Abstract: The present invention provides a method to label phospholipids in vivo based on the metabolic incorporation of an alkynyl- or azido-labeled metabolic precursor into phospholipids. The resulting phospholipids have alkynyl or azido moieties, which, upon reaction with a labeled azide or alkyne, respectively, form labeled compounds that can be visualized using optical or electron microscopy with high sensitivity and spatial resolution in cells or tissue. The present method provides a valuable tool for imaging phospholipid synthesis, turnover and subcellular localization in cultured cells as well as in animals.

Abstract: The present invention discloses novel process for the preparation of (2R)-2-acetamido-N- benzyl-3-methoxypropanamide of Formula I involving novel intermediates of Formula-XIX and Formula-XX.

Abstract: This invention pertains to methods for producing homogeneous recombinant proteins that contain polymer initiators at defined sites. The unnatural amino acid, 4-(2?-bromoisobutyramido)phenylalanine of formula 1, was designed and synthesized as a molecule comprising a functional group further comprising an initiator for an atom-transfer radical polymerization (‘ATRP”) that additionally would provide a stable linkage between the protein and growing polymer. We evolved a Methanococcus jannaschii (Mj) tyrosyl-tRNA synthetase/tRNACUA pair to genetically encode this unnatural amino acid in response to an amber codon. To demonstrate the utility of this functional amino acid, we produced Green Fluorescent Protein with the unnatural amino acid initiator of formula 1 site-specifically incorporated on its surface (GFP-1).

Abstract: Described herein is a composition comprising at least one of: X—R—(Z)n wherein X is selected from: an aziridine amide, an aziridine urea, an isocyanate, an alcohol, an amine, an epoxy, or a sulfhydryl, R is a multifunctional organic group, and Z is selected from —N3 or —C?C—R?, wherein R? is a hydrogen or a monofunctional organic group and n is from one to about 10. Also, described are mixtures, curable polymeric compositions, and methods of making cured polymeric compositions.

Abstract: The invention relates to conjugates of macromolecular carriers and drugs comprising linkers that release the drug or a prodrug through rate-controlled beta-elimination, and methods of making and using the conjugates.

Abstract: Polymers having orthogonal reactive groups and solid supports comprising polymers immobilized thereto are provided. The polymers find utility in any number of applications including immobilizing analyte molecules to solid supports for high throughput assays.

Abstract: Provided herein are novel alkynyl and azide containing amino acids; kits containing these amino acids; peptides containing these amino acids; peptide macrocycles whose secondary structures are stabilized with linkers containing triazoles synthesized by reacting the side chains of the alkynyl and azide containing amino acids; and methods of making and using the alkynyl and azide containing amino acids, kits, peptides, triazole containing linkers, and peptide macrocycles.

Abstract: There is provided a process for the preparation of Lacosamide (which is a useful medicament) of formula I, which comprises an enantioselective enzymatic acylation.

Abstract: The present invention provides novel process for the preparation of renin inhibitor Aliskiren or its derivatives, and its pharmaceutically acceptable salts. The present invention also provides novel intermediates used in the preparation of Aliskiren.

Abstract: This invention pertains to methods for producing homogeneous recombinant proteins that contain polymer initiators at defined sites. The unnatural amino acid, 4-(2?-bromoisobutyramido)phenylalanine of formula 1, was designed and synthesized as a molecule comprising a functional group further comprising an initiator for an atom-transfer radical polymerization (‘ATRP”) that additionally would provide a stable linkage between the protein and growing polymer. We evolved a Methanococcus jannaschii (Mj) tyrosyl-tRNA synthetase/tRNACUA pair to genetically encode this unnatural amino acid in response to an amber codon. To demonstrate the utility of this functional amino acid, we produced Green Fluorescent Protein with the unnatural amino acid initiator of formula 1 site-specifically incorporated on its surface (GFP-1).

Abstract: The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs.

