Abstract: Lipid conjugates of a poly-(amino acid), a poly-(amino acid derivative) or a poly-(amino acid analogue), such as poly-[N-(2-hydroxyethyl)-glutamine](PHEG), are provided.

Abstract: Mixtures of conjugates in which each conjugate in the mixture comprises a growth hormone drug coupled to an oligomer that includes a polyalkylene glycol moiety wherein the mixtures have a molecular weight distribution with a standard deviation of less than about 22 Daltons are disclosed. Methods of treating growth hormone deficiency in a subject in need of such treatment and methods of accelerating the growth rate of an animal arc also disclosed. Processes for synthesizing substantially monodispersed mixtures of conjugates wherein each conjugate comprises a growth hormone drug coupled to an oligomer that comprises a polyethylene glycol moiety are further provided.

Abstract: The invention relates to novel amphiphilic complexes, a method for their preparation, and the compositions containing them. Said amphiphilic complexes result from the reaction, at a temperature between ambient temperature and 80° C., between a protein or polypeptide whose average molecular mass is greater than or equal to 5,000 Daltons and a fatty chain whose carbon atom number is between 4 and 30 selected from fatty acid, fatty alcohol, fatty amine, with the exclusion of undecylenic acid ; the protein or polypeptide/fatty chain weight ratio ranging from 1000/1 to 1/10.

Abstract: A molecular conjugate is provided having the formula: wherein n is the conjugation number, P is a moiety of a carrier molecule such as a protein, R1 is a moiety of a biologically active molecule or its analogs, derivatives, salts or secondary amines, Z is —O— or —NH—, and Y is a straight or branched alkyl having 1 to 20 carbons optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl, electron-withdrawing or electron-donating groups. Compounds and methods useful in producing such molecular conjugates are also provided, as well as methods of concentrating biologically active molecules in selected target cells of a patient that comprise administering to the patient a selected dose of such molecular conjugates.

Abstract: The present invention relates to conjugates for mediating a cell-specific, compartment-specific or membrane-specific to methods of active substances. The invention also relates to methods of preparing these conjugates as well as their use. The conjugates comprise: a transport mediator for the cell membrane, a cell-specific, compartment-specific or membrane-specific address protein or peptide, and an active substance to be transported.

Abstract: The invention provides reagents and methods for characterizing (i.e., identification and/or quantitation) the phosphorylation states of proteins. Proteins may be post-transcriptionally modified such that they contain phosphate groups at either some or all of their serine, threonine, tyrosine, histidine, and/or lysine amino acid residues. In many cases the extent to which a protein is phosphorylated determines it bioactivity, i.e., its ability to effect cell functions such as differentiation, division, and metabolism. Hence, a powerful tool for diagnosing various diseases and for furthering the understanding of protein—protein interactions is provided.

Abstract: A hedgehog conjugate which is characterized in that it contains: a) a polypeptide composed of 10 to 30 hydrophobic amino acids and/or amino acids which form transmembrane helices and are positively charged, b) 1 to 4 aliphatic, saturated or unsaturated hydrocarbon residues with a chain length of 10 to 24 C atoms and with a hydrophobic action or c) a hydrophobic thio compound covalently bound to a hedgehog protein and which has a several-fold increased activity and is suitable as a pharmaceutical agent.

Abstract: A method is disclosed for stabilizing porous silicon. A porous silicon structure having a surface terminated with hydrogen atoms is subjected to organic thermal processing to substitute the hydrogen atoms with a protective organic layer. The resulting structure are found to have unprecedented stability.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: Hollow particles for use in various types of assay devices are provided. Due to their hollow or voided structure, the particles may exhibit a variety of beneficial properties. For instance, hollow particles are generally lightweight, and thus, relatively inexpensive in comparison to other types of particles. Hollow particles may also form a stable system without requiring refrigeration or rotation. In addition, hollow particles may possess enhanced light diffraction capabilities, which may be particularly beneficial in certain types of assay devices, e.g., diffraction-based assay devices.

Abstract: The present invention provides a hapten-carrier conjugate as antigen having haptenic mannitol epitopes, the invention also provides a method of preparing hapten-carrier conjugate as immunogen possessing mannitol groups or epitopes to raise antibodies specific to D-mannitol and the present invention further provides a use of hapten-carrier conjugate as an antigen to detect D-Mannitol specific human IgE.

Abstract: A method of bonding a substance to be incorporated into a free terminal of a water-soluble polymer compound chain, characterized by reacting a reactive functional group present at the free terminal of the water-soluble polymer compound chain which is bonded at a binding terminal thereof in the manner of bristles of a brush onto a surface of a base material; with the substance to be incorporated capable of reacting with the reactive functional group; in the presence of a water-soluble polymer compound which promotes the bonding, is disclosed.

