281 results about "D-amino acid" patented technology

The present invention provides compounds of the formula X—R1-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)—R3(Y)—NR4R5; or R1(X)-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)—R3(Y)—NR4R5, in which X is a hard acid cation chelator, a soft acid cation chelator or Ac—, R1, R2 and R3 are independently selected from a covalent bond or one or more D-amino acids that can be the same or different, Y is a hard acid cation chelator, a soft acid cation chelator or absent, Z is a hard acid cation chelator, a soft acid cation chelator or absent, and A and B are haptens or hard acid cation chelators and can be the same or different, and R4 and R5 are independently selected from the group consisting of hard acid cation chelators, soft acid cation chelators, enzymes, therapeutic agents, diagnostic agents and H. The present invention also provides methods of using these compounds and kits containing the compounds.

The invention discloses an enzyme-chemocatalysis racemization removing preparation method for L-glufosinate-ammonium. According to the method, a one-pot reaction manner is adopted, under the molecular oxygen, immobilization D-amino acid oxidase catalyzes D-enantiomer in an enantioselectivity mode into 2-imino-4-(hydroxy methyl phosphonyl) butyric acid in a dehydrogenation mode, and palladium-ammonium formate catalyzes 2-imino -4-(hydroxy methyl phosphonyl) butyric acid into DL-glufosinate-ammonium in an in-situ reduction mode. Hydrogen peroxide produced in the process is efficiently decomposed into water and oxygen through catalase. Complete reacemization removing of DL-glufosinate-ammonium and efficient preparing of L-glufosinate-ammonium are achieved through biological oxidation-chemical reduction circulation. The method has the advantages that the process is simple, cost is low, environmental friendliness is achieved, and energy is saved. High-concentration DL-glufosinate-ammonium can be converted into L-glufosinate-ammonium. The yield is 90%, the optical purity of the product is 99%, and the method is suitable for industrial production of L-glufosinate-ammonium.

A sustained-release preparation which comprises a physiologically active peptide of general formulawherein X represents an acyl group;R1, R2 and R4 each represents an aromatic cyclic group;R3 represents a D-amino acid residue or a group of the formulawherein R3′ is a heterocyclic group;R5 represents a group of the formula —(CH2)n—R5′ wherein n is 2 or 3, and R5′ is an amino group which may optionally be substituted, an aromatic cyclic group or an O-glycosyl group;R6 represents a group of the formula —(CH2)n—R6′ wherein n is 2 or 3, and R6′ is an amino group which may optionally be substituted;R7 represents a D-amino acid residue or an azaglycyl residue; andQ represents hydrogen or a lower alkyl group, or a salt thereof and a biodegradable polymer having a terminal carboxyl group.The sustained-release preparation shows a constant release of the peptide over a long time and is substantially free from an initial burst.

The invention comprises a substrate for detection of micro-organisms, wherein said substrate comprises a set of molecular markers linked, optionally with linker molecules or moeieties, to a di-, or tripeptide consisting of amino acids X1 and X2, or X1, X2 and X3, in which one of them, for example X1, is a D-amino acid and the others, for example X2 and X3, may be any D- or L-amino acid. Said substrate preferably is used for the detection of Bacillus anthracis. Alternatively, the invention is directed to a substrate for detection of micro-organisms, more specifically P. aeruginosa, wherein said substrate comprises a set of molecular markers linked, optionally with linker molecules or moeities to a tri- tetra or pentapeptide consisting of glycine amino acids. The invention further comprises methods for detection of micro-organisms, specifically Bacillus anthracis and Pseudomonas aeruginosa, with the substrates of the invention and use of the substrate(s) in such a method.

The present invention provides compositions and methods and for increasing the bioavailability of therapeutic agents in a subject. The compositions include at least one alkyl glycoside and at least one therapeutic agent, wherein the alkylglycoside has an alkyl chain length from about 10 to about 16 carbon atoms. In various aspects, the invention provides compositions and methods for oral delivery of peptides containing non-naturally occurring structures including D-amino acids and / or chain cyclization.

The invention discloses a method for preparing L-phosphinothricin through deracemization and by a biological enzyme method. According to the method, the L-phosphinothricin is obtained by taking D,L-phosphinothricin as a raw material and through catalysis by an enzyme catalysis system, and the enzyme catalysis system consists of D-amino acid oxidase, amino acid dehydrogenase and coenzyme regeneration systems. By the method, racemized D,L-phosphinothricin serves as the raw material, the D-phosphinothricin is oxidized into 2-carbonyl-4-(hydroxymethylphosphonyl)-butyric acid by the D-amino acid oxidase, and the L-phosphinothricin does not take part in the reaction and is completely retained; but the 2-carbonyl-4-(hydroxymethylphosphonyl)-butyric acid is catalytically reduced into the L-phosphinothricin by the amino acid dehydrogenase, so that in-situ deracemization of the D,L-phosphinothricin is realized, the obtained L-phosphinothricin does not contain other side products, the total yield of the products is more than or equal to 99 percent, and the optical purify can exceed 99 percent.

The invention discloses a synthetic polypeptide, the amino acid sequence of the synthetic polypeptide meets the following general formula: Ac-X0-(X1-X2-X3-X4)n-NH2, wherein Ac is an acetylized N-terminal; X0 is an L-amino acid, and the type of the amino acid is Ala, Val or Gly; X1, X2, X3 and X4 are all L-amino acids or D-amino acids, X1 is a positive charge amino acid Arg, Lys or His, X3 is a negative charge amino acid Asp or Glu, and X2 and X4 are amino acids Ala, Val or Gly without charge; X1-X2-X3-X4 is a repeated sequence; and n is repeated times of amino acid arrangement in the sequence, and is equal to 2, 3 and 4. The polypeptide has the characteristics of forming a nano fiber screen through self-assembly, and can form a gel-like fiber screen in the particle environment in vitro or in vivo for hemostasis or wound nursing.

The invention belongs to the field of medical chemical antiviral effects, and relates to an acyclic nucleoside phosphamide D-amino-acid ester derivative, a preparation method of derivative salt and an application of the derivative to the antiviral effects. The invention further provides a compound comprising the derivative, a stereoisomer of the derivative, pharmaceutically acceptable salt, a hydrate, a solvate or crystal and drug combination and an application of the compound or combination to treatment and / or prevention of Aids and hepatitis B virus infection. The in vivo activity of the compound is remarkably superior to that of a pro-drug of acyclic nucleoside phosphamide L-amino-acid ester, and the compound has obvious clinical application values.

This invention relates to compounds, compositions, and methods useful for modulating G72 and / or D-amino acid oxidase (DAAO) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of G72 and / or D-amino acid oxidase (DAAO) gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of G72 and / or DAAO genes. The small nucleic acid molecules are useful in the treatment of schizophrenia and any other condition that responds to modulation of G72 and / or DAAO expression or activity.

Methods and systems for discovering drug candidates are disclosed. Methods and systems can include generating libraries of potential drug candidates (e.g., libraries of peptides) that can be screened to identify sub-libraries of potential drug candidates (e.g., sub-libraries of peptides) having selected pharmacological properties. Methods of making and using peptide libraries are also provided. D-amino acid chlorotoxins and D-amino acid chlorotoxin variants are also provided.

The present invention provides a pharmaceutical composition for oral administration comprising a D-amino acid combined with an antioxidant selected from the group consisting of vitamin E, vitamin C, a glutathione or a precursor thereof.

The invention relates to recombinant microorganisms which, in comparison to the starting organism, have a higher concentration or activity of a D-amino acid oxidase, of an L-amino acid dehydrogenase, of an NADH cosubstrate regenerating enzyme and, if necessary, of a catalase. The invention also includes methods for preparing L-amino acids from D-amino acids using of these microorganisms.

