Abstract: A process for producing coelenteramide or its analog in a high yield has been desired. The invention provides a process for producing di-O-methylcoelenteramide or its analog of formula (3) which comprises reacting O-methylcoelenteramine or its analog with 4-methoxyphenylacetyl halide or its analog. The invention also provides a process for producing coelenteramide or its analog, which comprises demethylation of di-O-methylcoelenteramide or its analog.

Abstract: The present invention provides novel osmium-based electrochemical species for the detection of wide variety of analytes using immunological techniques. The present invention also provides diagnostic kits and test sensors supporting electrode structures that can be used with the osmium-based electrochemical species. The test sensor can be fabricated to support interdigitated arrays of electrodes that have been designed to provide amplification of the electrical signal amplification desired to analyze analytes that may be present at low concentrations.

Abstract: An HA-protein conjugate in which an HA-aldehyde derivative, in which an aldehyde group is introduced to a hyaluronic acid or a salt thereof, is conjugated to the N-terminus of a protein, and a method for preparing the same are provided. The HA-protein conjugate includes a protein drug exhibiting an excellent bioconjugation efficiency and long-term medicinal effects, and has excellent protein drug activities since the hyaluronic acid is specifically conjugated to the N-terminus of the protein. Also, since liver-targeting properties of the hyaluronic acid can be freely controlled by changing an aldehyde substitution rate of the HA-aldehyde derivative, the HA-protein conjugate can be effectively used as a protein drug for treating liver diseases, and also be useful in enabling long-term medicinal effects of a protein drug required to bypass the liver. Accordingly, the HA-protein conjugate can be effectively used for a drug delivery system of proteins.

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 antibody compositions and use of the composition to detect disease processes associated with elaboration of proteases. The reagents are directed to assessing an IgG breakdown product that is the result of such proteolytic cleavage. The invention further relates to the use of a therapeutic immunospecific for IgG protease cleavage products to restore effector function to antibody compositions that are subject to protease cleavage.

Abstract: A novel type of particle platform for application in biotechnology is provided by the present invention. Said platforms comprise RNA-free particles generated by thermal denaturation and structural remodeling of helical plant viruses. Tobamovir-uses and, in particular, tobacco mosaic virus (TMV) coat protein (CP) subunits, denatured, at high temperatures are specifically self-assembled by two-stage assembly into the spherical particles (SPs) of similar shape and varying size including nanoparticles (SNPs) with a diameter up to 100-150 nm and spherical microparticles (SMPs) with a diameter up to 800 nm and more. The size of said SPs depends on the virus concentration used and, therefore can be controlled. Said SPs are biologically safe, highly stable and highly immunogenic. Said SNPs and SMPs are structurally distinct from viruses presently known. They are unique, having no protein nano-particle analogs in the nature.

Abstract: The present invention relates to reagents and methods for [18F]-fluorination of biomolecules, particularly of peptides. The resultant 18F-labelled compounds are useful as radiopharmaceuticals, specifically for use in Positron Emission Tomography (PET).

Abstract: Methods to produce keratin elastomer, involving: (A)(1) reacting a diisocyanate with a blocking agent to form a diisocyanate with one —NCO group blocked by the blocking agent and one —NCO group unblocked, (2) reacting the diisocyanate with one —NCO group blocked by the blocking agent and one —NCO group unblocked with keratin at about 100° to about 120° C. to form keratin urethane with —NCO group functionality (i.e., with one —NCO group unblocked), (3) optionally reacting the keratin urethane with —NCO group functionality with a compound capable of reacting with the —NCO group; (B) reacting a diisocyanate with keratin to form keratin elastomer; or (C) reacting a monoisocyanate with keratin to form keratin elastomer.