Abstract: This invention relates to processes and intermediates for the preparation of an alpha-amino beta-hydroxy acid of Formula 1 wherein the variables R1, R?1 and R2 are defined herein and the compound of Formula 1 has an enantiomeric excess (ee) of 55% or greater.

Abstract: The present invention discloses novel process for the preparation of (2R)-2-acetamido-N-benzyl-3-methoxypropanamide of Formula I involving novel intermediates of Formula-XIX and Formula-XX.

Abstract: The invention relates to conjugates of macromolecular carriers and drugs comprising linkers that release the drug or a prodrug through rate-controlled beta-elimination, and methods of making and using the conjugates.

Abstract: Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein.

Abstract: Clickable polyunsaturated fatty acid analogs, methods of using these analogs and kits comprising these analogs.

Abstract: The present invention is to provide manufacturing intermediates which can be led to useful ?-ketoamide compounds having protease-inhibiting activity extremely economically and stereoselectively, and to provide epoxycarboxamide compounds, azide compounds and amino alcohol compounds represented by the following formulae: wherein R1 and R2 each represents alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group; R3 represents alkyl group, alkenyl group, aromatic hydrocarbon group, heterocyclic group, R6—O— or R7—N(R8)—; where R6 represents alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group; R7 and R8 each represents hydrogen atom, alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group, and, R4 and R5 represent the same groups as R7 and R8, respectively, and R4 and R5 optionally form a ring together; and X represents —O— or —N(R9)—, where R9 represents hydrogen atom or alkyl group, and X optionally forms a ring together with R4 or R5, and

Abstract: The invention relates to a method of making a polypeptide comprising an orthogonal functional group, said orthogonal functional group being comprised by an aliphatic amino acid or amino acid derivative, said method comprising providing a host cell; providing a nucleic acid encoding the polypeptide of interest; providing a tRNA-tRNA synthetase pair orthogonal to said host cell; adding an amino acid or amino acid derivative comprising the orthogonal functional group of interest, wherein said amino acid or amino acid derivative is a substrate for said orthogonal tRNA synthetase, wherein said amino acid or amino acid derivative has an aliphatic carbon backbone; and incubating to allow incorporation of said amino acid or amino acid derivative into the polypeptide of interest via the orthogonal tRNA-tRNA synthetase pair. The invention also relates to certain amino acids, and to polypeptides comprising same.

Abstract: The present invention provides a method to label phospholipids in vivo based on the metabolic incorporation of an alkynyl- or azido-labeled metabolic precursor into phospholipids. The resulting phospholipids have alkynyl or azido moieties, which, upon reaction with a labeled azide or alkyne, respectively, form labeled compounds that can be visualized using optical or electron microscopy with high sensitivity and spatial resolution in cells or tissue. The present method provides a valuable tool for imaging phospholipid synthesis, turnover and subcellular localization in cultured cells as well as in animals.

Abstract: The present invention features a chemoselective ligation reaction that can be carried out under physiological conditions. In general, the invention involves condensation of a specifically engineered phosphine, which can provide for formation of an amide bond between the two reactive partners resulting in a final product comprising a phosphine moiety, or which can be engineered to comprise a cleavable linker so that a substituent of the phosphine is transferred to the azide, releasing an oxidized phosphine byproduct and producing a native amide bond in the final product. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo (e.g., on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).

Abstract: The present invention provides a nanocarrier having an interior and an exterior, the nanocarrier comprising at least one conjugate, wherein each conjugate includes a polyethylene glycol (PEG) polymer. Each conjugate also includes at least two amphiphilic compounds having both a hydrophilic face and a hydrophobic face. In addition, each conjugate includes an oligomer, wherein at least 2 of the amphiphilic compounds are covalently attached to the oligomer which is covalently attached to the PEG. The nanocarrier is such that each conjugate self-assembles in an aqueous solvent to form the nanocarrier such that a hydrophobic pocket is formed in the interior of the nanocarrier by the orientation of the hydrophobic face of each amphiphilic compound towards each other, and wherein the PEG of each conjugate self-assembles on the exterior of the nanocarrier.

Abstract: The invention provides water-soluble compounds that include a polymer and at least one terminal azide or acetylene moiety. Also provided are highly efficient methods for the selective modification of proteins with PEG derivatives, which involves the selective incorporation of non-genetically encoded amino acids, e.g., those amino acids containing an azide or acetylene moiety, into proteins in response to a selector codon and the subsequent modification of those amino acids with a suitably reactive PEG derivative.

Abstract: The invention relates to the compounds suitable for radiolabeling with a chelator free radioisotope and radiolabeled compounds of the general Formula I. Said compounds are ornithine or lysine derivatives.

Abstract: Azide compositions selected from i) UOCR2CR2N3 wherein U is D, or a urethane (—CO—NR2) and R is independently H, D, or an organic group; ii) R?2NCR2CR2N3 or A-R?3NCR2CR2N3 wherein R? is an organic group and A is an anion; or iii) G(N3)m wherein m is an integer from 2 to about 10 and G is a m-valent organic group wherein at least two of the azido groups are connected via aliphatic carbon atoms wherein G may contain organic groups, and uses thereof are described. Specifically, the azide compositions selected from the group consisting of: N3CH2CH2OCH2CHOHCH2N3, CH3OCH2CHOHCH2N3, CH3OCH2CH(OCONHC4H9)CH2N3, N3CH2CH2O[CH2CH(CH2N3)O]6H, CH3CH2C[CH2(OCH2CH(CH2N3))2OCOCH3]3N3CH2CH2OCONH(CH2)6NHCOOCH2CH2N3, (CH3)3CNHCOOCH2CH2N3, n-C4H9NDCOOCH2CH2N3, C6H5N—HCOOCH2CH2N3, C4F9OCFCF3NDCOOCH2CH2N3, DOCH2CH2N3, and [(CH3)3NCH2CH2N3]+I are described.

Abstract: Aspects of the present invention are directed to novel methods for making discrete polyethylene compounds selectively and specifically to a predetermined number of ethylene oxide units. Methods which can be used to build up larger dPEG compounds (a) containing a wider range of utility to make useful homo- and heterofunctional and branched species, and (b) under reaction configurations and conditions that are milder, more efficient, more diverse in terms of incorporating useful functionality, more controllable, and more versatile then any conventional method reported in the art to date. In addition, the embodiments of the invention allow for processes that allow for significantly improving the ability to purify the intermediates or final product mixtures, making these methods useful for commerial manufacturing dPEGs. Protecting groups and functional groups can be designed to make purification at large scale a practical reality.

Abstract: Described herein is a mixture comprising: a non-self-crosslinking polymer; and a modifying compound comprising at least two different functional groups. The first functional group of the modifying compound is capable of reacting with the non-self-crosslinking polymer and the second functional group is capable of crosslinking with a curing agent. Also, described are compositions, curable polymeric compositions, articles using such curable polymeric compositions, and methods of making cured polymeric compositions.

Abstract: The present invention provides novel and advantageous processes for preparing and purifying chemical compounds such as pharmaceuticals. The processes comprise a nucleophilic substitution reaction with a moiety X wherein the leaving group L of a substrate S in the reaction is covalently attached to a purification moiety M. This concept offers a convenient and lime-saving way to purity the desired product S-X from non-reacted precursors S-L-M and by-products L-M.

Abstract: The present invention describes the modification of polypeptides, more particularly channel proteins with a thiol reactive agent so as to introduce an azide group. The present invention further describes vesicles comprising channel proteins modified according to the invention, which upon reaction with a phosphine open up thereby releasing the content of the vesicles. The reagents, polypeptides and vesicles described in the present invention have in vivo and in vitro applications in both drug delivery and imaging.

Abstract: The present invention provides bifunctional polymers, methods of preparing the same, and intermediates thereto. These compounds are useful in a variety of applications including the PEGylation of biologically active molecules. The invention also provides methods of using said compounds and compositions thereof.

Abstract: Methods and protected amino acids useful as building blocks (protected monomers) for the synthesis of peptides and proteins that are selectively modified at one or more side-chain hydroxyl groups. Azide-bearing protecting groups allow the selective deprotection of side-chain hydroxyl groups of amino acids after synthesis of a peptide. Reaction conditions for removal of the azide-bearing protecting group can be selected which are substantially orthogonal to those that will remove ?-amino protecting groups typically employed in peptide synthesis, such that hydroxyl groups protected with the azide-bearing protecting group remain protected during synthesis of the peptide chain. Various protecting groups which are readily available can be used for protecting potentially reactive side chain groups of amino acids in the peptide or protein to be modified.

Abstract: A process for enantioselectively preparing 3-azidocarboxylic acid derivatives comprises reacting 3-sulfonatocarboxylic acid derivatives with an alkali metal azide in a solvent selected from the group comprising certain carboxamides; a solvent mixture which comprises such carboxamides; a solvent mixture of water and a solvent miscible homogeneously with water; water with the proviso that the addition of a phase transfer catalyst is not used in the reaction in water; and DMSO. The resulting products are optionally reduced to 3-aminocarboxylic acid derivatives.

Abstract: The invention provides methods and compositions for azide tagging of biomolecules. In one embodiment of the invention, proteins are tagged by metabolic incorporation of prenylated azido-analog substrates. Examples of such analogs are azido farnesyl diphosphate and azido farnesyl alcohol. The azido moiety in the resulting modified proteins provides an affinity tag, which can be chemoselectively captured by an azide-specific conjugation reaction, such as the Staudinger reaction, using a phosphine capture reagent. When the capture agent is biotinylated, the resulting conjugates can be detected and affinity-purified by streptavidin-linked- HRP and streptavidin-conjugated agarose beads, respectively. The invention allows detection and isolation of proteins with high yield, high specificity, and low contamination without harsh treatment of proteins.

Abstract: A process for producing an optically active 3-azide-carboxylic acid ester by reacting an optically active 3-hydroxycarboxylic acid ester and a thionyl halide in the presence of a basic substance in an organic solvent to produce an optically active 3-halogenocarboxylic acid ester which is then reacted with an azide salt represented by the formula: MN3 (wherein M is an alkaline metal) in water or a mixture of water and a water soluble organic solvent.

Abstract: A process for producing an optically active 3-azide-carboxylic acid ester by reacting an optically active 3-hydroxycarboxylic acid ester and a thionyl halide in the presence of a basic substance in an organic solvent to produce an optically active 3-halogenocarboxylic acid ester which is then reacted with an azide salt represented by the formula: MN3 (wherein M is an alkaline metal) in water or a mixture of water and a water soluble organic solvent.

Abstract: The present invention is to provide manufacturing intermediates which can be led to useful &agr;-ketoamide compounds having protease-inhibiting activity extremely economically and stereoselectively, and to provide epoxycarboxamide compounds, azide compounds and amino alcohol compounds represented by the following formulae: 1

Abstract: This invention relates to positively charged non-natural amino acids, methods of making thereof, and utilization thereof in peptides.

Abstract: A subject-matter of the present invention is novel polyglycidyl azides of general formula (I): in which: R1 represents an alkylene chain comprising 2 to 4 carbon atoms, R2 represents an alkyl chain comprising 1 to 4 carbon atoms, x represents an integer such that 4≦x≦10. These compounds are not detonatable and are of use in particular as energetic plasticizers in solid pyrotechnic compositions. They can be obtained according to a 3-stage process starting from epichlorohydrin by preliminary synthesis of polyepichlorohydrin with a hydroxyl terminal group of formula (II): then acylation of this compound in order to obtain a polyepichlorohydrin with an acyloxy terminal group of formula (IV): and then azidation of this compound.

