Abstract: A compound of the formula: wherein R1 is selected from H, methyl, ethyl, carboxyl protecting groups and hydrophilic moieties, R2 and R3 are independently selected from H, methyl, ethyl and carboxyl protecting groups, R4 is selected from H, methyl, ethyl, hydrophilic moieties and carboxyl protecting groups, and R5 is an aryl, heteroaryl, alkyl or a combination of these groups and is substituted with a carbonyl group, an aminooxy group or a functional group suitable for participating in a cycloaddition reaction. The compounds of the invention may be useful as bifunctional chelating agents which allow chemoselective attachment to targeting molecules.

Abstract: The invention relates to methods for the production of polymer carrier materials for solid phase synthesis, particularly for peptide synthesis. (Meth)acrylamide derivatives based on carbon hydrates, which can also contain other protective groups, are polymerized by means of suspension polymerization in an aqueous phase, optionally with the addition of pore-forming additives, and subsequently the protective groups are fully or partially cleaved. It is thus possible to obtain polymer carriers whose morphology (particle size, porosity), degree of cross-linking and swelling capability in aqueous and organic media can be adjusted in a targeted manner and whose reactive groups offer multiple opportunities for the immobilization of anchor groups and protective groups. The hydroxyl groups of the polymer carrier can be activated according to usual methods of solid phase synthesis.

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 invention relates to HSP90 inhibiting compounds consisting of the formula: wherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Abstract: Processes for the synthesis of lipochitooligosaccharides were developed. A fully acylated oligoglucosamine precursor is prepared and reacted with a glucosamine monomer that has an amine protecting phthaloyl group. With removal of the phthaloyl group, a fatty acid may be added on the terminal glucosamine unit, forming a lipochitooligosaccharide. The processes can be adapted for use on a commercial scale.

Abstract: Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and 3?-position, their bioconjugates and their uses are described. 1,3?-crosslinked carbocyanines are superior to those of conjugates of spectrally similar 1,1?-crosslinked or non-crosslinked dyes. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: An inventive substrate is provided which includes a substrate compound of formula A-B1-B2-B3-B4: wherein A is a sugar moiety; B1 is a linker moiety allowing the conjugation of moiety A and the remaining structure of the substrate; B2 is a linker moiety with a free reactive amino group so as to be available for reaction with carboxylic acids or detectable tags; B3 contains a permanently charged element such as a quaternary ammonium group so as to increase sensitivity for mass spectrometry analysis; and B4 of various carbon length conferring specificity amongst individual substrates in detection methods. Also provided is a molecule of the formula B1-B2-B3-B4, with similar structural characteristics to an enzymatic product produced by the action of a target enzyme on an inventive substrate. Further provided are methods for using inventive substrates for detecting enzymatic activity.

Abstract: The invention provides compounds of Formula I: as described herein, as well as pharmaceutical compositions comprising the compounds, and synthetic methods and intermediates that are useful for preparing the compounds. The compounds of Formula (I) are useful as anti-viral agents and/or as anti-cancer agents.

Abstract: This invention relates to compounds that are analogues of coformycin, pharmaceutical compositions containing the compounds, and methods of using the compounds for treating protozoan parasite infections, especially malaria.

Abstract: The present invention relates to the method for tagging of carbohydrates with active methylene compound. Particularly, it relates to the method for tagging of carbohydrates with active methylene compound comprising the step of preparing carbohydrate conjugate in which carbohydrate and methylene compound are combined by mixing carbohydrate mixture and methylene compound under aqueous polar aprotic solvent containing amine base catalyst. The tagging method of the present invention does not need many kinds of chemical reagent and the reactions can be taken even in the presence of certain amount of impurities. So, it can be used for the analysis of oligosaccharide present in the various kinds of samples.

Abstract: New chelating agents as well as their tricarbonyl complexes with technetium and rhenium and the use of these compounds in radiodiagnosis and radiotherapy are described. As a peculiarity of this invention, synthesis and coupling of the chelating systems to (bio)molecules is performed simultaneously. The new chelating agents are coupled to substances that accumulate in the diseased/targeted tissue.

Abstract: The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

Abstract: Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.

Abstract: Adenoviral infections and in particular ocular adenoviral infections, e.g. keratoconjunctivitis, can be treated or alleviated by the administration of a substance, interfering with the interaction between the virus and the sialic acid receptor, in a therapeutically effective amount.

Abstract: The present invention relates to C-Glycosylisoflavones having alkylaminoalkoxyl substituent and pharmaceutically acceptable salts thereof, a process for the preparation thereof, pharmaceutical compositions comprising an effective amount of a compound of the formula (I), and to the use of these compounds or compositions for the treatment or prevention of cardio- and cerebrovascular diseases, in particular for the treatment of various cardiocerebral hypoxic-ischemic diseases, for the treatment or prevention of diabetes mellitus and complications thereof, and for the treatment or prevention of chemical poisoning, in particular alcoholism.

Abstract: The present invention generally relates to tetrahydropyranyl-derivatized amino acids, their syntheses and their incorporation into peptides and peptidomimetics. The tetrahydropyran moiety constrains the side chain of an amino acid, thereby providing a molecule that may act as a sugar- or amino acid-mimetic as well as a scaffold for combinatorial synthesis.

Abstract: The present disclosure relates to a method for metabolic oligosaccharide engineering that incorporates derivatized alkyne-bearing sugar analogs as “tags” into cellular glycoconjugates. The disclosed method incorporates alkynyl derivatized Fuc and alkynyl derivatized ManNAc sugars into a cellular glycoconjugate. A chemical probe comprising an azide group and a visual probe or a fluorogenic probe is used to label the alkyne-derivatized sugar-tagged glycoconjugate. In one aspect, the chemical probe binds covalently to the alkynyl group by Cu(I)-catalyzed [3+2] azide-alkyne cycloaddition and is visualized at the cell surface, intracellularly, or in a cellular extract. The labeled glycoconjugate is capable of detection by flow cytometry, SDS-PAGE, Western blot, ELISA or confocal microscopy, and mass spectrometry.

Abstract: The inventive molecular transporter compound shows significantly high permeability through a biological membrane such as a plasma membrane, nuclear membrane and blood-brain barrier, and accordingly, can be effectively used in delivering various biologically active molecules.

Abstract: The present invention relates to a process for the production of cross-linked hyaluronic acid (HA) derivatives, in particular multiple, e.g. double cross-linked hyaluronic acid derivatives. The invention also provides novel cross-linked HA derivatives, products containing them and their uses in medical and pharmaceutical and cosmetic applications.

Abstract: An asparagine-linked ?2,3-oligosaccharide having undeca- to hepta-saccharides, an asparagine-linked ?2,6-oligosaccharide having undeca- to hepta-saccharides and containing fluorine and an asparagine-linked oligosaccharide derivative containing at least one fucose in N-acetylglucosamine on the nonreducing terminal side of an asparagine-linked oligosaccharide wherein the asparagine has amino group protected with a lipophilic protective group, and a process for producing these compounds.

Abstract: The present invention provides oral formulations of Sulodexide for the treatment of diabetic nephropathy in patients with both insulin dependent and non-insulin dependent diabetes mellitus. Oral formulations containing doses adapted for administration to obtain a reduction in albumin excretion in patients with both micro and macro albuminuria and to produce lasting improvement in albumin excretion rate are provided. Methods of treating diabetic nephropathy using these formulations are also provided.

Abstract: A method for treating a cancer. The cancer excluding an adenocarcinoma and being epithelioma, glioma, sarcoma, melanoma, lymphoma or leukemia; or the cancer is an adenocarcinoma cancer excluding colon cancer, lung cancer and gastric cancer. The method comprises administering to a subject in need thereof and suffering from cancer, a pharmaceutically effective amount of at least one sulfoquinovosylacylglycerol compound represented by formula (1): wherein R101 represents an acyl residue of an unsaturated fatty acid and R102 represents a hydrogen atom and/or at least one pharmaceutically acceptable salt thereof.

Abstract: Described is a deliverable composition with low toxicity comprising an amphipathic compound, a polycation, and a siRNA. The composition may be used in the process of delivering a siRNA to an animal cell or more particularly, a mammal cell.

Abstract: This invention relates to substituted fused heterocyclic C-glycosides, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of diabetes and Syndrome X.

