Abstract: The present invention relates to fluorescent dyes in general. The present invention provides a wide range of fluorescent dyes and kits containing the same, which are applicable for labeling a variety of biomolecules, cells and microorganisms. The present invention also provides various methods of using the fluorescent dyes for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions.

Abstract: A compound of the general formula X-[Q-W—(CH?CH)n—(CH2)2-L]m (I) in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing group; n represents 0 or an integer of from 1 to 4; L represents a leaving group; and m represent an integer of from 1 to 8. The compounds find use in the conjugation of biological molecules.

Abstract: There is provided a method of conjugating a polymer containing a free aldehyde group with a flavonoid in the presence of an acid catalyst, such that the polymer is conjugated to the C6 or C8 position of the flavonoid A ring. The resulting conjugates may be used to form delivery vehicles to deliver high doses of flavonoids, and may also be used as delivery vehicles to deliver an additional bioactive agent.

Abstract: The present invention relates to a method of preparing modified polypeptides, by linking a target polypeptide to a carrier molecule that is designed to bear one or more water-soluble polymer molecules, via protein trans-splicing. The polymer molecules can be attached to the carrier molecule either before or after ligation to the target polypeptide. Novel protein trans-splicing elements (known as “split inteins”) and trans-splicing partners are also provided.

Abstract: A method of one reaction step for synthesis of peptide template fluorescent metal nanoclusters as bioprobes. Specific targeting peptide containing a metal reactive group is synthesized and used to react with a metal salt solution under a sufficient pH condition at room temperature in forming peptide template fluorescent metal nanoclusters. The dialyzed metal nanoclusters is used directly as bio-probes.

Abstract: The present application discloses compositions and methods of synthesis and use of 68Ga, 18F or 19F labeled molecules of use in PET or MRI imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a chelating moiety, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 68Ga, 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. In more preferred embodiments, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment.

Abstract: Novel biologically active compounds of the general formula (I) in which one of X and X? represents a polymer, and the other represents a hydrogen atom; each Q independently represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; or, if X? represents a polymer, X-Q-W— together may represent an electron withdrawing group; and in addition, if X represents a polymer, X? and electron withdrawing group W together with the interjacent atoms may form a ring; each of Z1 and Z2 independently represents a group derived from a biological molecule, each of which is linked to A and B via a nucleophilic moiety; or Z1 and Z2 together represent a single group derived from a biological molecule which is linked to A and B via two nucleophilic moieties; A is a C1-5 alkylene or alkenylene chain; and B is a bond or a C1-4 alkylene or alkenylene chain; are formed by conjugating a suitable polymer to a suitable biologically active molecule via nuc

Abstract: The invention provides compounds of the formula Poly-([SP-LI]n-PL-L2) including a collection of 152 peptides useful to create the compounds, and their uses thereof for the treatment of a variety of mammalian diseases. The compound, a novel ligand-targeted multi-stereoisomer peptide polymer conjugate, comprises two or more stereoisomer peptides and a peptide-ligand conjugated via linkers to a biocompatible hydrophilic polymer, preferably HPMA. The increased stability and solubility of the compound carrying the stereoisomer peptides and a peptide-ligand provide ideal pharmaceutical properties including the delivery by the polymer of the peptides into the target cells. The compounds of the invention are useful therapeutics for the treatment of a variety of mammalian diseases.

Abstract: Process for the separation of a biomolecule containing at least one cationic group from a liquid medium containing said biomolecule, which comprises the use of a tetraphenylborate (TPB) salt.

Abstract: Polypeptides labelled with a donor and acceptor pair of dyes selected from a dibenzorhodamine dye and a diamino-benzophenoxazine dye are peptide conjugates which are useful for intracellular and bead-based assays with fluorescence detection. Peptide conjugates with a caspase-recognition site undergo cleavage into peptide fragments which may be detected, located, and quantitated by the changes in fluorescence. Intracellular cleavage of peptide conjugates is correlated with apoptosis.

Abstract: A method for covalent attachment of peptides to luminescent quantum dots or other inorganic nanoparticles. The first step in the method involves functionalizing at least a portion of a surface of the quantum dot or nanoparticle with one or more materials having at least one reactive functional group therein. Subsequently, a peptide having a reactive functional group is reacted with at least some of the quantum dot or nanoparticle reactive functional groups to covalently bond at least some of the peptide to the quantum dots or nanoparticles. Modifications of the basic method are disclosed which provide methods allowing customized fabrication of quantum dots having a variety of different functional properties and combinations of functional properties. Also disclosed are quantum dots and nanoparticles made by the methods of the present invention.