Abstract: The purpose is to produce, with high reproducibility, a complex of labeled probes and a carrier, said complex being to be used for detecting and measuring a target substance to be measured with high sensitivity and high stability. The means for accomplishing the purpose is that a label is bound to a probe-water soluble carrier conjugate using specific binding of an avidin compound such as avidin, streptavidin, etc. to biotin, and the binding of the avidin compound to the probe is performed before the binding to the carrier. Namely, after conjugating the avidin compound to a substance which is capable of binding to the target substance, the conjugate is bound to a high-molecule water-soluble carrier to produce a complex of the avidinized probes and the water-soluble carrier. Then the complex of the avidinized probes and the water-soluble carrier is mixed with a biotinylated label.

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 relates to radiodiagnostic and radiotherapeutic agents, including biologically active vectors labelled with radionuclides. It further relates to methods and reagents labelling a vector such as a peptide comprising reaction of a compound of formula (I) with a compound of formula (II): or, a compound of formula (III) with a compound of formula (IV) in the presence of a Cu (I) catalyst. The resultant labelled conjugates are useful as diagnostic agents, for example, as radiopharmaceuticals more specifically for use in Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) or for radiotherapy.

Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: The present invention relates to novel tubulysin compounds (tubulysin analogues) as well as pharmaceutical formulations thereof. The present invention further relates to the use of such compounds for medicinal, agricultural, biotool or cosmetic applications. In particular, the novel tubulysin analogues show a cytostatic effect and can therefore be used for the treatment of proliferative disorders. The tertiary amide moiety of the tubulysin analogues (so-called tubugis) according to the present invention is generated by an Ugi-type reaction.

Abstract: The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins, nucleic acids and cellular organelles. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified to provide beneficial properties.

Abstract: The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide that associates with (e.g., specifically binds to) the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that associate with (e.g., specifically bind to) neurons or nerves and for compositions thereof.

Abstract: One molecule of the amino acid selected from the five kinds of amino acids consisting of cysteine, lysine, histidine, phenylalanine, and glycine is interposed between a self-assembled monolayer and a molecule of a protein. A method for immobilizing an protein on a self-assembled monolayer includes the following steps (a) and (b) in this order: a step (a) of preparing a substrate including one molecule of an amino acid and the self-assembled monolayer and a step (b) of supplying the protein to the substrate to form a peptide bond represented by a predetermined chemical formula as a result of reaction between the carboxyl group of the one molecular of the amino acid and the amino group of the protein.

Abstract: Disclosed are targeted particles comprising or consisting of a plurality of landscape phage fusion proteins complexed with heterologous nucleic acid, the landscape phage fusion proteins displaying a heterologous peptide and the targeted particle binding specifically to a target site. The particles may be utilized in methods for modulating expression of genes in target cells.

Abstract: Peptides and methods of use thereof are provided.

Abstract: The present disclosure provides IDAC compounds capable of presenting two or more signal 1 moieties to a host immune system and methods of using the IDAC compounds to treat or prevent autoimmune disorders in a subject. The present disclosure provides compounds including a modified I-domain peptide having two or more modified lysine residues and two or more signal 1 moieities conjugated to the modified lysine residues of the I-domain peptide and methods of using an making the compounds.

Abstract: An immunogen includes an isolated peptide of 800 amino acid residues or fewer having the amino sequence ILSAFSVYV (SEQ ID NO:1) with four or fewer amino acid substitutions, a superagonist variant of SEQ ID NO:1, or an amino acid sequence having the formula: (I/K/T/V/M)-L-(S/L)-(A/E/N/D/Q)-(F/V)-(S/M/V/I)-(V/D/R/G/H)-Y-(V/I/L) (SEQ ID NO:13). The immunogens can be used in compositions and in the treatment of disorders.

Abstract: The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with posttranslational glycosylations. The methods can be used to detect O-GlcNAc posttranslational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engine˜red mutant of ?-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes.

Abstract: Compounds and methods are disclosed that are useful for noninvasive imaging in the near-infrared spectral range. The cyanine compounds of Formula I are presented: wherein Q is a portion of a polymethine bridge selected from the group consisting of: Also included are bioconjugates of the compounds of Formula I, methods of labeling biomolecules with the compounds, and methods of imaging.

