Abstract: The invention relates to compositions of vault complexes containing recombinant membrane lytic proteins, such as an adenovirus protein VI lytic domain, and methods of using the vault complexes to facilitate delivery and entry of a biomolecule into a cell or subject.

Abstract: Provided are methods and compositions for selectively targeting CRKL through the use of targeting peptides. Selective targeting of secreted CRKL through the use of a targeting peptide may be used, for example, in the treatment of cancer to deliver a chemotherapeutic compound, fusion protein, or fusion construct to a cancer cell or tissue.

Abstract: A complex comprising at least one target protein and at least one binding molecule having a binding affinity for said target protein, wherein said molecule having a binding affinity is covalently or non-covalently bound to at least one water-soluble polymer

Abstract: The application concerns an isolated protein complex comprising polypeptide components: (i) UTP20 HUMAN or a fragment, variant or homologue thereof; (ii) PWP2 HUMAN or a fragment, variant or homologue thereof; (iii) WDR46_HUMAN or a fragment, variant or homologue thereof; (iv) UTP18 HUMAN or a fragment, variant or homologue thereof; (v) MPPIO HUMAN or a fragment, variant or homologue thereof; (vi) WDR3_HUMAN or a fragment, variant or homologue thereof; (vii) TBL3 HUMAN or a fragment, variant or homologue thereof; (viii) WDR36_HUMAN or a fragment, variant or homologue thereof; and (ix) N0C4L HUMAN or a fragment, variant or homologue thereof.

Abstract: This invention pertains to the surprising discovery that salicylanilides, e.g., niclosamide and/or niclosamide analogues can be reacted with a therapeutically active peptide to produce a modified peptide complex that shows increased resistance to proteolysis and that shows higher bioactivity when orally administered than the unmodified peptide.

Abstract: A molecular sensor is provided that contains at least one carbon nanotube suspended on a suitable support structure. In one aspect, at least one receptor is attached to a surface of the suspended carbon nanotube. Also provided are methods of detecting an analyte in a sample by contacting a sample suspected of containing the analyte with the molecular sensor of this invention under suitable conditions that favor binding of the analyte to the receptor and detecting any analyte bound to the receptor, if present.

Abstract: The invention describes the use of particular cross-linking reagents containing 1-hydroxybenzotriazole or 1-hydroxy-7-azabenzotriazole groups as reactive groups for cross-linking reactions of supramolecular target-ligand-complexes. The resulting cross-linked products may be directly analyzed using mass spectrometry, gel or fluorescence based technologies, X-ray crystallography, NMR or other analytical technologies. The method using High-Mass MALDI mass spectrometry provides various biological applications such as characterization of antibodies, drug discovery, and protein complex analysis including automated or higher throughput applications.

Abstract: The present invention provides a protein having chain of a ricin-like toxin, a B chain of a ricin-like toxin and a novel heterologous linker amino acid sequence, linking the A and B chains. The linker sequence contains a cleavage recognition site for a specific protease such as those found in inflammatory cells and cancer cells. The invention also relates to a nucleic acid molecule encoding the protein and to expression vectors incorporating the nucleic acid molecule. Also provided is a method of inhibiting or destroying cells having a specific protease, such as cancer cells or inflammatory cells utilizing the nucleic acid molecules and proteins of the invention and pharmaceutical compositions for treating human inflammation and cancer.

Abstract: Novel methods are disclosed for forming a heterodimeric receptor complex with IL-28R and CRF2-4. The methods may be used for detecting and treating viral infections in in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: Novel conjugates of the pharmaceutically active metabolite of irinotecan and novel immunogens derived from this pharmaceutically active metabolite and monoclonal antibodies generated by these immunogens which are useful in immunoassays for the quantification and monitoring of the pharmaceutically active metabolite of irinotecan in biological fluids.

Abstract: This disclosure provides a multi-target fusion protein composed of a TNF-? antagonist domain and another binding domain antagonistic for a heterologous target, such as IL6, RANKL, IL7, IL17A/F, TWEAK, CSF2, IGF1, IGF2 or BLyS/APRIL, or agonistic for a heterologous target, such as IL10. The multi-specific fusion protein may also include an intervening domain that separates the binding domains and allows for dimerization. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

Abstract: The present invention provides isolated nucleic acid and amino acid sequences of sweet or amino acid taste receptors comprising T1R3 and T1R1, two heterologous G-protein coupled receptor polypeptides from the T1R family of sensory G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sweet and amino acid taste receptors.

Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: This invention relates to the delivery of agents to the body. One particular class of such agents are contrast agents useful in medical imaging techniques. The agents may be metals useful as contrast agents in magnetic resonance imaging (MRI), or in nuclear imaging, including positron emission tomography (PET), or as therapeutic agents in radiotherapy. The agents may alternatively be contrast agents useful in X-ray imaging. The invention also relates to methods by which agents for delivery to the body can be coupled to carriers and to targeting moieties effective to direct the agent to a specific locus within the body.

Abstract: The present invention provides technology for making large (e.g., greater than 50 amino acids), semi-synthetic, stapled or stitched proteins. The method essentially involves ligating a synthetically produced stapled or stitched peptide to a larger protein. Modified version of IL-13 and MYC are provided as illustrative examples.

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: The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc.

Abstract: The instant invention comprises a process of preparing a composition comprising directed sequence polymer (DSP) mixtures that act as epitopes and useful as vaccines, such DSP synthesized according to a set of rules regarding the identity and the frequency of occurrence of amino acids that substitute a base or native amino acid of a known epitope. The resulting composition is a mixture of related peptides for therapeutic use as a vaccine, preferably for infectious agents that are immune evasive.

Abstract: Targeted transcriptional effectors (transcription activators and transcription repressors) derived from meganucleases are described. Also described are nucleic acids encoding same, and methods of using same to regulate gene expression. The targeted transcriptional effectors can comprise (i) a meganuclease DNA-binding domain lacking endonuclease cleavage activity that binds to a target recognition site; and (ii) a transcription effector domain.

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 oxime, carbonyl, dicarbonyl, and/or hydroxylamine 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 oxime, carbonyl, dicarbonyl, and/or hydroxylamine 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: Disclosed herein are accelerants for the formation of oxime-containing compounds from the reaction of a carbonyl-containing compound and a hydroxylamine-containing compound. The oxime-containing compound, the carbonyl-containing compound and the hydroxylamine-containing compound can each be a non-natural amino acid or a non-natural amino acid polypeptide. Also disclosed is the use of such accelerants to form oxime-containing compounds, the resulting oxime-containing compounds, and reaction mixtures containing such accelerants.

Abstract: The present invention relates to a three-dimensional structure of the intracellular domain (AICD) of human amyloid precursor protein (APP695) in complex with human Fe65-PTB2 (i.e. a protein-complex comprising the intracellular domain (AICD) of human amyloid precursor protein (APP695) and the human Fe65-PTB2), as well as to methods and uses of said three-dimensional structure for identifying ligands which modify the interaction between the AICD and the Fe65-PTB2. Moreover, the present invention relates to pharmaceutical compositions which contain one or more of such identified ligands for the prevention or treatment of neurodegenerative disorders.

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: The invention relates to a long-acting formulation of biopharmaceutical, more specifically an aptamer therapeutics. A branched PEGylated aptamer or a hyaluronic acid (HA) derivative of which degradation in vivo is regulated is linked by the bioconjugation with biopharmaceutical to produce the long-action formulation.

Abstract: (+)-Avrainvillamide, a naturally occurring alkaloid with antiproliferative activity, is shown to bind to the oncoprotein nucleophosmin. Nucleophosmin is known to regulate the tumor suppressor protein p53 and is overexpressed in many different human tumors. The invention provides methods of modulating nucleophosmin and p53 using (+)-avrainvillamide and analogues thereof. These compounds may provide leads for the development of novel anti-cancer therapies that target nucleophosmin.

Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.

Abstract: The present invention provides a family of dark quenchers, termed Black Hole Quenchers (“BHQs”), that are efficient quenchers of excited state energy but which are themselves substantially non-fluorescent. Also provided are methods of using the BHQs, probes incorporating the BHQs and methods of using the probes.

Abstract: The present invention relates to a kit for the labelling of biomolecules bearing reactive amino or hydroxyl groups. The kit consists of a Reagent A and a Reagent B, individually packaged, comprising: a mixture of a carboxylated labelling compound and a tertiary amine (Reagent A); and a coupling reagent (Reagent B). Upon contacting Reagent A with Reagent B, the carboxylated labelling compound is activated in-situ by the coupling reagent (a guanidinium, or uranium salt) in the presence of the tertiary amine. The active form of the carboxylated labelling compound is reacted with a biomolecules bearing reactive amino or hydroxyl groups, with formation of a stable covalent bond between the carboxylated labelling compound and the biomolecule.