Abstract: The invention relates to a modifying agent comprising a water soluble polymer, wherein the water soluble polymer comprises at least one reactive selenium group, said reactive selenium group being capable of reacting with a thiol group thereby forming an —Se—S— bond. Furthermore, the invention relates to a method for producing said modifying agents and their use in the modification of pharmaceutically active agents, e.g. G-CSF. Additionally, the invention concerns conjugates comprising a water-soluble polymer and a pharmaceutically active agent, wherein the water-soluble polymer is linked via a S—Se-bond to agent and a method for their production and their use as medicaments. Finally, the invention concerns a pharmaceutical composition comprising the inventive conjugates.

Abstract: The present invention relates to new arginine substituted peptides designed based on the sequence of human lactoferrin and to use thereof, in particular for treatment and/or prevention of infections, inflammations, tumours, pain, wounds and/or scars.

Abstract: Described herein are crosslinked compounds useful in numerous treatments. Described herein are methods of making crosslinked compounds via (1) die oxidative coupling of two or more thiol compounds or (2) by the reaction between at least one thiol compound with at least one thiol-reactive compound.

Abstract: Compositions and methods for controlling or eliminating isotope effects during fractionation of chemically equivalent but isotopically distinct compounds. Isotope coding agents contain heavy isotopes other than deuterium. The invention facilitates intelligent data acquisition. After sample fractionation, isotope abundance ratios are calculated using mass spectrometry, and analytes of interest are identified in real time.

Abstract: Methods for introducing fluorine atom onto a polypeptide are provided. Also provided are linkers, bioconjugates, and bifunctional compound agents made using the methods, linkers, and bioconjugates. The methods comprise: (i) providing a linker comprising a thiol-reactive terminus and an aldehyde-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a polypeptide comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the aldehyde-reactive terminus of the linker with a fluorine-substituted aldehyde.

Abstract: The invention provides methods and systems of determining biopolymer profiles and correlations between structural units (residues) of a biopolymer based on sampling of the conformational space available to the molecule. The correlations between these structural units can further be used to find networks within a biopolymer such as the coupled residue networks in a protein. The invention also provides for designing and engineering biopolymers including polypeptides, nucleic acids and carbohydrates using the information derived from the conformation clustering and subsequent methods described herein.

Abstract: The present invention is to provide a method for easily and specifically modifying specific amino acid residue(s) constituting a peptide and to provide a methodology of improving the accuracy of identification of the peptide using a new information of the peptide obtained from the number of modified amino acid residue by said specific modification method as mentioned. The method for modifying a peptide according to the present invention is characterized: A method for modifying a peptide, wherein the peptide as supported in a substrate and an aqueous solution of perhalogenated carboxylic acid containing an alcohol is reacted to selectively esterify a glutamic acid residue of said peptide.

Abstract: The invention relates to the use of oligomers and polymers capable of rendering insoluble drugs soluble, protecting unstable drugs, and facilitating the delivery of drugs to their site of action. This invention further relates to processes for the preparation of such oligomers and polymers, and to compositions containing them. In some instances, oligomers, polymers, and/or mixtures thereof can be used to protect a protein drug. Such structures can include at least one recognition element covalently attached to a hydrophilic element, wherein said recognition element or elements interact noncovalently with the protein drug to form a complex in which said protein drug is protected from degradation, recognition by the immune system, and/or renal excretion.

Abstract: The present invention relates to a multi-conjugate of small interfering RNA (siRNA) and a preparing method of the same, more precisely a multi-conjugate of siRNA prepared by direct binding of double stranded sense/antisense siRNA monomers or indirect covalent bonding mediated by a cross-linking agent or a polymer, and a preparing method of the same. The preparing method of a siRNA multi-conjugate of the present invention is characterized by simple and efficient reaction and thereby the prepared siRNA multi-conjugate of the present invention has high molecular weight multiple times the conventional siRNA, so that it has high negative charge density, suggesting that it has excellent ionic interaction with a cationic gene carrier and high gene delivery efficiency.

Abstract: Disclosed is a peptide immobilization technique which can achieve the immobilization of a satisfactory quantity of a peptide on a solid support. In the immobilization of a peptide on a solid support, a surfactant is allowed to coexist on the solid support together with the peptide. In this manner, the quantity of the peptide immobilized on the solid support can be increased.

