Abstract: A method for purifying an amino acid from an initial mixture is disclosed, in which the amino acid includes an aromatic ring and has an acidity constant Ka, the method including: a first step of putting the initial mixture into contact with a strong cation resin, at a pH greater than or equal to pKa; and a second elution step with an aqueous solution of eluent having a pH greater than the pH of the first step, giving the possibility of collecting a flow enriched in the amino acid.

Abstract: A method of determining the relative concentrations of enantiomeric forms of a compound in an enantiomeric mixture includes combining the enantiomeric mixture with carbon nanotubes or graphene to form a carbon-enantiomer mixture, exposing the mixture to a monochromatic polarized light, and analyzing reflected polarized light from the mixture using a differential analyzer.

Abstract: This disclosure teaches the novel use of trifluoroacetamide for N-terminal protection. The disclosure also teaches novel compositions and chemical structures associated therewith. These methods and compositions are useful for site-specific methylation of peptide backbone amides, performed, for example, to modulate the pharmacokinetic properties of peptide drugs.

Abstract: Methods for the synthesis of an indole in provided. Methods comprise oxidizing a N-aryl imine in the presence of a palladium-based catalyst, an oxidant, and a solvent.

Abstract: The present invention relates to an improved method for the synthesis of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: Dipeptide analogs comprising a tryptophan (Trp) moiety coupled to a beta-sheet breaker moiety derived from alpha-aminoisobutyric acid (Aib) are disclosed. The dipeptide analogs exhibit an improved performance in inhibiting amyloid fibril formation, as compared to previously described dipeptides. Compositions containing the dipeptide analogs and uses thereof in treating amyloid-associated diseases and disorders are also disclosed.

Abstract: The invention relates to a method for separating off tryptophan from aqueous mixtures of matter, in particular fermentation broths that are already partially processed, using simulated countercurrent chromatography or simulated moving bed (SMB) chromatography, and a device for carrying out the method.

Abstract: The present invention relates to pharmaceutically acceptable crystalline and amorphous salts of D-isoglutamyl-D-tryptophan as well as processes for their manufacture, pharmaceutical compositions comprising them, and their uses in the preparation of pharmaceutical compositions for the treatment of various conditions and/or diseases. In particular, the present invention relates to D-isoglutamyl-D-tryptophan potassium salt (1:1), D-isoglutamyl-D-tryptophan lithium salt (1:1), D-isoglutamyl-D-tryptophan calcium salt (2:1), D-isoglutamyl-D-tryptophan magnesium salt (2:1), and D-isoglutamyl-D-tryptophan organic ammonium salts (1:1).

Abstract: The present invention relates to crystalline forms of the mono-sodium salt of D-isoglutamyl-D-tryptophan, pharmaceutical compositions comprising them, their use in the treatment of various diseases and conditions, and processes for their preparation. In particular, the present invention relates the crystal modification 1 (polymorphic form F) of the mono-sodium salt of D-isoglutamyl-D-tryptophan.

Abstract: The present invention relates to an improved method for the synthesis of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: This invention provides a method of producing a large amount of an ?-form or ?-form of N-pyranosyl-tryptophan having a specified structure and preparing an antibody therefrom. The method comprises a step of allowing a pyranose compound to react with a 3-pyrazyl-indole compound in the presence of a first base to obtain a 1-pyranosyl-3-pyrazyl-indole compound, and a step of treating the 1-pyranosyl-3-pyrazyl-indole compound with an acid, treating the resultant with a hydrogenation catalyst, and further treating the resultant with a second base to synthesize N-pyranosyl-tryptophan, thereby producing an antibody therefrom.

Abstract: Methods and materials for the production of the high intensity sweetener, monatin, in stereoisomerically-pure or stereoisomerically-enriched form are disclosed. For example, methods using stereoisoselective hydrolysis and separation of a monatin-derived lactone ester are disclosed.

Abstract: Methods for preferentially hydrolyzing one stereoisomer of an isoxazoline diester over another, as well as an enzyme for facilitating the preferential hydrolysis are provided. Also provided are methods for providing mixtures of (RR) and (RS) monatin as well as (SS) and (SR) monatin, which methods can include the step of stereoselectively hydrolyzing an isoxazoline diester.

