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: The invention provides methods and compositions useful for identifying polypeptides with desired characteristics in vitro.

Abstract: The invention provides optical agents, including compositions, preparations and formulations, and methods of using and making optical agents. Optical agents of the present invention include dyes, and derivatives thereof, having a fused ring backbone structure having dithienofuran core. In some embodiments, dyes of the present invention are dithienofuran dyes having a dithienofuran core optionally functionalized to provide useful optical, biological, pharmacokinetic and/or physical properties.

Abstract: The invention provides optical agents, including compositions, preparations and formulations, and methods of using and making optical agents. Optical agents of the present invention include dyes, and derivatives thereof, having a fused ring backbone structure having dithienopyrrole core. In some embodiments, dyes of the present invention are dithienopyrrole dyes having a dithienopyrrole core optionally functionalized to provide useful optical, biological, pharmacokinetic and/or physical properties.

Abstract: The present invention is directed to probes and methods for the imaging of specimens such as tissue samples or other biological specimens or arrays using mass spectrometry (MS). In one aspect, there is provided a method for analysing a specimen comprising the steps of contacting the specimen with probe molecules each of which includes one or more mass tags coupled to each probe molecule via a first cleavable linker, contacting the specimen with a Matrix-assisted Laser Desorption lonisation (MALDI) matrix or similar material, irradiating a portion of the specimen with a laser beam to release ions from the specimen, selecting released ions with mass-to-charge ratios corresponding to the mass tags or derivatives of the mass tags, and recording the amount and type of ions selected together with the location of the portion of the specimen. The irradiation, selection and recording steps are then repeated on a different portion of the specimen.

Abstract: Provided are methods and devices for single-molecule genomic analysis. In one embodiment, the methods entail processing a double-stranded nucleic acid and characterizing said nucleic acid. These methods are useful in, e.g., determining structural variations and copy number variations between individuals.

Abstract: The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

Abstract: Provided herein are water-soluble carbohydrate polymers which are monoderivatized at their reducing terminus, such that the carbohydrate polymers can be selectively conjugated at a single location. Also provided are methods of preparation and conjugation of the monoderivatized carbohydrate polymers.

Abstract: Provided herein are conjugates including a targeting vehicle coupled to an agent. The targeting vehicle includes a tachykinin receptor ligand and a reactive moiety. Conjugates including a tachykinin receptor ligand attached to an antibody or fragment thereof that is specific for an intracellular target are also provided. Also provided are methods of delivering agents to cells expressing tachykinin receptors, methods of delivering antibodies or fragments thereof to an intracellular extra-endosomal target, and methods of arresting cell growth or introducing cell death of a cancer cell.

Abstract: A method and compound for treating skeletal muscle mass deficiency in a human subject are disclosed. The composition is an oligomer of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5? exocyclic carbon of an adjacent subunit, contains between 10-40 nucleotide bases, has a base sequence effective to hybridize to an expression-sensitive region of processed or preprocessed human myostatin RNA transcript, identified, in its processed form, by SEQ ID NO:6, and is capable of uptake by target muscle cells in the subject. In practicing the method, the compound is administered in an amount and at a dosage schedule to produce an overall reduction in the level of serum myostatin measured in the patient, and preferably to bring the myostatin level within the a range determined for normal, healthy individuals.

Abstract: Embodiments of the present disclosure relate generally to reporter compositions which are synthetic nucleotides that comprise nucleotides with a high charge mass moiety attached thereto via a linker molecule. The linker molecules can vary in length in part to enable the high charge mass moiety to extend out from a DNA polymerase complex so that polymerization may not be influenced.

Abstract: The present invention provides an immunogenic composition comprising at least one antigen delivery particle and at least one antigen, wherein the antigen and antigen delivery particle are linked using an intermediate linker.

Abstract: The isolation and identification of glycosaminoglycans capable of binding to proteins having a heparin-binding domain is disclosed, as well as the use of the glycosaminoglycans isolated in the growth and/or development of tissue.