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: GB1 peptidic compounds that specifically bind to a hemagglutinin target protein, and libraries that include the same, as well as methods of making and using the same, are provided. Also provided are methods and compositions for making and using the compounds. Also provided are hemagglutinin mimics and fragments and methods of using the same, including methods of screening for GB1 peptidic compounds and methods of using conjugates the mimics as influenza A vaccines. Aspects of the invention include methods of screening libraries of L-peptidic compounds for specific binding to a D-peptidic hemagglutinin target protein. Once a L-peptidic compound has been identified that specifically binds to the D-peptidic hemagglutinin target protein, the D-enantiomer of the selected L-peptidic compound may be produced. In some embodiments, the D-enantiomer of the selected L-peptidic compound binds to, and in some instances, neutralizes influenza virus particles.

Abstract: Fluorescent phenyl xanthene dyes are described that comprise any fluorescein, rhodamine or rhodol comprising a particular C9 phenyl ring. One or both of the ortho groups on the lower C9 phenyl ring is ortho substituted with a group selected from alkyl, heteroalkyl, alkoxy, halo, haloalkyl, amino, mercapto, alkylthio, cyano, isocyano, cyanato, mercaptocyanato, nitroso, nitro, azido, sulfeno, sulfinyl, and sulfino. In one embodiment, halo and/or hydroxy groups are used. Optimal dyes contain a lower C9 phenyl ring in which both ortho groups are the same and the lower ring exhibits some form a symmetry relative to an imaginary axis running from the phenyl rings point of attachment to the remainder of the xanthene dye through a point para to the point of attachment. The phenyl xanthene dyes may be activated. Furthermore, the phenyl xanthene dyes may be conjugated to one or more substances including other dyes.

Abstract: A method for enhancing a luminescence activity of clytin-II is provided. A codon-optimized nucleic acid is used for coding the apo-clytin-II protein, and the luminescent activity of the clytin-II is remarkably enhanced when comparing with the conventional use of the wild-type clytin-II.

Abstract: Methods for preparing conjugates including enzyme conjugates and especially alkaline phosphatase (ALP) conjugates, and a kit are provided. The methods include: blocking an amino group on a molecule surface of a first substance to be conjugated containing an amino group and a carboxyl group (for example, an enzyme) with a carboxyl compound; adding a carbodiimide to activate the first substance to be conjugated with the amino group blocked; inactivating or removing the carbodiimide; and adding a second substance containing an amino group (for example, a substance to be labeled). Conjugates (for example, enzyme conjugates) are obtained.

Abstract: The present invention is related to a nucleic acid molecule capable of binding to a lipid.

Abstract: The invention relates to intracellular lipid binding proteins that bind retinoids and/or dye ligands and that are modified to transmit or emit light at a variety of different wavelengths.

Abstract: A modified G-protein-coupled receptor (GPCR), having modified ligand affinity is provided by binding a G-protein-coupled receptor to a polypeptide consisting of an amino acid sequence of SEQ ID NO: 1. Furthermore, agonists for or antagonists against the modified GPCR are screened using a transformant in which the modified GPCR has been expressed. This makes it possible to provide a technique for analyzing the function of many putative GPCRs whose entities have not been clarified.

Abstract: The present invention provides compounds, compositions, and methods for detecting, diagnosing and treating cancers such as glioblastoma multiforme.

Abstract: Disclosed herein is a composition and method for sample preparation of proteins for their size separation by electrophoresis, suitable for molecular-weight determination of proteins in the range between about 14,000 and 500,000. In an embodiment, proteins, particularly those exhibiting biased migration, are modified to change their intrinsic charge, or carbohydrate component to improve accuracy of their molecular weights as determined by electrophoretic size separation via their interaction with ionic surfactants. In a preferred embodiment, the proteins are carbamylated with potassium cyanate and their carbohydrate components are oxidized with sodium periodate.