Abstract: A method for making a surfactant-based monolithic column is provided. The method comprises providing a mixture comprising at least one surfactant monomer, at least one crosslinker, at least one initiator, and at least one porogen and polymerizing the mixture to form the surfactant-based monolithic column. The present disclosure also provides a surfactant-based monolithic column, a method for separating molecules, and a process for preparing a surfactant monomer.

Abstract: Glutamic acid derivatives, in particular monatin, may be conveniently prepared by alkylating a 4-protected hydroxyl pyroglutamic acid derivative with an alkylating agent to prepare a 4-protected hydroxyl-4-alkylglutamic acid derivative, followed by the steps of hydrolysis and deprotection. The 4-protected hydroxyl pyroglutamic acid derivative is easy to produce from hydroxyproline. The 4-protected hydroxyl pyroglutamic acid derivative is particularly suitable for use in the efficient manufacture of monatin of high optical purity, since it can be alkylated selectively at the 4-position and stereoselectively and after its alkylation, it can easily be converted to a glutamic acid derivative.

Abstract: This invention provides a method of producing a large amount of an ?-form or ?-form of N-pyranosyl-tryptophan having a specified structure and preparing an antibody therefrom. The method comprises a step of allowing a pyranose compound to react with a 3-pyrazyl-indole compound in the presence of a first base to obtain a 1-pyranosyl-3-pyrazyl-indole compound, and a step of treating the 1-pyranosyl-3-pyrazyl-indole compound with an acid, treating the resultant with a hydrogenation catalyst, and further treating the resultant with a second base to synthesize N-pyranosyl-tryptophan, thereby producing an antibody therefrom.

Abstract: An object of the present invention is to provide novel ribozyme systems capable of catalyzing tRNA acylation using various carboxylic acids as acyl donors and uses thereof. Disclosed is a ribozyme catalyzing tRNA acylation having a structure consisting of the RNA sequence represented by (formula 1): P1-Z1Z2Z3Z4(N1)1(N1)2 . . . (N1)p—P2-(N2)1(N2)2 . . . (N2)qY1Y2Y3(N3)1(N3)2N4GGN wherein (N1)1-(N1)p each independently represent any monoribonucleotide of U, C, A and G; p represents 3 or 4; (N2)1-(N2)q each independently represent any monoribonucleotide of U, C, A and G; q represents 5 or 6; (N3)1-(N3)2 each independently represent any monoribonucleotide of U, C, A and G; N4 represents any monoribonucleotide of U, C, A and G; Z1-Z4 each independently represent C or G; Y1-Y3 each independently represent C or G; N represents a monoribonucleotide complementary to A or G; and P1 and P2 represent a domain consisting of any RNA sequence capable of having a stem-loop structure.

Abstract: Organic compounds having nitrogen atoms protected with t-butoxycarbonyl are effectively deprotected by heating in a fluorinated alcohol solution.

Abstract: Methods and materials for the production of the high intensity sweetener, monatin, in stereoisomerically-pure or stereoisomerically-enriched form are disclosed. For example, methods using stereoisoselective hydrolysis and separation of a monatin-derived lactone ester are disclosed.

Abstract: This invention relates to novel macrocyclic lactams intermediates useful for the preparation of diazonamide analogs. This invention also relates to a novel electrochemical oxidative cyclization for the preparation of such macrocyclic lactams, and their further elucidation to provide diazonamide analogs.

Abstract: The present invention relates to a process for producing efficiently glutamic acid derivatives (including salts thereof) such as monatin by converting a substituted ?-keto acid of formula (1) into a glutamic acid derivative of formula (2) in the presence of an enzyme catalyzing conversion of the same

Abstract: Processes for extracting amino acids from mixtures of amino acids, and compositions and mixtures formed therefrom. Applications include isolating natural L-?-3-indolylalanine (L-?-3) and providing natural or other amino acid mixtures enriched with the extracted L-?-3. The source of amino acids may include a natural source, such as enzymatic or other natural protein hydrolysates containing mixtures of free amino acids. The process includes contacting the mixture of amino acids with a resin or hydrophobic substance that is attractive to aromatic amino acids but not attractive to aliphatic amino acids to separate the aromatic amino acids from the rest of the mixture. This contacting may include agitating the mixture and hydrophobic substance to increase contact therebetween. The L-?-3 may then be separated from the monocylic amino acids by contacting the hydrophobic substance with an acid, and L-?-3 may be removed from the hydrophobic substance by contact with a base.

Abstract: The present invention relates to a method for introducing an amino group into an organic acid or an organic ester by reacting an organic salt or an organic ester and ammonia under high-temperature and high-pressure water conditions, a method for synthesizing an amino acid or an amino ester by the above method, and a method for manufacturing an amino acid compound by synthesizing an amino acid or an amino ester by the above method and separating and refining it with an ion exchange resin.

Abstract: The present invention relates to a method for introducing an amino group into an organic acid by reacting the organic acid and ammonia under high-temperature and high-pressure water conditions, a method for synthesizing an amino acid by reacting an organic acid and ammonia under high-temperature and high-pressure water conditions, and thereby introducing amino group into the organic acid to synthesize an amino acid, and a method for manufacturing an amino acid by reacting an organic acid and ammonia under high-temperature and high-pressure water conditions, thereby introducing an amino group into the organic acid to synthesize an amino acid, and then separating and refining it with an ion exchange resin.

Abstract: Processes for extracting amino acids from mixtures of amino acids, and compositions and mixtures formed therefrom. Applications include isolating natural L-&bgr;-3-indolylalanine (L-&bgr;-3) and providing natural or other amino acid mixtures enriched with the extracted L-&bgr;-3. The source of amino acids may include a natural source, such as enzymatic or other natural protein hydrolysates containing mixtures of free amino acids. The process includes contacting the mixture of amino acids with a resin or hydrophobic substance that is attractive to aromatic amino acids but not attractive to aliphatic amino acids to separate the aromatic amino acids from the rest of the mixture. This contacting may include agitating the mixture and hydrophobic substance to increase contact therebetween. The L-&bgr;-3 may then be separated from the monocylic amino acids by contacting the hydrophobic substance with an acid, and L-&bgr;-3 may be removed from the hydrophobic substance by contact with a base.

Abstract: Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. A method of preparing a 2-alkyl amino acid involves a Michael-type addition of a nucleophile to a dialkyl 2-methylidenylpropan-1,3-dioate and the conversion of a ester moiety into an amino moiety. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, an aryl nitrile or imidate is condensed with cysteine, a 2-alkyl cysteine, or a cysteine ester.

Abstract: Disclosed are a process for preparation of an optically active 7-substituted 3-(2-aminopropyl)indole compound and an intermediate therefor. In the above preparation process, 7-substituted indole is reacted with L- or DL-serine in the presence of a tryptophan-synthesizing enzyme originating in microorganisms to form corresponding 7-substituted L-tryptophan, and it is subjected, if necessary, to reduction, protection, exchange and elimination.

Abstract: The present invention provides a process for efficiently producing an optically active &agr;-amino acid and an optically active &agr;-amino acid amide. After contacting with cells or processed cells thereof having an ability to asymmetrically hydrolyse, a water solvent is substituted with at least one solvent selected from the group consisting of linear, branched, or cyclic alcohol having 3 or more carbon atoms and the optically active &agr;-amino acid is preferentially precipitated from the alcohol solution.

Abstract: The invention provides methods, apparatus, and systems for performing high-throughput preparation and screening of salts and polymorphs of drug candidates. The invention is directed towards enhancing the pre-formulation discovery process used for drug development. In particular, processes that determine suitable salts and processes that discover substantially every polymorph that can form from a particular drug candidate are provided. The processes are performed using several apparatuses that are specifically configured to carry-out various steps in a high-throughput characterization process. One such apparatus is configured for synthesizing a plurality of library members based on, for example, a library model generated by a computer system. Another apparatus may filter the synthesized solution to provide a substantially pure mixture that can be subjected to salt or polymorph testing.

Abstract: The present invention is directed to a method for producing amino acids by reacting halogenated carboxylic acid ester (haloacid esters) with a metal cyanate in the presence of an alcohol and by subsequent acidic saponification of the urethane carbonic acid formed. The method is characterized by the metal cyanate being placed at an elevated temperature in an organic solvent and the other reactants being continuously charged into the mixture over a defined time period.