Abstract: The invention provides micelles, pharmaceutical formulations comprising micells, solutions comprising micells, methods for preparing micells, methods for delivering micells to patients, and methods for treating sepsis, endotoxemia, septic shock and systemic inflamatory response syndrome in patients by adiministering micelles. The micelles comprises compounds of Forumala (A): wherein the substituents are as defined herein.

Abstract: The present invention relates to biscarbodiimides, thiourea derivatives, urea derivatives, and cross-linked hyaluronan derivatives having at least one intramolecular disulfide bond, and methods of preparation thereof. The invention also includes thiolated hyaluronan derivatives and salts thereof having at least one pendant thiol group or a modified pendant thiol group, and methods of preparation thereof. An example of a modified pendant thiol group is a sulfhydryl group linked to a small molecule such as a bioactive agent, for example a drug or pharmaceutically active moiety. A hyaluronan derivative having a sulfhydryl group linked to a pharmaceutically active moiety is useful as a sustained or controlled release drug delivery vehicle. Compositions containing the hyaluronan derivatives of the invention can reversibly viscosify in vivo or in vitro, in response to mild changes in condition, and are thus useful in ophthalmic surgery and in tissue engineering.

Abstract: Biomaterials are disclosed comprised of biodegradable, biocompatible, and bioabsorbable non-woven fabric materials for use in surgery for the guided regeneration of tissues. The non-woven fabric materials are comprised of threads embedded in a matrix, wherein both the matrix and the threads can be comprised of esters of hyaluronic acid, used singly or in combination, or esters of hyaluronic acid in combination with esters of alginic acid or other polymers.

Abstract: The geometric isomers of olefins and olefinic compounds are separated by means of liquid chromatography using a stationary phase comprising an organosilane with a pendant aliphatic functional group such as C18 and a mobile phase which includes an additive comprising alkanes and alkenes.

Abstract: A medicament containing at least one compound selected from the group consisting of compounds represented by General formula (1): wherein R101 represents an acyl residue of an unsaturated higher fatty acid, and R102 represents a hydrogen atom or an acyl residue of an unsaturated higher fatty acid, and pharmaceutically acceptable salts thereof, as an active ingredient.

Abstract: New biomaterials essentially constituted by esterified derivatives of hyaluronic acid or by cross-linked derivatives of hyaluronic acid for use in the surgical sector, particularly for use in the prevention of post-surgical adhesion.

Abstract: Methods for treating diseases or conditions modulated or ameliorated by nitric oxide, particularly ischemia and reperfusion injury, are provided, using glycolipids structurally related to monophosphoryl lipid A but with notable reduction in proinflammatory and pyrogenic activity.

Abstract: The present invention relates to a composite sponge wound dressing and method for producing the same. Chitosan and &bgr;-Chitin is mixed in a specific ratio for forming the sponge for wound repairing. Particularly, when said ratio is between 0.1˜1, the composite sponge wound dressing has a better absorption and tensile strength.

Abstract: A method of making a derivatized aminoglycoside includes reacting an aminoglycoside with at least 2 equivalents of a divalent metal ion in an aprotic solvent to complex two neighboring amino group and hydroxyl group pairs; reacting the non-complexed amino groups with a protecting reagent to provide protecting groups; removing the divalent metal ion to provide two unprotected amino groups; reacting one of the unprotected amino groups with a reactive substance containing an linker, a carrier, or a label; and removing the protecting groups. This method can be used to produce novel compounds and reagents.

Abstract: This present invention provides a class of gene transfection reagents, which have a structure containing a nucleic acid binding domain and sugar targeting domain. The compounds are easy to synthesize and formulate. The formulated compound associates with DNA to form small particles with nearly neutral surface charge. The sugar domain plays a role as a tissue target ligand located on the surface of the nucleic acid complex, which promotes the receptor-mediated gene transfection. In the presence of proteins, these DNA complexes do not bind with proteins to form precipitates. The complexes are also stable when stored at 4° C. for a long time.

Abstract: The present invention relates to biscarbodiimides, thiourea derivatives, urea derivatives, and cross-linked hyaluronan derivatives having at least one intramolecular disulfide bond, and methods of preparation thereof. The invention also includes thiolated hyaluronan derivatives and salts thereof having at least one pendant thiol group or a modified pendant thiol group, and methods of preparation thereof. An example of a modified pendant thiol group is a sulfhydryl group linked to a small molecule such as a bioactive agent, for example a drug or pharmaceutically active moiety. A hyaluronan derivative having a sulfhydryl group linked to a pharmaceutically active moiety is useful as a sustained or controlled release drug delivery vehicle. Compositions containing the hyaluronan derivatives of the invention can reversibly viscosify in vivo or in vitro, in response to mild changes in condition, and are thus useful in ophthalmic surgery and in tissue engineering.