Abstract: The present invention relates to the use of a peptide consisting of 5 to 30 amino acid residues comprising an amino acid sequence selected from LLADTTHHRPWT (SEQ ID NO: 1), SPGLSLVSHMQT (SEQ ID NO: 2), and the sequences presenting at least 80% identity with SEQ ID NO: 1 or SEQ ID NO: 2, for the funcfionalization of silicon substrate. The present invention also relates to the specific peptides as such, and to silicon substrates functionalized by the adsorption on their surface of such specific peptides. Finally, the present invention is also directed to a process for the preparation of such functionalized silicon substrates, and to articles comprising a silicon substrate according to the invention.

Abstract: Synthesis of many proteins is tightly controlled at the level of translation and plays an essential role in fundamental processes such as cell growth and proliferation, signaling, differentiation or death. Methods that allow imaging and identification of nascent proteins allow for dissecting regulation of translation, both spatially and temporally, including in whole organisms. Described herein are robust chemical methods for imaging and affinity-purifying nascent polypeptides in cells and in animals, based on puromycin analogs. Puromycin analogs of the present invention form covalent conjugates with nascent polypeptide chains, which are rapidly turned over by the proteasome and can be visualized and specifically captured by a bioorthogonal reaction (e.g., [3+2]cycloaddition). The methods of the present invention have broad applicability for imaging protein synthesis and for identifying proteins synthesized under various physiological and pathological conditions in vivo.

Abstract: Bis-diazo, triaryl and aryldiazo-N-arylphenazonium quencher moieties, substituted with electron-withdrawing and electron-donating substituents which induce polarity in the delocalized aryl/diazo ring systems, are useful as labels when attached to biomolecules such as polynucleotides, nucleosides, nucleotides and polypeptides. The quencher moieties are non-fluorescent and accept energy transfer from fluorescent reporter labels by any energy-transfer mechanism, such as FRET. Fluorescence quencher compositions are useful in preparing quencher labeled biomolecules for various molecular biology assays based on fluorescence detection.

Abstract: Processes are provided for recovering and purifying refolded recombinant proteins produced in heterologous host cells, which includes the step of refolding the protein in a high pH buffer.

Abstract: The present invention provides dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins, nucleic acids and cellular organelles. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes provided in this invention can comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been substituted with specific groups to provide beneficial properties.

Abstract: The present invention relates in general to labeling reagents useful for labeling biomolecules. In particular, the invention provides activated labeling reagents having the formula L-Ph, wherein L is an activated labeling molecule and Ph is a phenol. The invention further provides methods of preparing the labeling reagents, methods of using the labeling reagents for synthesizing a labeled biomolecule, kits that include reagents for labeling a biomolecule and kits containing labeled biomolecules.

Abstract: A modular platform is provided for rapid preparation of various water-soluble prosthetic groups capable to efficiently introduce 18F into proteins with 18F labelling reagents.

Abstract: Disclosed are agents and methods that may be used to diagnose and treat a variety of diseases associated with conformationally-altered proteins. The agents and methods may be used to identify and deliver drugs useful for treating diseases associated with conformationally-altered proteins.

Abstract: There has been a need for coelenteramide analogs or the like that produce fluorescent proteins which exhibit different fluorescent characteristics from those of the existing fluorescent proteins. Disclosed is a compound represented by general formula (1) (wherein R1 represents a substituted or unsubstituted aryl, a substituted or unsubstituted arylalkyl, a straight or branched alkyl which may optionally be substituted with an alicyclic group, an alicyclic group or a heterocyclic group; R2 represents hydrogen or —(SO2)R4; R3 represents hydrogen, hydroxyl, methoxy or acetoxy; R4 represents a substituted or unsubstituted aryl, a substituted or unsubstituted arylalkyl or a straight or branched alkyl which may optionally be substituted with an alicyclic group; and X1 represents —C(?S)— or —SO2—).