Abstract: The present invention relates to a process for the catalytic preparation of N-acylglycine derivatives. More particularly, the present invention relates to a process for the catalytic preparation of N-acylglycine derivatives by reacting an aldehyde with a carboxamide and carbon monoxide in the presence of a palladium compound, an ionic halide and an acid as catalyst.

Abstract: Processes for isolating substantially pure natural L-&bgr;-3-indolylalanine (L-&bgr;-3) from a mixture of amino acids, such as a protein hydrolysate. A protein hydrolysate, for example of casein or soy protein, is passed over a polymeric resin attractive to aromatic amino acids but not attractive to aliphatic amino acids. The aromatic amino acids are retained on the resin while the aliphatic amino acids pass over the resin and are collected. The resin is then washed to displace any residual aliphatic acids which may be physically associated with but not bound to the resin. Thereafter, the resin is eluted with a dilute acid to displace L-phenylalanine and L-tyrosine and provide a solution thereof while allowing L-&bgr;-3 to be retained on the resin. The resin is then further eluted with a dilute base to displace L-&bgr;-3 from the resin and provide a solution of L-&bgr;-3. Substantially pure natural L-&bgr;-3 is recoverable from this solution.

Abstract: A 2- or 4-nitrobenzenesulfonamide is allowed to react with an alkali metal alkoxide to remove a nitrobenzenesulfonyl group to thereby obtain an amine corresponding to the amide. Furthermore, a method for producing an amine derivative by allowing the resulting amine without isolation to react with an activated, substituted oxycarbonyl compound or an activated acyl compound is provided. According to this method, a corresponding free amine and its substituted derivative can be produced easily and industrially advantageously from the 2- or 4-nitrobenzenesulfonamide without using a thiol compound.

Abstract: Processes for isolating substantially pure natural L-&bgr;-3-indolylalanine (L-&bgr;-3) from a mixture of amino acids, such as a protein hydrolysate. A protein hydrolysate, for example of casein or soy protein, is passed over a polymeric resin attractive to aromatic amino acids but not attractive to aliphatic amino acids. The aromatic amino acids are retained on the resin while the aliphatic amino acids pass over the resin and are collected. The resin is then washed to displace any residual aliphatic acids which may be physically associated with but not bound to the resin. Thereafter, the resin is eluted with a dilute acid to displace L-phenylalanine and L-tyrosine and provide a solution thereof while allowing L-&bgr;-3 to be retained on the resin. The resin is then further eluted with a dilute base to displace L-&bgr;-3 from the resin and provide a solution of L-&bgr;-3. Substantially pure natural L-&bgr;-3 is recoverable from this solution.

Abstract: A phosgene-free method for preparing a carbamate from a compound containing an amine group involves reacting the compound with an alkylating agent in the presence of carbon dioxide and cesium carbonate. A reaction can take place under standard pressure and temperature conditions and produces carbamates in a high yield with low by-product formation.

Abstract: This invention relates to a method for separating basic amino acids from fermentation broth comprising contacting the broth with strong acid cation exchange resins that have a low degree of cross-linkage and eluting the amino acid. The method described herein results in higher yield and higher purity of lysine, in addition to higher throughput, as compared to conventional processes of purification of lysine from fermentation broth.

Abstract: Amide compounds of formula (I), combinatorial libraries of amide compounds and methods of preparing the same are provided. Libraries of the invention are useful for screening in biological assays in order to identify pharmaceutically useful compounds.

Abstract: A method for recovering amino acids, which comprises supplying a mixed solution containing inorganic acid salts, amino acids and non-electrolytes such as saccharides to a first-step resin layer comprising an Na type or K type strongly acidic ion exchange resin; separating an effluent into at least a first fraction containing coloring matters, acidic amino acids and ashes, a second fraction containing neutral amino acids and saccharides, and a third fraction containing betaines; supplying the second fraction to a second-step resin layer comprising at least one resin selected from the group consisting of NH4 type, Ca type and Mg type strongly acidic ion exchange resins, and optionally further supplying it to a third-step resin layer comprising an Mg type or Ca type strongly acidic ion exchange resin different from the resin of the second-step resin layer, thereby recovering various kinds of amino acids contained in an effluent.

