, removing chiral prothetic groups and protecting groups through hydrogenation reduction, and protecting with Fmoc to obtain a compound 1, and the total yield is 52.6%. According to the route, N-Fmoc-N '-Boc-alpha-methyl-L-lysine is obtained through four-step convergent synthesis, and the production period is greatly shortened. The method has the advantages of simple production process steps, high yield, few byproducts, high process safety, good stability and environmental protection.

Provided is a microorganism that belongs to Enterobacteriacae and a method of producing L-carnitine using the same. The microorganism includes polynucleotide encoding activity of S-adenosylmethionine-6-N-iysine KDa methyltransferase from Neurospora crassa, polynucleotide encoding activity of 6-N-trimethyllysine hydroxylase, polynucleotide encoding activity of 3-hydroxy-6-N-trimethyllysine aldolase, and polynucleotide encoding activity of γ-trimethylaminoaldehyde dehydrogenase and y-butyrobetaine hydroxylase.

The invention discloses application of an antigen containing 6-N-methyllysine residue in preparation of reagents or kits for auxiliary diagnosis of systemic lupus erythematosus. Experiments of the invention prove that human IgM can identify 6-N-methyllysine, and can be combined with arbitrary peptide or protein containing 6-N-methyllysine residue, 6-N-methyllysine has an inhibitory effect on IgM identifying 6-N-methyllysine, but non-methylation modified lysine has no inhibitory effect, most healthy people have a high level of the IgM antibody, and the level of the IgM antibody is significantly reduced in patients with systemic lupus erythematosus. The antigen containing 6-N-methyllysine residue can be used for preparation of reagents or kits for auxiliary diagnosis or screening of systemic lupus erythematosus.

The invention relates to methods for preparing and using laminine and pharmaceutically acceptable salts thereof. L-lysine is used an initiative material, and the method comprises the following steps of: protecting alpha-amino groups and carboxyl with metallic salts under an alkaline condition to form a chelate complex; performing separation and purification to obtain the chelate complex with the purity of 99 to 100 percent, and performing methylation on the chelate complex on epsilon-amino groups under the action of a phase transfer catalyst with a methylating agent to generate trimethyl lysine salts; removing metallic ions with a precipitator or chelating agent to obtain crude laminine and crude pharmaceutically acceptable salts thereof; and re-crystallizing the crude laminine and the crude pharmaceutically acceptable salts thereof with a solvent to obtain the medicinal laminine and the pharmaceutically acceptable salts thereof. The methylation of the separated and purified L-lysine metallic ion chelate complex and the phase transfer catalyst are simultaneously adopted, so the method remarkably reduces the generation of monomethyl substances, dimethyl substances and other byproducts, improves the yield and achieves the product purity of over 98.5 percent (HPLC).

The present invention provides a method for industrially producing an optically active lysine derivative useful as a pharmaceutical intermediate. More particularly, the present invention provides a production method including protecting an amino group or an amino group and carboxyl group of optically active 2-amino-6-methyl-6-nitroheptanoic acid with a protecting group, reducing a nitro group to synthesize a 6,6-dimethyl lysine derivative and reacting the 6,6-dimethyl lysine derivative with an acetic acid derivative.

Provided is a microorganism that belongs to Enterobacteriacae and a method of producing L-carnitine using the same. The microorganism includes polynucleotide encoding activity of S-adenosylmethionine-6-N-iysine methyltransferase from Neurospora crassa, polynucleotide encoding activity of 6-N-trimethyllysine hydroxylase, polynucleotide encoding activity of 3-hydroxy-6-N-trimethyllysine aldolase, and polynucleotide encoding activity of γ-trimethylaminoaldehyde dehydrogenase and y-butyrobetaine hydroxylase.

The invention relates to A method of making a polypeptide comprising at least one Nε-methyl-lysine at a specific site in said polypeptide, said method comprising (a) genetically directing the incorporation of R—Nε-methyl-lysine into said polypeptide, wherein R comprises an auxiliary group; and (b) catalysing the removal of R from the polypeptide of (a). In particular the invention relates to such a method wherein genetically directing the incorporation of R—Nε-methyl-lysine into said polypeptide comprises arranging for the translation of a RNA encoding said polypeptide, wherein said RNA comprises an amber codon, and wherein said translation is carried out in the presence of an amber tRNA charged with R—Nε-methyl-lysine.

The invention provides a quantitative analysis method and a kit for one-time detection of multiple intestinal microbial metabolites for the first time. The kit is composed of a reference substance, a quality control substance, an isotope internal standard extracting solution, a reinforcing agent, an extracting solvent, a mobile phase additive A, a mobile phase additive B, a 96-hole reaction plate, a 96-hole filter plate and a specification. The kit can be used for simultaneously detecting acetyl L-carnitine, betaine aldehyde, betaine, choline chloride, crotonbetaine hydrochloride, gamma-butyrobetaine, L-carnitine, trimethylamine hydrochloride, trimethyl lysine and trimethylamine oxide, the consumed time is short, and the detection efficiency is improved.