Abstract: The present invention relates to peptides and antibodies which bind to melanoma inhibitory activity protein and the uses of such peptides and antibodies. The invention also relates to nucleic acids coding for such peptides or antibodies. The invention also relates to pharmaceutical compositions comprising such peptides or antibodies or such nucleic acids. The present invention also relates to small molecule compounds which bind to melanoma inhibitory activity protein and to uses of such small molecule compounds. Moreover, the present invention also relates to a method of preventing dimerization and/or aggregation of melanoma inhibitory activity (MIA) protein. The invention is based on the identification of the relevant sites of interaction of the MIA protein with the inhibitory peptides/antibodies.

Abstract: A molecular construct comprises a donor label, an acceptor label, a linker peptide disposed between the donor and the acceptor, the linker having a cleavage site sequence, and a spacer between at least one of (a) the donor and the cleavage site sequence and (b) the acceptor and the cleavage site sequence. Preferably, the construct is selected from the group consisting of CFP-(SGLRSRA)-SNAP-25-(SNS)-YFP, and CFP-(SGLRSRA)-synaptobrevin-(SNS)-YFP. In preferred embodiments, the linker peptide is a substrate of a botulinum neurotoxin selected from the group consisting of synaptobrevin (VAMP), syntaxin and SNAP-25, or a fragment thereof that can be recognized and cleaved by the botulinum neurotoxin. Advantageously, the spacer increases the electronic coupling between the donor label and the acceptor label relative to a corresponding construct without the spacer.

Abstract: Derivatives of PSAs are synthesised, in which a reducing and/or non-reducing end terminal sialic acid unit is transformed into a N-hydroxysuccinimide (NHS) group. The derivatives may be reacted with substrates, for instance substrates containing amine or hydrazine groups, to form non-cross-linked/crosslinked polysialylated compounds. The substrates may, for instance, be therapeutically useful drugs, peptides or proteins or drug delivery systems.

Abstract: Provided are various compounds comprising the formula Also provided are fluorescent dyes comprising the above compound. Additionally, a fluorescence energy transfer system is provided that comprises the above-described fluorescent dye and a second dye, wherein the second dye is capable of energy transfer with the fluorescent dye. Further provided is a kit for labeling a target molecule, where the kit comprises the above-described fluorescent dye with additional reagents useful for labeling the target molecule. Additionally provided is a target molecule labeled with the above-described fluorescent dye. A method of labeling a target molecule is also provided. The method comprises contacting reactive group Z of the above-described fluorescent dye with the target molecule such that reactive group Z reacts with the target molecule to form a covalent bond between reactive group Z and the target molecule. Also, another method of labeling a target molecule is provided.

Abstract: The present invention relates to biosensors. In some embodiments, the biosensors are modified ligand binding molecules. In some embodiments, the modified ligand binding molecule is a phosphate binding protein (PBP). In some embodiments, the modified ligand binding molecules are labeled to be capable of RET, e.g., comprising a donor and acceptor moiety. In some embodiments of the invention, there is a detectable change in RET (e.g., FRET) when the modified ligand binding molecule binds and/or releases the ligand (e.g., phosphate). The invention also provides related methods, reactions and assays.

Abstract: Benzodiazepine compounds, pharmaceutical compositions containing such compounds and to their use in therapy.

Abstract: A flexible method for making multiplexed assays for antigen-specific antibody responses is disclosed herein. The method of the present invention comprises incubation of a substrate or a set of beads coated with a dockerin or a cohesin protein with a cohesin or dockerin-antigen fusion proteins to attach the fusion protein essentially irreversibly by non-covalent interaction. The present invention enables the use of one dockerin- or cohesin-coated bead for multiple sets of cohesin- or dockerin-antigens, obviating the need to directly chemically couple new antigens to new beads.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties.