Abstract: Multi-use biosensors are disclosed that include enzymes that have been modified to reduce the solubility thereof; the multi-use biosensors are used to detect analytes in fluidic biological samples, and the biosensors also maintain their enzyme activity after many uses. Multi-sensor arrays are disclosed that include multiple biosensors. Also disclosed are methods of producing and using these devices.

Abstract: The present invention provides an aqueous pigment-material solution which has excellent thermal stability and less fading particularly even under an acidic condition, a method for producing the same, and a blue-colored beverage. Provided are an aqueous pigment-material solution including a pigment material containing 20 mmol to 200 mmol of polycarboxylic acid having one or more hydroxy groups, in terms of carboxylic acid equivalent, per 1 g of phycocyanin, in which when both the phycocyanin and the polycarboxylic acid are added such that a color value represented by absorbance at 620 nm is 2.5 to 5, an optical density per 1 cm of an optical path length at 800 nm is 0.05 or lower at a hydrogen ion concentration (pH) of 3 or lower, a method for producing the aqueous pigment-material solution, and a blue-colored beverage.

Abstract: The present invention relates generally to gene therapy for treating ailments that can affect vision such as retinal degeneration, retinal dystrophy, macular degeneration, macular dystrophy, ischemic retinopathies, and glaucoma. Embodiments include systems and treatments that use AAV-mediated gene therapy or non AAV-mediated DNA, mRNA, or protein therapy to target all retinal cells. An AAV virion can be introduced (e.g., via intravitreal or subretinal injection) into an eye of an individual, or systemically, to express a heterologous gene product such as BMI1 protein (B lymphoma Mo-MLV insertion region 1 homolog).

Abstract: The present disclosure relates to a third generation tubulysin analogues and process of preparation thereof. The present disclosure also relates to a method of using these third generation tubulysin analogues for treatment of various diseases including cancer.

Abstract: Engineered synthetic RNA-based genetic circuits are provided that are regulated exclusively at the post-transcriptional level.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. The mutant toxin may include a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to methods and compositions for use in culturing Clostridium difficile and in producing C. difficile toxins.

Abstract: Use of 2,4-dihalo-6-substituted-1,3,5-triazines as condensing, cross-linking, tanning, grafting, curing agents for the production of amides, esters, thioesters, and stabilized collagen and leather, CMC (carboxymethyl cellulose), synthetic and natural polymers. The process enables to obtain non-toxic and totally free of heavy metals products characterized by Tg values between 80° C. and 100° C.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. The mutant toxin may include a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to methods and compositions for use in culturing Clostridium difficile and in producing C. difficile toxins.

Abstract: The present invention relates to a TRIS- or neopentyl glycol-based amphipathic compound, a method of preparing the same, and a method of extracting, solubilizing, stabilizing, or crystallizing a membrane protein using the same. By using the TRIS- or neopentyl glycol-based compound according to the present invention, a superior membrane protein solubilization effect is exhibited, a membrane protein can be stably stored for a long time in an aqueous solution, and the structural fluidity of the membrane protein can be excellently maintained. Accordingly, the TRIS- or neopentyl glycol-based compound can be utilized in analyzing functions and structures of membrane proteins. Membrane protein structure and function analysis is currently one of the most attractive fields of research in biology and chemistry. Since more than half of the new drugs under development target membrane proteins, the compound can be applied to membrane protein structure research closely related to drug discovery.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

Abstract: A fluorescence molecular probe having a hydrophilic polypeptide backbone conjugated with a hydrophobic alkyl chain and a function group with aggregation induced emission is disclosed. The hydrophilic peptide sequence renders DNA binding capacity and the hydrophobic alkyl chain provides capacity for embedding within cell membrane. The aggregation induced emission renders real time tracking for live cell function studies. The synthesis of the probe is simple and easy for purification.

Abstract: Luminescent labels based on aromatic and heterocyclic compounds, including reactive intermediates used to synthesize these compounds, and methods of synthesizing and using these reporter compounds. These labels combine high photostabilities, large Stokes' shifts and contain a pyrimidinium moiety as a water-soluble group. These luminescent compounds relate generally to the following structure: The methods relate generally to the synthesis and/or use of reporter compounds for fluorescence lifetime or fluorescence polarization based applications.