Abstract: The present invention relates to a method of identifying a polypeptide, which method comprises the steps of (a) derivatization of the N-terminus of the polypeptide, or the N-termini of one or more peptides of the polypeptide, with at least one acidic reagent which comprises a sulfonyl moiety coupled to an activated acid moiety to provide one or more peptide derivatives; analyzing at least one such derivative using a mass spectrometric technique to provide a fragmentation pattern, and (c) interpreting the fragmentation pattern obtained, wherein the peptide or polypeptide is immobilized to a solid support at least during step(a). Furthermore, the present invention also relates to a kit for identifying a polypeptide by a mass spectrometric technique.

Abstract: The present invention relates to stilbene and quinone compounds related to combretastatin A-4 and their use as anticancer compounds and prodrugs. The compounds include those with an alkyl group on the double bond of cis or trans-stilbenes, compounds with one or more (and preferably 2 or 3) alkyl group substituents on the stilbene A ring, compounds with an alkoxy group other than methoxy at position 3, 4, and/or 5 of the stilbene A ring, compounds (or prodrugs) in which BOC amino acid esters are formed with the phenolic hydroxyl at the 3-position of the B ring and compounds (or prodrugs) based on a benzoquinone B ring. The present invention further relates to the photochemical reactions of stilbene compounds, either the above compounds disclosed for the first time herein or compounds based on prior art stilbenes.

Abstract: Substrates (e.g., polymer), and/or solid supports (e.g., glass) having one or more biomolecule-binding compounds covalently bound to the surface of the substrate or solid support reversible covalent attachment of biomolecules thereto.

Abstract: A process for preparing a protein-polysaccharide conjugate includes reacting a protein with a polysaccharide to produce a mixture including a protein-polysaccharide conjugate and free protein. At least one unreacted reagent or low molecular weight component is removed from this mixture, without removing all of the free protein, to provide a purified mixture that contains the protein-polysaccharide conjugate and free protein. This purified mixture can be used as a conjugate vaccine, immunogen, or immunological reagent. Keeping the free protein in the purified mixture with the conjugate saves time and money in the conjugate production process. In another aspect of the invention, the purified mixture of the protein-polysaccharide conjugate and free protein is reacted with a hapten to produce a conjugate mixture including a hapten-protein conjugate and a hapten-protein-polysaccharide conjugate.

Abstract: Disclosed are methods of conjugating biologically active substances, particularly, alpha-interferon, with a hyaluronan or a mixture of a hyaluronan with at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone. Also disclosed are stable intermediates formed by partially reacting a hyaluronan with divinyl sulfone and stopping the reaction before completion to leave free, or reactive vinyl groups on the hyaluronan molecule available for conjugation with the biologically active substance.

Abstract: Polycation bioconjugates and a method for producing them. The polycations are capable of transporting active substances of different types. The polycations function as carrier molecules that transport enhancer molecules, thereby enhancing the biological effectiveness of the transported molecules. The polycation bioconjugates of the present invention may inhibit malignant cell proliferation, possess antimicrobial effect, or be configured for gene transport.

Abstract: A modifier characterized by containing as the active ingredient a compound represented by the formula (I) (wherein X is OH, OSO3H, or OCH3 and R is a substituent excluding OH). The modifier is applied to a substance having reactivity with the compound.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin.

Abstract: Provided is a method for modifying silicon with an organic molecule, under mild conditions. If the attached molecule is bi-functional, it may be subsequently reacted with a bio-molecule, to form a covalently attached layer of bio-molecule on the silicon surface.

Abstract: Protein and polypeptide derivatives and their salts are claimed characterized in that a protein or polypeptide is conjugated via an intermediate grouping containing at least one radical of the formula —C(R)═N— (or —N═C(R)—) or —CH(R)—NH— (or —NH—CH(R)—), wherein R is hydrogen or a hydrocarbon residue which may be substituted, with the same or a different protein or polypeptide, with a reporter group or a cytotoxic agent as well as a process for their preparation and the novel intermediates therefor.

Abstract: A homogeneous polyoxime composition is provided, in which the polyoxime molecules present comprise a first organic baseplate molecule, which is a polypeptide, wherein the baseplate molecule is linked to at least two second organic molecules, which may be the same or different from one another. In the compositions, the linkages between the baseplate and said organic molecules are oxime linkages formed by reaction of an orthogonal reactive group on each the organic molecules with a complementary orthogonal reactive group on the baseplate.