Abstract: The present invention features compositions and methods that make use of complexes comprising one or more inhibitory nucleic acids and a targeting polypeptide, wherein the targeting polypeptide consists of a cell surface receptor ligand. The compositions can be used in methods of silencing gene expression in a cell, in delivering agents to a target cell, and in treating or preventing a disease or disorder in a subject.

Abstract: In general, the invention relates to novel bioactive pentapeptides from heat stabilized defatted rice bran having anti-cancer, anti-obesity, anti-Alzheimer and other health-promoting activities proteins. The bioactive pentapeptides can be incorporated into pharmaceutical, nutraceuticals and food compositions having at least the bioactive pentapeptide as an active ingredient.

Abstract: The invention concerns a method for determining at least one target molecule map in a tissue section, using at east one (A-X)n-B conjugate, wherein A is a tag molecule of known molecular weight, X is a linker that is cleaved during sample desorption/ionization, n is an integer of at least 1, and B is a binding molecule that binds specifically to said target molecule. When using MALDI mass spectrometry, said linker molecule X may be cleaved by photodissociation during sample laser irradiation if photocleavable at the wavelength of said MALDI laser. Alternatively, when using UV-MALDI, IR-MALDI, SIMS or DESI mass spectrometry, said linker molecule X may be cleaved by fragmentation during sample desorption/ionization.

Abstract: One aspect of the invention relates to a peptide comprising the amino acid sequence of formula (I), ENPVVHFFK91NIVTP96RTP?(I)? (SEQ?ID?NO:?3) wherein at least one of K91 and P96 is substituted by a natural or unnatural amino acid, wherein said peptide is in linear or cyclic form. Another aspect of the invention relates to a peptide comprising the amino acid sequence of formula (Ia), ENPVVHFFK91NIVT96RTP?(Ia), (SEQ?ID?NO:?4) wherein each of K91 and P96 is substituted by a natural or unnatural amino acid. Another aspect of the invention relates to a peptide comprising the amino acid sequence of formula (Ib), ENPVVHFFK91NIVT96RTP?(Ib) (SEQ?ID?NO:?5) wherein at least one of K91 and P96 is substituted by an amino acid selected from R, E, F and Y.

Abstract: The present invention provides polymers, compositions thereof, and polyplexes comprising said polymers. In particular, cationic polymers, pegylated versions thereof, and polynucleotide containing polyplexes comprising such polymers are provided. The invention further provides methods of using said polymers and polyplexes.

Abstract: The present invention provides building blocks and methods for synthesizing very pure RNA in a form that can efficiently be modified at the 3? end. Reverse RNA monomer phosphoramidites have been developed for RNA synthesis in 5??3? direction, leading to very clean oligo synthesis that allows for the introduction of various modifications at the 3?-end cleanly and efficiently. Higher coupling efficiency per step have been observed during automated oligo synthesis with the reverse RNA amidites disclosed herein, resulting in a greater ability to achieve higher purity and produce very long oligonucleotides. The use of the reverse RNA phosphoramidites in the synthetic process of this invention leads to oligonucleotides free of N+1 species.

Abstract: This invention relates to a non-coding RNA (ncRNA) sequence from Human cytomegalovirus (HCMV) (termed “TRL4”) that specifically protects neuronal cells from cell death and may therefore be useful in the treatment of neurodegenerative disorders, such as Parkinson's disease.

Abstract: The invention relates to hyperglycosylated human coagulation factor IX polypeptides, to processes for preparing said polypeptides, to pharmaceutical compositions comprising said polypeptides and to the use of the compounds for the treatment of diseases alleviated by human coagulation factor IX, in particular, but not exclusively hemophilia.

Abstract: Isolated glycan binding peptide complex comprise two or more glycan binding peptides operatively coupled to each other. These are bacterial binding peptide conjugates (e.g., glycan binding peptides) to a multivalent polymer (e.g., a multivalent PEG molecule) or to the surface of particles that create multimeric constructs that inhibit growth and aggregation of microbes. Included is a method of evaluating a substance for the presence of a microbe comprising contacting the substance with a peptide microarray or a peptide complex comprising a plurality glycan binding peptide operatively coupled to a substrate or multivalent linker, wherein the glycan binding peptide is coupled to an array by a linker that is at least 0.5 micrometers in length.