Abstract: 1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate.

Abstract: The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.

Abstract: A phosphine derivative of DyLight dyes modified with ethylene glycol or (poly)ethylene glycol groups. In one embodiment, the compounds are useful in chemoselective ligation reactions.

Abstract: Disclosed are devices that comprise a protein, such as an antibody, placed into electronic communication with a semiconductor material, such as a carbon nanotube. The devices are useful in assessing the presence or concentration of analytes contacted to the devices, including the presence of markers for prostate cancer and Lyme disease.

Abstract: Disclosed is a bifunctional adapter molecule comprising two binding moieties A and B, the adapter molecule being capable of reversibly equipping a fusion protein carrying an oligohistidine affinity tag with a further affinity tag, wherein the binding moiety A comprises at least two chelating groups K, wherein each chelating group is capable of binding to a transition metal ion, thereby rendering moiety A capable of binding to an oligohistidine affinity tag, and the binding moiety B is an affinity tag other than an oligohistidine tag.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.

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: The invention provides a novel class of cyanine dyes that are functionalized with sulfonic acid groups and a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.

Abstract: Low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations for modifying biomolecules is provided. Compositions, methods, and kits relating to low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations are also provided.

Abstract: The invention is based on the discovery of the epitope in the Stx2 protein for the 11 E1O antibody. The invention features compositions containing non-full length Stx2 polypeptides that include the 11 E1O monoclonal antibody epitope. The invention also features methods of producing anti-Stx2 antibodies specific for the 11 E1O epitope of the Stx2 protein. Additionally, the invention features methods for treating a subject having, or at risk of developing, a Shiga toxin associated disease (e.g., hemolytic uremia syndrome and diseases associated with E. coli and S. dysenteriae infection) with a polypeptide that includes the 11 E1O epitope or with an anti-Stx2 antibody developed using the methods of the invention. Furthermore, the invention features the detection of Stx2 in a sample using the antibodies developed using the methods of the invention.

Abstract: Binder compositions are described, where the compositions include a protein, a first crosslinking compound that includes a carbohydrate, and a second crosslinking compound that includes two or more primary amine groups. The first and second crosslinking compounds may be individually crosslinkable with each other and with the protein. Also described are fiber products that may include inorganic or organic fibers and a cured thermoset binder prepared from a protein and at least two crosslinking compounds. Additionally, methods of making fiber products are described that include providing inorganic or organic fibers, and applying a liquid binder composition to the fibers to form a fiber-binder amalgam. The liquid binder composition may include a protein and at least two crosslinking compounds that include a carbohydrate and an organic amine with two or more primary amines. The amalgam may be heated to a curing temperature to form the fiber product.

Abstract: 1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate.

Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: The invention relates to the field of covalently attaching proteins to a substrate, particularly to methods of immobilizing proteins by posttranslationally modifying a cysteine residue of said protein through the addition of functional groups. The invention also relates to biological molecules used in such techniques, including proteins, and detection methods and kits that utilize such immobilized proteins, such as a microdevice or “protein chip”, a high-throughput screening device, and for the microscopy of proteins on a surface.

Abstract: Provided is a preparation method for phycocyanin, including: adding chitosan to a suspension of cyanobacteria containing phycocyanin; and filtering the suspension.

Abstract: A method of making a bacteriochlorin is carried out by condensing a pair of compounds of Formula II to produce the bacteriochlorin, wherein R is an acetal or aldehyde group. The condensing may be carried out in an organic solvent, preferably in the presence of an acid. The bacteriochlorins are useful for a variety of purposes such as active agents in photodynamic therapy, luminescent compounds in flow cytometry, solar cells, light harvesting arrays, and molecular memory devices.

Abstract: Provided herein are polymers having the general formula I as defined herein, A-L-B??Formula I as well as crosslinked polymers having the general formula III: B?-L?-A?-A?-L?-B???Formula III and methods of preparing the polymers, wherein A is a dihydroxyphenyl moiety; A?-A? is a pair of crosslinked dihydroxyphenyl moieties; B, B? and B? are each a biopolymer; and L, L? and L? are each a linking moiety. Further provided are crosslinked adhesives prepared from the polymers, methods of generating same by oxidizing a polymer, and uses thereof. Further provided are kits comprising an adhesive and an oxidizing agent.