Abstract: Engineered proteins are used in the assembly of two-dimensional and three-dimensional nanostructure assemblies, based on systematic design and production of protein node structures that can be interconnected, for example, with streptavidin or streptavidin-incorporating struts to produce structures with defined dimensions and geometry. Nanostructure assemblies having utility as functional devices or as resists for the patterning of substrates have architectures including polygons, polyhedra, two-dimensional lattices, and three-dimensional lattices.

Abstract: Provided herein are peptide modulators of ion channels. Specifically, the peptide modulators comprise the amino acid sequence VEDEC wherein V is valine, E is glutamate, D is aspartate, C is cysteine. In certain embodiments, the modulator is attached to the C-terminal end of Slo1 protein isoform. The present invention also claims conjugations of the first valine that make the peptide modulator more membrane permeable, such as myristoyl moieties and arginine-rich cell penetrating peptides. The present invention contemplates use of the peptide modulators in the treatment of diseases/malfunctions such as epilepsy, chronic pain, migraine, asthma, chronic obstructive pulmonary disease, urinary incontinence, hypertension, erectile dysfunction, irritable bowel syndrome, renal disorders of electrolyte imbalance, and possibly in certain kinds of cancer.

Abstract: The invention relates to chemiluminescent compounds of general formula (I) wherein: either: R1 is a reactive group capable of reacting with an amine or thiol moiety; L1 is a hydrocarbon linker moiety comprising 2-12 carbon atoms, optionally substituted with hydroxy, halo, nitro or C1-C4 alkoxy; and R2 is hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, aryl, fused aryl, C1-C4 alkoxy, C1-C4 acyl, halide, hydroxy or nitro; or, alternatively: the combination R1-L1- comprises a C1-C4 alkyl group optionally substituted with hydroxy, halo, nitro or C1-C4 alkoxy; and R2 comprises a group R4-L1-, where R4 is a reactive group capable of reacting with an amine or thiol moiety; and L1 is as defined above; L2 is —C(?O)O—, —C(?O)—S— or —C(?O)N(SO2R5)—, wherein, in each case, the —C(?O) is linked to the ring carbon atom, and R5 is C1-C8 alkyl, aryl, C1-C8 alkoxy or C1-C8 acyl; R3 is a substituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or aryl group wherein at least one of the said substituents is electron-withdrawi

Abstract: The present invention provides a method for producing a protein which has a restored native higher-order structure by bringing a protein which has lost its native higher-order structure into contact at pH 6.5 to 9.0 with a 1 to 3% aqueous solution of a specific surfactant, such as lauroylglutamic acid to obtain a solubilized solution of the protein; and then adding the solubilized solution to a buffer with pH 6.5 to 9.0 containing arginine or an arginine derivative at a concentration of 0.1 to 1.2 M to lower the concentration of the specific surfactant, such as lauroylglutamic acid, in the obtained mixture solution down to 0.02 to 0.275%. According to the present invention, it is possible to easily restore the native higher-order structure of a protein while smoothly removing the surfactant from the protein.

Abstract: The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds having the general formula U1-M-U2 wherein M is a linking group covalently joining R2, R3, R4 or R5 of U1 to an R2, R3, R4 or R5 group of U2; U1 and U2 have the general formula (I) and G, X1, X2, R2, R3, R3?, R4, R4? and R5, are as described herein.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

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

Abstract: Activated haptens useful for generating immunogens to HIV protease inhibitors, immunogens useful for producing antibodies to HIV protease inhibitors, and antibodies and labeled conjugates useful in immunoassays for the HIV protease inhibitor saquinavir. The novel haptens feature an activated functionality at the central, non-terminal hydroxyl group. Also described are monoclonal antibodies specific for saquinavir having less than 10% cross-reactivity with lopinavir, nelfinavir, amprenavir, ritonavir, and indinavir, and a murine hybridoma producing said antibodies.