Abstract: A construct comprising a cell delivery peptide covalently attached to a biologically active compound suitable for delivery of said biologically active compound into cells, wherein optionally the cells are cardiac muscle, skeletal muscle, smooth muscle or contractile cells.

Abstract: The present invention provides an isolated peptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:36, as well as derivatives thereof comprising various N-terminal and C-terminal chemical moieties, substituted analogs thereof, and fragments thereof. The peptides of the invention are useful for treating and preventing a Flavivirus invention. Pharmaceutical compositions comprising the peptides, and methods of treating or preventing Flavivirus infections, are also provided.

Abstract: The present invention provides fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV. The fusion peptide comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) C-terminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. Component (II) is preferably a full or partial version of IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2/GLP-1(7-35, 36 or 37) or GLP-2. The fusion peptide may be produced in engineered cells or synthetically and may be used for the preparation of a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.

Abstract: Embodiments of the present invention provide methods and nucleic acid reporter molecules for the detection of nucleic acid in a sample. The nucleic acid reporter molecule comprises two unsymmetrical cyanine monomer moieties, which may be the same or different, that are covalently attached by a linker comprising at least one aromatic, heteroaromatic, cyclic or heterocyclic moiety comprising 3-20 non-hydrogen atoms selected from the group consisting of O, N, S, P and C. The linker may be rigid, relatively flexible or some degree thereof. The unsymmetrical cyanine monomer moieties comprise a substituted or unsubstituted benzazolium moiety and a substituted or unsubstituted pyridinium or quinolinium moiety that is connected by a methine bridge that is monomethine, trimethine or pentamethine. The linkers form the cyanine dimer compounds by attaching to the pyridinium or quinolinium moiety of the monomer moieties.

Abstract: A therapeutic agent formed of a magnetic resonance imaging tracer conjugated with a chemotherapeutic agent. The therapeutic agents can be used in measuring drug delivery to a target tissue. The therapeutic agents allow for therapeutic MRI, in which 19F MRI techniques are used to detect, monitor, evaluate, and/or adjust chemotherapeutic drug dosage levels in a patient or a targeted tissue thereof.

Abstract: Compounds comprising a diagnostic or therapeutic moiety can be retained inside a cell by conjugating the moiety to at least one PNA that is targeted to the transcripts from a gene of interest. The diagnostic or therapeutic moiety is also conjugated to at least one targeting moiety specific for an extracellular receptor or other cell surface molecule. The targeting moiety binds to the surface of a cell, and the entire compound is then internalized. Once inside the cell, the PNA portion of the diagnostic or therapeutic compound binds to RNA transcripts in a sequence specific manner. Binding of the PNA to its target RNA transcript retains the compound within the cell. The PNA can be designed to bind to a predetermined nucleic acid sequence from an RNA transcript, for example a mutated or overexpressed sequence that is characteristic of a pathological state.

Abstract: Cyanine-type fluorescent dyes modified with an alkynyl linker arm of formula (I), suitable for the conjugation of biomolecules, such as for example nucleosides, nucleotides, oligonucleotides, nucleic acids, proteins, peptides, vitamins and hormones. A method and intermediates for the synthesis of the alkynyl cyanines of the invention are also described, as well as alkynyl cyanine-biomolecule conjugates and methods for preparing thereof. The alkynyl cyanines can be advantageously used as markers for biomolecules or as quenchers.

Abstract: Compositions and methods for tissue repair are provided including cell binding peptides and growth factor binding peptides. The cell binding peptides bind to one or more of stem cells, fibroblasts, or endothelial cells. The growth factor binding peptides include platelet derived growth factor (PDGF) binding peptides and growth differentiation factor (GDF) binding peptides. The tissue for repair includes tendon, muscle, connective tissue, ligament, cardiac tissue, vascular tissue, or dermis. Implantable devices for tissue repair are provided to which the cell and growth factor binding peptides are attached, such as acellular extracellular matrix having attached binding peptide.