Abstract: The present invention refers to methods and compositions to prevent viral entry into cells expressing the CD169/sialoadhesin surface receptor by inhibiting the coupling of the sialyllactose molecule contained in the viral membrane gangliosides to the CD 169/sialoadhesin receptor. The invention also pertains to vaccine compositions based on dendritic cells loaded with an antigen of interest whereby the vaccine is provided together with a composition capable of preventing viral entry into cells expressing the CD169/sialoadhesin. Moreover, the invention relates to diagnostic and therapeutic compositions that can be specifically delivered to enveloped virions wherein the diagnostic/therapeutic agent is coupled to CD169/sialoadhesin.

Abstract: The invention aims in establishing a method for modifying biomolecules using a reaction that efficiently modifies biomolecules and is widely applicable. The invention thus provides a cyclic compound containing two triazole rings formed by adding and ligating an azide compound possessing an azido group to each of the two carbon-carbon triple bond sites of an eight-membered cyclic skeleton of a cyclic diyne compound by a double click reaction; a method for producing a cyclic compound using a double click reaction; and a method for modifying biomolecules.

Abstract: Binder compositions are described, where the compositions include a protein, a first crosslinking compound that includes a carbohydrate, and a second crosslinking compound that includes two or more primary amine groups. The first and second crosslinking compounds may be individually crosslinkable with each other and with the protein. Also described are fiber products that may include inorganic or organic fibers and a cured thermoset binder prepared from a protein and at least two crosslinking compounds. Additionally, methods of making fiber products are described that include providing inorganic or organic fibers, and applying a liquid binder composition to the fibers to form a fiber-binder amalgam. The liquid binder composition may include a protein and at least two crosslinking compounds that include a carbohydrate and an organic amine with two or more primary amines. The amalgam may be heated to a curing temperature to form the fiber product.

Abstract: The invention pertains to a near-infrared fluorescent dye that is cell permeable and can be attached to selected proteins in living cells. The dye has the general formula or its corresponding spirolactone wherein Y is chosen from the group consisting of Si, Ge and Sn; R0 is —COO? or COOH; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 and R16 are substituents, including hydrogen, independently from each other. The dye (i) absorbs and emits light at wavelengths above 600 nm; (ii) possesses high photostability; (iii) has high extinction coefficients and high quantum yields; (iv) can be derivatized with different molecules; and (v) is membrane-permeable and shows minimal background binding to biomolecules and biomolecular structures.

Abstract: The invention concerns the generation of a three dimensional model of the six helix bundle (6HB) complexed with an inhibitor and the use of that model to identify, screen and/or develop inhibitors against viruses that use a class I fusion protein. Such inhibitors of viruses that use a class I fusion protein may be effective for treating, for example, respiratory infections by Respiratory Syncytial Virus (RSV).

Abstract: The present invention relates to a chromatography ligand defined by the following formula R1—R2—N(R3)—R4—R5 wherein R1 is a substituted or non-substituted phenyl group; R2 is a hydrocarbon chain comprising 0-4 carbon atoms; R3 is a hydrocarbon chain comprising 1-3 carbon atoms; R4 is a hydrocarbon chain comprising 1-5 carbon atoms; and R5 is OH or H. The invention also comprises a separation matrix, comprising the described ligands coupled to a porous support, such as particles or a membrane. The ligand and matrix according to the invention is useful for purification of biomolecules or organic compounds, such as proteins, polypeptides, DNA etc. An advantageous use according to the invention is the purification of antibodies.

Abstract: The invention provides calcium-binding photoproteins which can detect light emission with a higher sensitivity. The proteins of the invention comprising the amino acid sequence of SEQ ID NO: 2 can be used for the detection and measurement of calcium ions. The proteins of the invention are useful as reporter proteins, luminescent markers, etc. The polynucleotides of the invention are useful as reporter genes, etc.