A self-assembling peptide constituted by D-amino acid is named as d-RAD16 and has an amino acid sequence represented by SEQ ID NO.1 in a sequence list. Test shows that hydrogel formed by the self-assembling peptide can be used for preparing a moisture keeping and water locking agent, and has the function of stopping bleeding rapidly for wound, so that the hydrogel can be used for preparing a hemostatic drug suiting clinical application by adding a pharmaceutically acceptable carrier or excipient. Nanofiber scaffold formed by the self-assembling peptide supports the growth of various cells and can be used as the substrate material for 3D cell culture. The substrate material for 3D cell culture can simulate the in-vivo environment to support the 3D growth of cells in the substrate, thereby providing a cell 3D culture drug screening mode capable of simulating the in-vivo environment and improving the success rate for the development of new drugs.

Process for producing the enzyme D-amino acid oxydase of Rhodotorula gracilis in host cells. The process for the expression of the enzyme comprises isolating the complementary DNA corresponding to the messager RNA of the gene which codes for the D-amino acid oxydase of any strain of Rhodotorula gracillis producing said enzyme; fusing the fragment of DNA which codes for D-amino acid oxydase of Rhodotorula gracillis with a DNA sequence which contains a site of union to the ribosome and a high efficiency promoter sequence for the express of genes in host cells; inserting the DNA fragment into a plasmid appropriate for the host cell; cultivating the host cells transformed with said plasmid; and collecting the enzyme.

The invention discloses a D-amino acid oxidase mutant and application thereof. The mutant is obtained by carrying out single mutagenesis or multiple mutagenesis on a 52nd site, a 54th site, a 58th site, a 213rd site and a 335th site of amino acid with an amino acid sequence shown in SEQ ID NO.1, wherein glycine at the 52nd site is mutated into leucine, asparagine at the 54th site is mutated into valine, phenylalanine at the 58th site is mutated into glutamine, methionine at the 213rd site is mutated into serine, and serine at the 335th site is mutated into glycine. According to the D-amino acid oxidase mutant and the application thereof, a D-amino acid oxidase gene with an amino acid sequence as shown in SEQ ID NO.2 is mutated by utilizing a site-saturation mutagenesis technology, so thatthe enzyme activity and the product conversion rate are far higher than those of a wild type, and therefore the product yield in a 4-(hydroxymethylphosphoryl)-2-carbonyl-butanoic acid production process is increased.

The present invention provides methods for the screening and identification of agents from a large library of molecular structures that can alter the cleavage of amyloid precursor protein (AP). Agents identified by the methods of the present invention that modify the cleavage of APP can be used in the treatment and prevention of Alzheimer's disease. The methods select for and identify effector agents that bind to APP causing a structural change in the structure of APP in such a way that the efficiency of the cleavage of a secretase is modulated. Further, the methods are carried out in an in vivo system that provides for physiological conditions similar or identical to conditions for APP processing. Agents can be selected for their ability to cause a decrease in the amount of B-secretase or β-secretase cleavage of APP, or for an increase in a-secretase cleavage of APP. The agents can be, particularly peptide agents, can be converted into a peptidominetic, an isosteric replacement compound, a D-amino acid analog, or non-peptidyl compound for treating Alzheimer's disease or any other amyloid related or prion related disease. The agents or derivatives thereof can be formulated for intravenous, parenteral, topical, sustained release, intranasal, or inhalation use.

The invention relates to a novel nucleoside phosphate / phosphonate prodrug containing non-naturalD-amino acid ester, a preparation method and a medical purpose thereof. The novel nucleoside phosphate / phosphonate prodrug containing a substituted benzyl group is a compound shown in a formula (I) or a formula (II) or its isomer or medicinal salt, which can be used as the prodrug of various nucleoside analogues such as acyclic nucleoside, carbocyclic nucleoside, and furan ring nucleoside, biological activity of the nucleoside compound can be enhanced, so that the derivative can be used for treating virus infection and cancer.

The invention discloses fructose amino acid oxidase which has an amino acid sequence shown as SEQID.No.1 (sequence identifier number 1) or has above 80% homology with the amino acid sequence. One or more amino acid residues in corresponding positions of amino acid selected from (a) to (f) are substituted. The obtained fructose amino acid oxidase has higher thermostability: (a) 59-site glutamic acid, (b) 98-site glutamic acid, (c) 225-site glycine, (d) 277-site lysine, (e) 283-site glutamic acid and (f) 355-site aspartic acid. The invention further discloses a preparation method of the oxidase and a kit comprising the oxidase and used for determining glycatedalbumin. The kit has higher thermostability and can accurately determine the glycatedalbumin.

The invention discloses a mutant zymoprotein of D-amino acid oxidase and preparation method of the mutant zymoprotein. The preparation method comprises the following steps: according to homologous sequence comparison result, respectively performing mutation on 115, 119 and 286 sites of D-amino acid oxidase in primary Arthrobacterprotophormiae (DSM15035) through site-specific mutagenesis technology to construct three-site mutation expression vector Pet-e115A / N119D / T286A; and carrying out prokaryotic expression and purification to obtain zymoprotein. An apparent secondary speed constant Kcat / Km of the obtained mutant protein to substrate D-Met is 1.39*10 to the power of 5s-1.M-1, is 5.03 times of wild type DAAO (D amino acid oxidase), and is 55.96 times of pKDAAO protein of pig kidney source. The detection efficiency of partial D-amino acid can be improved, and the good application value is realized.

This invention provides an ADNF polypeptide comprising an active core site, the active core site comprising at least one D-amino acid. The invention also provides a pharmaceutical composition comprising an ADNF polypeptide comprising an active core site, the active core site comprising at least one D-amino acid. In particular, the pharmaceutical composition of the invention is orally active. The invention further provides methods for reducing neuronal cell death, methods for reducing oxidative stress, and methods for reducing a condition associated with fetal alcohol syndrome using the ADNF polypeptides and the pharmaceutical compositions of the invention.

The invention discloses a method for preparing L-glufosinate-ammonium through microorganism catalysis and deracemization. According to the method, DL-glufosinate-ammonium is used as a raw material, D-amino acid oxidase in lysinibacillus xylanilyticus XX-2 whole cells catalyzes D-glufosinate-ammonium to be subjected to oxidative deamination to obtain 4-(hydroxymethylphosphinyl)-2-oxobutanoic, and L-glufosinate-ammonium is reserved. The amino acid dehydrogenase co-expressed in cells catalyzes the 4-(hydroxymethylphosphinyl)-2-oxobutanoic to be subjected to in-situ reduction and ammoniation to obtain the L-glufosinate-ammonium, so that complete deracemization of the DL-glufosinate-ammonium is realized. The prepared L-glufosinate-ammonium does not have any other by-products, the total yield isgreater than 70%, and the optical purity is greater than 99%.

This invention provides an ADNF polypeptide comprising an active core site, the active core site comprising at least one D-amino acid. The invention also provides a pharmaceutical composition comprising an ADNF polypeptide comprising an active core site, the active core site comprising at least one D-amino acid. In particular, the pharmaceutical composition of the invention is orally active. The invention further provides methods for reducing neuronal cell death, methods for reducing oxidative stress, and methods for reducing a condition associated with fetal alcohol syndrome using the ADNF polypeptides and the pharmaceutical compositions of the invention.

Non-hemolytic cytolytic agents selected from peptides, complexes of bundled peptides, mixtures of peptides or random peptide copolymers have a selected cytolytic activity manifested in that they have a cytolytic activity on pathogenic cells, being cells which are non-naturally occurring with the body consisting of microbial pathogenic organisms and malignant cells; and are non-hemolytic, having no cytolytic effect on red blood cells. The peptides may be cyclic derivatives of natural peptides such as pardaxin and mellitin and fragments thereof in which L-amino acid residues are replaced by corresponding D-amino acid residues, or are diastereomers of linear peptides composed of varying ratios of at least positively charged amino acid and at least one hydrophobic amino acid, and in which at one of the amino acid residues is a D-amino acid. Pharmaceutical compositions comprising the non-hemolytic cytolytic agents can be used for the treatment of several diseases caused by pathogens including antibacterial, fungal, viral mycoplamsa and protozoan infections and for the treatment of cancer.