Abstract: The present invention relates to the compound of formulae ##STR1## and to a process for the manufacture of compounds of the general formula ##STR2## which are ligands for the metabotropic glutamate receptors of group II, whereinT is tritium;R.sup.1 is hydroxy, lower alkoxy, lower alkenyloxy, benzyloxy, hydrogen, deuterium or tritium;R.sup.11 is hydrogen, deuterium or tritium, hydroxy or amino, andR.sup.2 is hydrogen or tritium, orR.sup.1 and R.sup.2 form a bond.

Abstract: Synthesis of a vinyl terminated polymer by reacting a cationically polymeable monomer in the form of a cyclic ether with an acid chloride in a suitable solvent and in the presence of a Lewis acid. The vinyl-terminated polymers can be polymerized with other appropriate monomers resulting in thermoplastic elastomers having suitable properties for use as binders for explosives and propellants.

Abstract: The present invention provides a purified retinoid compound characterized by a molecular mass of about 320 daltons and an atomic composition of C.sub.20 H.sub.32 O.sub.3. The present invention also provides a purified retinoid compound having the structure: ##STR1## wherein the configuration of the C7, C9, and C11 double bond independently is Z or E and the absolute configuration at C13 and C14 is independently R or S; wherein R1 is alkyl, alkyl halide, alcohol, ester, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, acyl halide, amide, nitrile, or amine; R2 and R3 are independently hydroxyl, halide, alkoxy, ester, alkyl, alcohol, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, nitrile, amine, azide, alkyl halide, acid halide, acid azide, or amide; or wherein R2 and R3, or R1 and R2 are replaced by a 13,14-oxirane or a 14,15-oxirane group, respectively.

Abstract: Difunctional, hydroxyl-terminated polymers in which the terminal hydroxyl group is non-primary or hindered are end-capped to provide unhindered, primary, terminal hydroxyl groups which promote an improved cure and improved mechanical properties of the cured elastomer. End-capping chemicals have an hydroxyl-reactive group at one end and a group at the other end which is removable to provide a primary, unhindered hydroxyl group. Short-chain, hydroxyl-terminated polymers are chain-extended with a diisocyanate.

Abstract: Certain N-acetonylbenzamides exhibit low toxicity to plants are particularly useful for control of fungi, especially Phycomycetes.

Abstract: A process and intermediates for the enantioselective synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid are disclosed.

Abstract: The present invention provides novel 2-aliphatic or arylaliphatic cyclopentane heptanoic and heptenoic acid derivatives including at least one azido substituent. In particular 2-aliphatic or arylaliphatic cyclopentane heptenyloic and cyclopentane heptanoic acids and esters thereof, substituted at the 3 and/or 5 position of the cyclopentane ring with radicals selected from the group consisting of hydroxy, azido and mixtures thereof, are disclosed. These azido compounds are useful as ocular hypotensives and are intermediates for the preparation of other compounds useful as ocular hypotensives.

Abstract: A process and intermediates for the enantioselective synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid are disclosed.

Abstract: A process and intermediates for the enantioselective synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid are disclosed.

Abstract: Glycidyl azide polymer esters for use in insensitive gun and rocket propellants having pendant terminated azide ester groups and a method for producing same.

Abstract: Energetic azido curing agents are provided for curing hydroxy-terminated aliphatic polymers having pendant alkyl azide groups.

Abstract: Glycidyl azide polymer esters for use in insensitive gun and rocket propellants having pendant terminated azide ester groups and a method for producing same.

Abstract: Provided herein are the compounds 4,4-dinitro-1-butanol, 4-azido-4,4-dinitro-1-butyl acetate and methods for preparing each compound.4,4-dinitro-1-butanol is prepared by reacting trinitromethane with acrolein, reducing the resulting trinitroaldehyde to provide the corresponding alcohol and reducing the alcohol.4-azido-4,4-dinitro-1-butyl acetate is prepared by reacting 4,4-dinitro-1-butanol with acetyl chloride to yield the corresponding acetate and reacting the acetate with an alkali metal azide in an electrolysis cell.