Abstract: The present invention allows formation of covalent bonds in a bioactive compound having at least one amino group so as to efficiently provide the compound modified with PEG. The present invention thus provides a functionalized polyethylene glycol having a structure that allows reaction of two aldehyde groups with one amino group to form two covalent bonds.

Abstract: The invention provides amphiphiles for manipulating membrane proteins. The amphiphiles can feature carbohydrate-derived hydrophilic groups and branchpoints in the hydrophilic moiety and/or in a lipophilic moiety. Such amphiphiles are useful as detergents for solubilization and stabilization of membrane proteins, including photosynthetic protein superassemblies obtained from bacterial membranes.

Abstract: The present invention relates to water-soluble protein carrier-linked prodrugs wherein the protein carrier comprises an amino acid sequence consisting of at least 100 amino acid residues forming random coil conformation and comprising alanine, serine and proline residues. It further relates to pharmaceutical compositions comprising said water-soluble protein carrier-linked prodrugs, their use as a medicament as well as methods of treatment and administration.

Abstract: Methods are provided for a one step synthesis of polypeptide polymers or co-polymers. The polymers or co-polymers can be linear or branched. In the methods of the invention, the coding sequence for the polypeptide(s) to be polymerized is altered by introducing one or more codons for an nonnatural amino acid, which coding sequence is then utilized to produce the cognate polypeptide. The nonnatural amino acids are selected to be reactive with each other in a bioorthogonal reaction, and are combined in a conjugation reaction with the desired components of the polymer.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one aromatic amine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one alkylated amine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The object of the present invention is to provide a method for immobilizing the SpA protein on the surface of a substrate with high density without causing dimerization. The following method solves the object. That is, the method for binding a protein to a surface of a substrate, comprising steps (A) to (B): step (A) of preparing said protein to the surface, step (B) of supplying said protein to the surface, wherein said protein consists of a Protein A or at least one domain of A to E of said Protein A, and said protein comprises C-terminal modified amino acid sequence represented by SEQ ID:1(SFNRSEC).

Abstract: The embodiments of the invention relate to a method for the introduction of a labeling structure such as a fluorescent molecules or a Raman tags to a compound. Imidazole functionalized resins or polymers are used to selectively immobilize phosphocompounds without protecting the carboxylic groups. Relying on the pKa difference between amines and hydrazides and carrying out the reaction in a slightly acidic buffer, all of the amines are protected by protonation while the hydrazides react with the phosphate imidazolide to form a phosphoramidate bond.

Abstract: The present invention is directed to an inventive polymeric carrier molecule according to generic formula (I) and variations thereof, which allows for efficient transfection of nucleic acids into cells in vivo and in vitro, a polymeric carrier cargo complex formed by a nucleic acid and the inventive polymeric carrier molecule, but also to methods of preparation of this inventive polymeric carrier molecule and of the inventive polymeric carrier cargo complex. The present invention also provides methods of application and use of this inventive polymeric carrier molecule and the inventive polymeric carrier cargo complex as a medicament, for the treatment of various diseases, and in the preparation of a pharmaceutical composition for the treatment of such diseases.

Abstract: Described herein, at least in part, are methods of modulating oncogenic fusion proteins.

Abstract: Methods to introduce highly phosphorylated mannopyranosyl oligosaccharide derivatives containing mannose-6-phosphate (M6P), or other oligosaccharides bearing other terminal hexoses, to carbonyl groups on oxidized glycans of glycoproteins while retaining their biological activity are described. The methods are useful for modifying glycoproteins, including those produced by recombinant protein expression systems, to increase uptake by cell surface receptor-mediated mechanisms, thus improving their therapeutic efficacy in a variety of applications.

Abstract: A compound including a cell penetrating peptide (CPP), an elastin-like polypeptide (ELP), and a therapeutic peptide (TP) can be preferentially directed to a target site by applying hyperthermia. The compound can be useful for the treatment of tumors.

Abstract: This invention provides methods of making and using a fluorescent probe from the Sandercyanin protein as set forth in SEQ ID NO: 1 or SEQ ID NO: 2. In one embodiment, the invention provides a method of creating a fluorescent probe, comprising the steps of attaching a Sandercyanin moiety to a probe, wherein the probe is specific to a desired target.