Abstract: The present invention describes methods for the production and use of single chain (single-stranded) fluorescence resonance energy transfer (“FRET”) DNA or RNA aptamers containing fluorophores (F) and quenchers (Q) at various loci within their structures, such that when its specific matching analyte is bound and the FRET-aptamers are excited by specific wavelengths of light, the fluorescence intensity of the system is modulated (increased or decreased) in proportion to the amount of analyte added. F and Q are covalently linked to nucleotide triphosphates (NTPs), which are incorporated by various nucleic acid polymerases such as Taq polymerase during the polymerase chain reaction (PCR) and then selected by affinity chromatographic, size-exclusion or molecular sieving, and fluorescence techniques. Further separation of related FRET-aptamers can be achieved by ion-pair reverse phase high performance liquid chromatography (HPLC) or other types of chromatography.

Abstract: Compounds of formula (I): wherein X is selected from CRX and N; RN1 is selected from H and C1-4 alkyl, which may be substituted by SH or halo; RG1 is selected from H and SH; RC2 is selected from H and optionally substituted C1-7 alkyl; RC3 is selected from H and optionally substituted C1-7 alkyl; Rx is selected from H, OH and NH2; RC4 is selected from: (i) an optionally substituted C3-12 N-containing heterocyclyl; (ii) C(?O)NRN5RN6, where RN5 and RN6 are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl or RN5 and RN6 and the nitrogen atom to which they are attached form an optionally substituted N-containing C5-7 heterocyclyl group; (iii) C(?O)ORO1, where RO1 is selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl; (iv) C(?O)NHNHSO2RS1, where RS1 is selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heteroc

Abstract: A new method is disclosed for the exfoliation of hexagonal boron nitride into mono- and few-layered nanosheets (or nanoplatelets, nanomesh, nanoribbons). The method does not necessarily require high temperature or vacuum, but uses commercially available h-BN powders (or those derived from these materials, bulk crystals) and only requires wet chemical processing. The method is facile, cost efficient, and scalable. The resultant exfoliated h-BN is dispersible in an organic solvent or water thus amenable for solution processing for unique microelectronic or composite applications.

Abstract: The presently disclosed subject matter provides dyes having an improved photostability, biosensors comprising such dyes, and methods of use thereof, including methods for detecting target molecules in a sample under test and for live-cell imaging. The dyes can include a binding member, including a biomolecule or fragments thereof, which can interact with target molecules of interest and can be specific to a given conformational state or covalent modification, e.g., phosphorylation, of the target molecule. The presently disclosed dyes can be used for detecting changes in the binding, conformational change, or posttranslational modification of the target molecule.

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 object of the present invention is to provide a translationally regulatable mRNA which has wider application and can perform specific ON-OFF regulation, an RNA-protein complex specifically bound to the mRNA, and a translational regulatory system. The present invention provides an mRNA having an RNA-protein complex interacting motif-derived nucleotide sequence 5? to the ribosome-binding site or within the 5? region of the open reading frame, and an mRNA having a nucleotide sequence complementary to an RNA-protein complex interacting motif-derived nucleotide sequence 5? to the ribosome-binding site or within the 5? region of the open reading frame.

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 present invention relates to the use of quantitative assay, in particular in vitro, in a biological sample, of the degree of nitration of tyrosine residues of a particular nitrated protein or physiological peptide sequence, for the implementation of a method of in vitro diagnosis of the state of severity and progressiveness of a chronic or acute pathology associated with nitrating stress.

Abstract: Described are cotton fibres, yarns and fabrics functionalized with aminoglycoside antibiotics and a gelatin, for the production of bandaging for skin wounds and lesions which, by allowing a lengthy period of protection from infection risk, require less frequent changing than traditional bandages, and enable a better and faster healing of the wounds or lesions.

Abstract: The invention provides a method of modifying a phosphomonoester moiety of a target compound. The method can include the steps of (a) providing a target compound having an electrophilic moiety and a phosphomonoester moiety; (b) contacting the target compound with a first carbodiimide compound under conditions for preferential addition of the first carbodiimide compound to the electrophilic moiety over the phosphomonoester moiety, thereby forming an electrophile-protected target compound; and (c) contacting the electrophile-protected target compound with a second carbodiimide compound and a nucleophilic compound under conditions for addition of the nucleophilic compound to the phosphomonoester.

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 invention generally features the use of Yaba monkey tumor virus nucleic acid molecules and polypeptides for the treatment or prevention of immunoinflammatory disorders.

Abstract: The present invention relates to highly conjugated proteins and methods for making such proteins. In particular, the present invention relates to methods for linking additional sites to a protein for conjugation with activated polyethylene glycol (PEG) linkers, without denaturing the protein. The invention also relates to highly conjugated proteins with decreased immunogenicity and increased circulating half-life.