Abstract: The invention provides a novel amino acid, neo-tryptophan, as well as polypeptides containing this novel amino acid such as neurotensin analogs. In addition, the invention provides neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and polypeptides containing such derivatives. The invention also provides methods for making neo-tryptophan, neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and compositions containing these compounds. Further, the invention provides methods for inducing a neurotensin response in a mammal as well as methods for treating a mammal having a serotonin recognition molecule.

Abstract: A method for the crystallization of tryptophan, comprising storing a tryptophan solution at a pH of 8 to 13 and at a temperature of room temperature to 100° C. for 0.5 hour to 1 week and then, followed by crystallization.

Abstract: A method for the crystallization of tryptophan, comprising storing a tryptophan solution at a pH of 8 to 13 and at a temperature of room temperature to 100° C. for 0.5 hour to 1 week and then, followed by crystallization.

Abstract: A compound of formula (I), in which: R1 is lower alkyl, cyclo(lower)alkyl, optionally substituted aryl, optionally substituted heterocyclic group, cyclo(lower)alkyl(lower)alkyl, or ar(lower)alkyl; R2 is hydrogen, hydroxy or protected hydroxy; R3 is lower alkyl, aryl, ar(lower)alkyl or optionally substituted heterocyclic(lower)alkyl; R4 is carboxy, protected carboxy or lower alkylsufonylcarbamoyl; R5 is hydrogen or lower alkyl; R6 is hydrogen or heterocyclic group; A is a single bond or lower alkylene, and Ar is optionally substituted aryl, or pharmaceutically acceptable salts thereof, having endothelin antagonistic activity.

Abstract: A process for isolating substantially pure natural L-.beta.-3-indolylalanine (L-.beta.-3) from a mixture of amino acids, such as a protein hydrolysate, is described. A protein hydrolysate, for example of casein or soy protein, is passed over a polymeric resin attractive to aromatic amino acids but not attractive to aliphatic amino acids. The aromatic amino acids are retained on the resin while the aliphatic amino acids pass over the resin and are collected. The resin is then washed with water to displace any residual aliphatic acids which may be physically associated with but not bound to the resin. Thereafter, the resin is eluted with a dilute acid to displace L-phenylalanine and L-tyrosine and provide a solution thereof while allowing L-.beta.-3 to be retained on the resin. The resin is then further eluted with a dilute base to displace L-.beta.-3 from the resin and provide a solution of L-.beta.-3. Substantially pure natural L-.beta.-3 is recoverable from this solution.

Abstract: Synthetic mammalian matrix metalloprotease inhibitors are disclosed that are useful for treating or preventing diseases wherein said diseases are caused by unwanted mammalian matrix metalloprotease activity and include skin disorders, keratoconus, restenosis, rheumatoid arthritis, wounds, cancer, angiogenesis and shock.

Abstract: The present application describes amidinoindoles, amidinoazoles, and analogs thereof of formula I: ##STR1## wherein W, W.sup.1, W.sup.2, and W.sup.3 are selected from CH and N, provided that one of W.sup.1 and W.sup.2 is C(C(.dbd.NH)NH.sub.2) and at most two of W, W.sup.1, W.sup.2, and W.sup.3 are N and one of J.sup.a and J.sup.b is substituted by --(CH.sub.2).sub.n --Z--A--B, which are useful as inhibitors of factor Xa or thrombin.

Abstract: A process for improving the solubility of hydrophobic amino acids in which hot saturated aqueous solutions of at least two different amino acids are first combined. A first step includes making a hot saturated aqueous solution of a first and hydrophobic amino acid having a low solubility in water. A second step includes making a hot saturated aqueous solution of a second and hydrophilic amino acid having a high solubility in water. Then the two hot saturated aqueous solutions are mixed to prepare a combined hot solution mixture, and dried. The resulting product is an amino acid food supplement which is blended into animal feed. The preferred amino acids are tryptophan and lysine, when the animal is a domestic farm animal. A preferred ratio is where the concentration of tryptophan is greater than 50 grams per liter and the concentration of lysine is greater than 300 grams per liter.

Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.

Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.