Abstract: Compositions and methods for tissue repair are provided including cell binding peptides and growth factor binding peptides. The cell binding peptides bind to one or more of stem cells, fibroblasts, or endothelial cells. The growth factor binding peptides include platelet derived growth factor (PDGF) binding peptides and growth differentiation factor (GDF) binding peptides. The tissue for repair includes tendon, muscle, connective tissue, ligament, cardiac tissue, vascular tissue, or dermis. Implantable devices for tissue repair are provided to which the cell and growth factor binding peptides are attached, such as acellular extracellular matrix having attached binding peptide.

Abstract: Novel classes of multi-arm polyalkylene oxide-based materials including PEG nanocarriers, nanogel particles, and aggregated nanogel particles are disclosed. These classes of compositions may be associated with therapeutic agents and targeting moieties, or visibility enhancing agents, and may have a modified surface structure. In some embodiments the PEG-based materials can be made to provide relatively high drug loads with improved solubility and targeted delivery.

Abstract: The present invention can provide a novel saccharide primer, which makes it possible to efficiently synthesize a sugar chain, and a method for using the primer. According to the present invention, the saccharide primer of the present invention is a saccharide primer having an alkenyl chain that has one or more double bonds in a position other than the alkyl chain terminal, and represented by the following general formula (I): Lac-O-Ck:m(n) ??General formula (I) In the general formula (I), Ck represents an alkenyl chain, m represents a total number of double bonds, and n represents a position of the double bond in the alkenyl chain. Here, k is preferably an integer in the range of 8 to 14, and particularly 12 or 13. In addition, when m is 1, n is an integer satisfying 1?n?k?2; and when m satisfies 2?m?k?1, n is a plurality of integers satisfying 1?n?k?1.

Abstract: Disclosed are peptide nucleic acid (PNA) probes, a kit and a method for expression profiling of microRNAs (miRNAs), which play an important role in regulation of expression of genes encoding proteins.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing a target RNA and protein levels via use of Dicer substrate siRNA (DsiRNA)-peptide conjugates.

Abstract: The invention relates to glycoside-compound conjugates for use in antisense strategies and/or gene therapy. The conjugates comprise a glycoside linked to a compound, in which the glycoside is a ligand capable of binding to a mannose-6-phosphate receptor of a muscle cell. For example the cells are muscle cells of a Duchenne Muscular Dystrophy (DMD) patient and the conjugate comprises an antisense oligonucleotide which causes exon skipping and induces or restores the synthesis of dystrophin or variants thereof.

Abstract: The present invention relates to an immunoglobulin-binding protein, wherein at least one asparagine residue has been mutated to an amino acid other than glutamine or aspartic acid, which mutation confers an increased chemical stability at pH-values of up to about 13-14 compared to the parental molecule. The protein can for example be derived from a protein capable of binding to other regions of the immunoglobulin molecule than the complementarity determining regions (CDR), such as protein A, and preferably the B-domain of Staphylococcal protein A. The invention also relates to a matrix for affinity separation, which comprises an immunoglobulin-binding protein as ligand coupled to a solid support, in which protein ligand at least one asparagine residue has been mutated to an amino acid other than glutamine.

Abstract: This invention relates to a conjugated molecule comprising a peptide derived from the CD4 receptor coupled to an organic molecule by means of a linker as well as a process for its preparation. Such a conjugated molecule can be used in antiviral treatment, namely in the treatment of AIDS.

Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidized polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.

Abstract: The present invention discloses cell penetrating peptides and conjugates of a cell penetrating peptide and a cargo molecule.