Abstract: The present invention provides for novel reagents whose fluorescence changes upon cleavage or a change in conformation of a backbone. The reagents comprise a backbone (e.g. nucleic acid, polypeptide, etc.) joining two fluorophores of the same species whereby the fluorophores form an H-dimer resulting in quenching of the fluorescence of the fluorophores. When the backbone is cleaved or changes conformation, the fluorophores are separated, no longer forming an H-type dimer, and are de-quenched thereby providing a detectable signal. The use of a single fluorophore rather than an “acceptor-donor” fluoresecence resonance energy transfer system offers synthesis and performance advantages.

Abstract: The invention is directed primarily to compounds of Formula I: wherein: R1 is a polymeric residue; L1 is a bifunctional linking group; Y1 and Y2 are independently O, S or NR7; R2-7 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy and C1-6 heteroalkoxy; D is a moiety that is a leaving group or a residue of a compound to be delivered into a cell; Z is selected from the group consisting of: a moiety that is actively transported into a target cell, a hydrophobic moiety, and combinations thereof; Ar is a moiety which when included in Formula (I) forms a multi-substituted aromatic hydrocarbon or a multi-substituted heterocyclic group; and (y) is a positive integer greater than or equal to 1. Methods of making and using the same are also disclosed.

Abstract: The present invention includes purified and isolated quassinoids and synthetically derived quassinoid analogs based on a picrasane carbon skeleton. Novel sidechains at C-15 incorporating water solubilizing agents such as glycine are discussed. Therapeutic methods taking advantage of anticancer, antiviral, and herbistatic properties of these quassinoids are disclosed, including use against solid tumors and human immunodeficiency virus infected cells.

Abstract: Compounds of the formulas

Abstract: A method for producing a derivatized aldehydic support matrix material includes activating surface hydroxyl groups on the support matrix material and reacting the activated hydroxyl groups with an aldehydic alkoxy silane. The derivatized aldehydic support matrix material produced is useful for immobilizing bio-molecules in biological applications.

Abstract: An improved process is described for preparing Schiff base condensation adduct final products whose components comprise a protein having beneficial activity in animals, and an aromatic o-hydroxy aldehyde, which comprises bringing together the above-mentioned components in an aqueous environment at a pH of 7.0 or higher to form a reaction mixture, under conditions effective to drive said condensation reaction substantially to completion by removing from about 97.0% to about 99.9% by weight, preferably from about 98.0% to about 99.0% by weight of the water already present or produced during said condensation reaction, consistent with maintaining the integrity of the condensation reactants and adduct final product, and to assure a rate of conversion to said condensation adduct final product, i.e., with resulting yield of said condensation adduct final product of equal to or greater than about 98.5% by weight, preferably equal to or greater than about 99.5% by weight based on the weight of the reactants.

Abstract: Novel drug complexes comprising a polypeptide carrier moiety comprising glutamic acid and at least one of the group consisting of aspartic acid, alanine, asparagine, glutamine, glycine, and any combinations thereof, are disclosed. The drug moiety is a therapeutic metal selected from the group consisting of platinum, iron, gadolinium, rhenium, manganese, cobalt, indium, gallium or rhodium. Methods for making said complexes, compositions comprising said complexes, methods for making saiduch compositions, and methods for treating a patient comprising use of said complexes and/or compositions are further disclosed.

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: In accordance with the present invention, there are provided rapidly crosslinkable polypeptides which are obtained upon introduction of unsaturated group(s) into the polypeptide via linkage to amino acid residues on the polypeptide directly through one of three types of linkages, namely, an amide linkage, an ester linkage, or a thioester linkage. Each of these linkages are obtainable in a single step by use of a single derivatizing agent, acrylic anhydride. Also provided are methods for preparing such modified polypeptides and various uses therefor. It has unexpectedly been found that proteins with the above-described chemical modifications have the ability to rapidly crosslink to themselves under suitable conditions. This crosslinking occurs in the absence of any external crosslinking agents (indeed, in the absence of any extraneous agents), resulting in the formation of a solid gel material. Solid crosslinked gels are formed in seconds, starting from a freely flowing solution of polypeptide.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of protecting one or more sites on the protein, contacting the protected protein with polyethylene glycol under conditions suitable for conjugating the polyethylene glycol to the protein, and deprotecting the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains sterically free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Molded articles formed of polystyrene or other polymers containing an aromatic moiety can be derivatized on the surface of the article by subjecting the molded article to a chemical reaction wherein the reaction media utilizes tetramethylsulfone as the reactant solvent and a suitable substituent group which is substituted on to the aromatic moiety of the polystyrene or other polymer by electrophilic substitution. By choosing the substituent group to further include a leaving group, further substitution of the primary substituent can be effected normally by nucleophilic substitution reaction. In this way, biologically important molecules can be attached to a polystyrene or other aromatic containing polymer without effecting certain properties of the molded article such as its optical or spectroscopic clarity.