This invention discloses a method for preparing D-amino acid. The method comprises: derivatizing DL-amino acids to obtain N-phenylacetyl-DL-amino acids, performing enzyme-catalyzed asymmetric hydrolysis in aqueous solution to obtain N-phenylacetyl-D-amino acid, and performing chemical hydrolysis and crystallization to obtain D-amino acid. The enzyme used is immobilized penicillin acylase, which can be used for more than 100 times. The method has such advantages as high yield and high product optical purity, and is suitable for the majority of DL-amino acids resolution.

The present invention provides a method for synthesizing etelcalcetide or salts thereof, comprising the steps of: (a) synthesizing the D-amino acids in the formula (I) sequentially by Fmoc solid-phase synthesis, using a solid support as a starting material in solid phase peptide synthesis and sequentially synthesizing a D-form amino acid of formula (I) by Fmoc chemistry; deprotecting Fmoc group and acetylating the amino group to obtain a sequence A comprising protecting groups (PG) in the side chain of D-Cys and D-Arg; (b) removing the protecting group in the side-chain of D-Cys of the sequence A to form a sequence B; (c) disulfide formation at D-Cys of the sequence B by (PG)-L-Cys-OH to obtain a sequence C; (d) using a cleavage solution to remove the protecting groups of the sequence C to give etelcalcetide as formula (I). The present invention can shorten the steps and time for preparing Etelcalcetide.

The present invention provides methods and agents for treating subjects who have or are at risk of developing or having cardiovascular disease. Such agents inhibit binding of myeloperoxidase (MPO) to a molecule comprising the MPO binding site of apolipoprotein A-1 (apoA-1) and include a peptide fragment of apoA-1 comprising at least 4 contiguous amino acids in SEQ ID. NO: 2, a modified form of the apo-1 fragment comprising one or more D amino acids, a retro-inverso form of the apoA-1 peptide fragment, an organo-mimetic of the apoA-1 peptide fragment, a peptide-mimetic of the apoA1 peptide fragment, or a nucleic acid encoding the apo A-1 peptide fragment. The present invention also provides methods of identifying or screening test agents for treating subjects having or at risk of having or developing CVD. The method comprises incubating one or more test agents and MPO with a molecule comprising the MPO binding site of apoA-1 under conditions which permit binding of MPO to the MPO binding site and determining whether one or more of the agents inhibit such binding.

The invention belongs to the field of antibacterial preservatives and food fresh-keeping packaging materials and particularly relates to a method for preparing a load D-amino acid / cinnamon essential oil nanofiber antibacterial film and application. By wrapping D-amino acid and cinnamon essential oil with chitosan nano particles, volatilization of the essential oil is reduced, and the essential oil utilization rate is improved. The D-amino acid / cinnamon essential oil / chitosan nano particles are added into an electrostatic spinning solution to prepare the nanofiber antibacterial film, so as to reduce gathering and descending phenomena arising when the chitosan nano particles are directly sprayed on the surface of a food, and then the antibacterial film undergoes auxiliary processing through a cold plasma and then is used for restraining formation of a staphylococcus aureus biological film on a bean product. The method is simple to operate, the biological film is applied to refreshment of soybean products, so growth of pathogenic microorganisms can be effectively restrained, the guarantee period of the products is prolonged, and the method has high market value.

The invention is a method of preparing D-amino acid oxidase, relating to a method of preparing flavo-enzyme D-amino acid oxidase. Concretely, it relates to a method of highly efficiently producing mutational D-amino acid oxidase by constructing recombinant engineering strains. It reconstructs wild D-amino acid oxidase coming from Trigonopsis variablilis by means of gene engineering, fuses a segment of Histag at N end and C end of the wild enzyme, and further implements high-efficiency fast separation of mutational enzyme by affinity chromatography. The expression level of the enzyme in fermentation liquor is 4000IU / mL, higher than that of the wild enzyme, and the recovery ratio of Ni-column affinity chromatography is 50%. The purified enzyme can be used in making high-efficient oxidation conversion of cephalosporin C- to produce glutaryl-7-ACA and be used together with GL-7-ACA to produce 7-ACA.