Abstract: The present invention relates to pharmaceutical compositions containing as an active ingredient at least one oligosaccharide of formula: to novel oligosaccharides of formula (I), to mixtures thereof and to methods for their preparation.

Abstract: The subject invention relates to monovalent oligosaccharides and their use, for example, in the treatment and prevention of mammalian disease caused by infection with Shiga toxin (ST) or Shiga-like toxin (SHL). In particular, the trisaccharide globotriose (i.e., galactose &agr;1,4 galactose &bgr;1,4 glucose) may be used to competitively inhibit binding of the toxins to their cellular targets.

Abstract: The invention is a degradable polyurethane resin obtained by reacting 2,5-/2,6-diisocyanatomethylbicyclo[2.2.1]heptane and/or a modified compound thereof with polyol comprising a single compound, mixture or copolycondensate selected from the group consisting of (A) polyhydroxycarboxylate polyol, (B) aliphatic polyester polyol and (C) saccharides, or (D) straight or branched polyol formed by condensation of (A) and/or (B) with aliphatic polyhydric alcohol having functionality of three or more, and the polyurethane resin has hydralyzability and biodegradability, is excellent in rigidity and elasticity in combination with flexibility as compared with conventionally known biodegradable resin, and can provide formed articles having outstandingly high elasticity and elongation and other unprecedented properties.

Abstract: Disclosed is a method for preparing a malto-oligosaccharide derived glycoside. Generally, the method comprises providing a malto-oligosaccharide and glycosylating the malto-oligosaccharide with an alcohol or a thiol under conditions suitable to form a malto-oligosaccharide derived glycoside. Also disclosed is a method for preparing a mixture of malto-oligosaccharide derived glycosides by providing a mixture of malto-oligosaccharides and glycosylating the malto-oligosaccharides with an alcohol or a thiol under substantially anhydrous conditions to form a mixture of malto-oligosaccharide derived glycosides.

Abstract: A compound of formula (I) below, which exhibits excellent macrophage activity inhibitory action, is useful for the treatment or prophylaxis of inflammatory disorders, autoimmune diseases or septicemia. In a preferred embodiment, R1 and R3 each represents a C1-C20 alkanoyl group which may optionally be substituted with one or more substituent groups selected from substituent group A, R2 and R4 each represents a C1-C20 alkyl group which may optionally be substituted with one or more substituent groups selected from substituent group A, R5 is a hydrogen atom, a halogen atom, a hydroxy group, or a C1-C6 alkoxy group, and substituent group A is a halogen atom, a hydroxy group, an oxo group, a C1-C20 alkoxy group, or a C1-C20 alkanoyloxy group.

Abstract: The invention provides novel glycosaminoglycan derivatives having a repeating unit structure of two saccharides of hexosamine and hexuronic acid as a backbone structure, in which the bonds between 2- and 3-positions carbon atoms of hexuronic acid as its constituting monosaccharide are partially cleaved and a part or all of the 2-position hydroxyl groups of uncleaved hexuronic acid are not substituted with a sulfate group, which has low anticoagulation activity and excellent neurite outgrowth promotion accelerating activity and sialidase inhibition activity; a process for producing the glycosaminoglycan derivatives, comprising a cleavage treatment of the bond between the 2- and 3-position carbon atoms of hexuronic acid having no sulfate group at the 2-position of glycosaminoglycan, and a selective desulfation treatment of the 2-position sulfate group of hexuronic acid; and a pharmaceutical composition comprising the glycosaminoglycan derivative as an active ingredient.

Abstract: Novel azo compounds and their bioconjugates for phototherapy and/or photodiagnosis of tumors and other lesions. The azo derivatives of the present invention are designed to absorb at the low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of free radicals, the reactive intermediate produced upon photoexcitation of the azo compound, with the tissue of interest.