Abstract: A method of dewatering fine particulate materials is disclosed. In this method, an aqueous slurry of fine particles is treated with appropriate hydrophobizing reagents so that the particulate material becomes moderately hydrophobic. A lipid of vegetable or animal origin is then added to the slurry in solutions of light hydrocarbon oils and short-chain alcohols, so that the hydrophobic lipid molecules adsorb on the moderately hydrophobic surface and, thereby, greatly enhance its hydrophobicity. By virtue of the enhanced hydrophobicty, the water molecules adhering to the surface are destabilized and more readily removed during the process of mechanical dewatering. The moisture reduction can be further improved using appropriate electrolytes in conjunction with the lipids, spraying surface tension lowering reagents onto the filter cake, subjecting the cake to a suitable vibratory means, and using combinations thereof.

Abstract: Described are various human growth hormone releasing factor-PEG conjugates as well as their pharmaceutical use.

Abstract: The invention relates to fibrin/fibrinogen binding conjugate comprising a fibrin/fibrinogen binding moiety, a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance, and a pharmaceutically active substance, wherein the fibrin/fibrinogen binding moiety is bound to the substance capturing moiety, a kit for forming a depot for a pharmaceutically active substance and a method for producing a depot for a pharmaceutically active substance.

Abstract: This invention provides efficient methods for producing a covalent linkage having improved chemical stability between an amine-containing biomolecule and a solid support or hydrogel surface containing an aldehyde moiety.

Abstract: The present invention is directed to a composition for causing photodynamic damage to target cells comprising a photosensitiser, a photosensitiser carrier component, a component which enables target cell recognition and transport of the photosensitiser toward the interior of the target cell by specific receptor-mediated endocytosis, and a component capable of effective targeted transport of the photosensitiser within the target cells. The invention is also related to a method for causing photodynamic damage to target cells comprising the steps of: adding the composition to the cells; keeping the cells at a temperature of normal vital activity of cells with the composition for causing photodynamic damage to the target cells, said composition comprising the above-mentioned components; and exposure of the cells to light.

Abstract: Modified toxins including botulinum toxin or tetanus toxin coupled to polyethylene glycol, pharmaceutical compositions of modified toxins, and methods for their use are provided. The methods include treating inappropriate muscle contraction, and treatments for cosmetic purposes.

Abstract: A hedgehog conjugate which is characterized in that it contains: a) a polypeptide composed of 10 to 30 hydrophobic amino acids and/or amino acids which form transmembrane helices and are positively charged, b) 1 to 4 aliphatic, saturated or unsaturated hydrocarbon residues with a chain length of 10 to 24 C atoms and with a hydrophobic action or c) a hydrophobic thio compound covalently bound to a hedgehog protein and which has a several-fold increased activity and is suitable as a pharmaceutical agent.

Abstract: The present invention features biarsenical molecules. Target sequences that specifically react with the biarsenical molecules are also included. The present invention also features kits that include biarsenical molecules and target sequences. Tetraarsenical molecules are also featured in the invention.

Abstract: A composition for transdermal administration of a cytokine is described. The composition includes a conjugate composed of a cytokine, such as an interferon, and at least one fatty acid moiety covalently attached to the cytokine. The conjugate has enhanced cutaneous delivery relative to the cytokine alone.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: Chemically-defined, non-polymeric valency platform molecules and conjugates comprising chemically-defined valency platform molecules and biological or chemical molecules including polynucleotide duplexes of at least 20 base pairs that have significant binding activity-for human lupus anti-dsDNA autoantibodies.

Abstract: The present invention relates to conjugates, comprising an active substance, a polypeptide and a polyether, a process for the production of such conjugates as well as their use.

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: A method for selective labeling of phosphate groups in natural and synthetic oligomers and polymers in the presence of chemically related groups such as carboxylic acid groups. The method is specifically applicable to biological oligomers and polymers, including phosphopeptides, phosphoproteins and phospholipids. In a specific embodiment, selective labeling of phosphate groups in proteins and peptides, for example, facilitates separation, isolation and detection of phosphoproteins and phosphopeptides in complex mixtures of proteins. Selective labeling can be employed to selectively introduce phosphate labels at phosphate groups in an oligomer or polymer, e.g., in a peptide or protein. Detection of the presence of the label, is used to detect the presence of the phosphate group in the oligomer or polymer. The method is useful for the detection of phosphoproteins or phosphopeptides.

Abstract: There can be provided a fungal antigen which is an insoluble fraction obtainable from fungal cells of which cell wall has been substantially removed or at least partially removed; a process for producing the same; a nucleic acid encoding the fungal antigen; a biologic product containing the fungal antigen; a method of stimulating immunological responses by using the biologic product; a method of suppressing allergic reaction to fungi in a vertebrate; and a method for diagnosing a disease caused by fungi in a vertebrate.