Abstract: A test indicator for quantifying remaining liver function is provided. A novel liver receptor imaging agent with liver targeting property is utilized to develop a method for quantifying remaining liver function to serve as test indicator for judging the liver failure outcome in clinic, particularly for judging the necessity of liver transplantation for patients with liver failure or liver disease. The radioactivity uptake of the test indicator was negatively correlated with the extent of liver reserve. The cutoff value of liver reserve for liver transplantation is also disclosed.

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: A radiolabeling method using a multivalent glycoligand as hepatic receptor imaging agent is provided. The multivalent glycoligand-DTPA derivatives (In-111-DTPA-hexa lactoside and In-111-DTPA-tri-galactosamine glycoside) labeled with In-111 are used as hepatic receptor imaging agent. The effects of imaging of a hepatic receptor in different species are evaluated, the lowest specific radioactivity values of hepatic receptor imaging required in different species are discovered. Since the specificity of the human ASGPR closely resembles that of the mouse. This kind of radiolabelling method, agent and related study about specific radioactivity could be used in clinical trial in the future.

Abstract: Compositions containing a therapeutic peptide covalently linked to Vitamin B12 at the 5?-hydroxyl group of the ribose moiety of ?-ligand are described. The length of the linkage is optimized so that the biological activity of both the Vitamin B12 and the therapeutic peptide is maintained. Therapeutic peptides for conjugation with vitamin B12 include insulin, PYY, NPY and GLP-1. Attachment to Vitamin B12 provides uptake of the therapeutic peptide from the digestive tract and longer residence time.

Abstract: The present invention relates to the use of a toxin moiety (e.g., a chlorotoxin moiety) as a carrier for therapeutic agents, e.g., therapeutic agents that require intracellular uptake to exert their effects. For example, in some embodiments, the present invention provides conjugates comprising a toxin (e.g., a chlorotoxin) moiety and an anti-cancer moiety and methods for using such conjugates to increase cellular uptake and/or increase specificity for cancer cells of the anti-cancer drug. In some embodiments, the present invention provides conjugates comprising a toxin moiety (e.g., a chlorotoxin moiety) and a nucleic acid agent. Also provided are methods of treatment involving administration of such conjugates, and pharmaceutical compositions and kits useful for carrying out such methods of treatment.

Abstract: This invention relates to compositions and methods for the use of anti-autoimmune reagents that specifically bind to anti-desmoglein antibodies, which are responsible for pemphigus foliaceus. In addition, the invention relates to methods and compositions for inhibiting the expression or function of a variable region of an anti-desmoglein (anti-Dsg) pathogenic autoantibody.

Abstract: This document provides methods and materials related to composites or coatings containing polypeptides attached to polysaccharides and/or molecules. For example, methods and materials related to composites or coatings containing polypeptides (e.g., casein polypeptides) attached to polysaccharides (e.g., cellulose) and/or molecules (e.g., calcium containing molecules such as calcium phosphate and calcium carbonate and/or polyesters such as polylactic acid and polyhydroxybutyrate) are provided. A coating provided herein can include both cationic and ionic polymers, polypeptides, or polysaccharides.

Abstract: The invention include glycopeptides having a glycoside and a peptide covalently bound through an amide bond. The glycopeptides may also include a diagnostic or therapeutic agent bound to the glycopeptide. A metal, such as a radionuclide, may also be chelated to the glycopeptide. Specific embodiments of the invention relate to glycopeptides made of chitosan covalently bound to a poly(amino acid) such as poly(glutamic acid) or poly(aspartic acid). Diagnostic agents conjugated to the glycopeptide may facilitate imaging. Specific therapeutic agents that may be conjugated to the glycopeptide include anticancer drugs, rheumatoid arthritis drugs, anticoagulants, anti-angiogenesis drugs, apoptosis drugs, osteoporosis drugs, steroids, and anti-inflammatory drugs. Some agents, such as radionuclides, may have both diagnostic and therapeutic effects.

Abstract: The present invention provides siRNA delivery methods use in vivo or in vitro. The delivery methods include conjugation with delivery peptides and mixing with dendrimers.

Abstract: The invention provides a delivery system comprising a cell penetrating peptide, a polyarginine peptide, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.