Abstract: Disclosed is a chitosan microflake which is exceptionally improved in coatability to the skin. The chitosan microflake is manufactured by dissolving chitosan in a weak acidic, aqueous organic acid solution to give a chitosan solution, extracting chitosan from the solution, and solidifying the solution and pulverizing the form film into the microflake which has a width ten fold greater than thickness. With high coatability onto the skin, the chitosan microflake improves the medicinal efficacies of highly pure chitosan, including wound healing, sterilization, prevention or suppression of cicatrix formation, and recuperation from wounds, upon being applied to external traumas such as dermal damages, surgically operated regions and burns. In addition to the medicine and medical industries, the chitosan microflakes can find numerous applications in a broad spectrum of industries, including food, bioengineering, cosmetic, agricultural, chemical engineering, and environmental industries.

Abstract: Coumermycin analogs of general formula I: 1

Abstract: This invention utilizes methods of emulsion chemistry to derivative polymers, as distinguished from the synthetic methods of the prior art, whereby such polymers are derivative in a true solution. The derivative polymers are useful in that they may be readily reacted with small polymers or other molecules to form new polymeric entities. The new polymeric entities may be further derivative during the step of interracial dramatization, or may be provided for reaction to the product in a subsequent step to form the target product.

Abstract: A process for preparing polyvalent, physiologically degradable carbohydrate-containing polymers by enzymatic glycosylation reactions is described. The carbohydrate-containing polymers thus prepared may be used for preparing carbohydrate building blocks. The polyvalent carbohydrate-containing polymers of the invention cause no intolerance reactions in vivo, either in their intact form or in the form of degradation products. The carbohydrate side chain of the carbohydrate-containing polymer is assembled by enzymatic glycosylation reactions in homogeneous aqueous buffer systems directly on a biodegradable polymer. The yields of the glycosylation reaction are significantly improved over known processes, and are often quantitative. This also provides a significant increase in the loading densities. A process for preparing free oligosaccharides by means of the carbohydrate-containing polymers of the invention is also described.

Abstract: A method is provided for covalently linking carbohydrates, proteins, nucleic acids, and other biomolecules under neutral conditions, using a Diels-Alder cycloaddition reaction. In an example, activated carbon-carbon double bonds were attached to free amino sites of a carrier protein, and a conjugated diene was attached to a carbohydrate hapten. Spontaneous coupling of the carbohydrate and the protein components under very mild conditions provided glycoconjugates containing up to 37 carbohydrate hapten units per carrier protein molecule. The method is also applicable to the immobilization of biomolecules on gel or solid supports. The conjugated products are useful as immunogens and as analytical and diagnostic reagents.

Abstract: The invention concerns a novel phosphoglycolipid compound. The compound of the subject invention is 2-Deoxy-6-O-[2-deoxy-4-O-phosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-[(R)-3-octadecanoyloxytetradecanoylamino]-&bgr;-D-glucopyranosyl]-2-[(R)-3-hexadecanoyloxytetradecanoylamino]-D-glucopyranose and pharmaceutically acceptable salts thereof. The compound is not immunoreactive, not pyrogenic, not toxic but is active in ameliorating tissue damage due to ischemia/reperfusion injury. Methods for using the subject compound to protect against reversible and irreversible damage due to ischemia/reperfusion injury are also disclosed.

Abstract: Novel methods and compositions are provided for modulating homing of leukocytes, particularly lympho-cytes, where the compounds are cross-reactive with Neu5Ac2-3Gal&bgr;1-X[Fuc&agr;1-y]GlcNAc, where one of x and y is three and the other is four. These compounds may be administered to a host associated with inflammation, to avoid the deleterious effects of leukocyte infiltration and for directing molecules to such sites.

Abstract: A method is provided for covalently linking carbohydrates, proteins, nucleic acids, and other biomolecules under neutral conditions, using a Diels-Alder cycloaddition reaction. In an example, activated carbon-carbon double bonds were attached to free amino sites of a carrier protein, and a conjugated diene was attached to a carbohydrate hapten. Spontaneous coupling of the carbohydrate and the protein components under very mild conditions provided glycoconjugates containing up to 37 carbohydrate hapten units per carrier protein molecule. The method is also applicable to the immobilization of biomolecules on gel or solid supports. The conjugated products are useful as immunogens and as analytical and diagnostic reagents.