Abstract: A method of making a fluorogenic peptide with an acridone fluorophor is provided, the method comprising the steps of: (a) providing an acridone derivative, said acridone derivative having first and second reactive groups (or precursors thereof), (b) providing a solid phase support provided with reactive species for reacting with the first reactive group of the acridone derivative (c) causing the solid phase support and acridone derivative to react so that the acridone derivative is attached to the solid phase support (d) providing the peptide or reagents for the formation of the peptide, and (e) subsequent to step (c), causing the reaction of the second acridone reactive group with the peptide or one or more of the reagents for the formation of the peptide.

Abstract: The invention relates to method of detecting autoantibodies from patients suffering from rheumatoid arthritis. To this end, according to the invention, at least two peptide units are used of which at least one peptide unit comprises a part not derived from (pro)filaggrin, fibrin, fibrinogen, vimentin, cytokeratin 1 and cytokeratin 9, and which peptide unit comprises the motif XG, and a peptide unit comprising the motif XnonG, wherein X is a citrulline or an analogue thereof, and nonG is an amino acid other than glycine.

Abstract: The present invention provides a method for analyzing the C-terminal amino acid sequence of a peptide by using a reaction for successively releasing the C-terminal amino acids of the peptide, which method can suppress, when successively releasing the C-terminal amino acids of a peptide of long amino acid length, such a undesirable side reaction as cleavage of peptide bond in the intermediate position of the peptide and can carry out the chemical treatment thereof under widely applicable conditions; In the method, a dry sample of a peptide with long amino acid length is beforehand subjected to an N-acylation treatment; by using a reaction reagent where an alkanoic acid anhydride is combined with a small amount of a perfluoroalkanoic acid, successive release of C-terminal amino acids is conducted under mild conditions; a hydrolysis treatment is applied; then, selective fragmentization at site of arginine residue is performed by digestion by trypsin; thereafter, decreases in molecular weight are measured for the

Abstract: The invention provides a complex including a cation and an insulin compound conjugate. The insulin compound conjugate includes insulin compound, such as human insulin or an analog thereof, conjugated to a modifying moiety, such as a polyethylene glycol moiety. The invention also includes solids and pharmaceutical compositions including such complexes, methods of making such complexes, and methods of using such complexes in the treatment of insulin compound deficiencies and other ailments. Further, the invention includes novel insulin compound conjugates and modifying moieties for use in making novel insulin compound conjugates. The invention also includes fatty acid compositions for administration of pharmaceutical agents, such as the novel insulin compound conjugates, and/or the cation-insulin compound conjugate complexes of the invention.

Abstract: The present invention relates to an activated peptide derived from the CD4 receptor, which is capable of coupling by covalent bonding to an organic molecule and thus makes it possible to generate multiple potentially antiviral derivatives. The present invention also relates to a conjugated molecule comprising the CD4-receptor-derived peptide and an organic molecule, preferably the GPR1 peptide or a polyanion. Such a conjugated molecule can in particular be used in antiviral treatments, in particular the treatment of AIDS. The invention also relates to the methods for preparing the activated peptide derived from the CD4 receptor and the conjugated molecule.

Abstract: The invention relates to a library of 298 peptides useful for formulating a novel therapeutic HIV vaccine. The peptide sequences were selected on the basis of calibration of molecular structure properties of HIV-1 or host cell proteins. A mixture of D- and L-amino acids or all D-amino acids are used to synthesize the stereoisomer peptides for the purpose of increasing their stability. The peptides are expected to have the ability to potently inhibit functioning of proteins important for HIV infection. A plural of the peptides are conjugated together with a biocompatible polymer, preferably HPMA to further increase stability and solubility, decrease drug toxicity, and potentially evade multidrug resistance and exert cooperative effect, since some peptides are the ligands for host proteins such as integrin, trombospondin, VEGFR and LEDGF which can bring the therapeutic peptides to the target cells and therefore help disrupt the interactions between the host proteins and the HIV proteins.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z—R??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—, and where the modifying moiety has a maximum number of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 heavy atoms.

Abstract: The invention teaches derivatives of ascomycin and methods of preparing immunogens and other conjugates useful in immunoassays for quantitatively measuring concentrations of tacrolimus in patient specimens. Antibodies produced from the disclosed immunogens capable of binding to tacrolimus with cross-reactivity of no more than 5% with each of 15-O-demethyl tacrolimus, 31-O-demethyl tacrolimus, and 13,31-O-didemethyl tacrolimus, less than 40% with 13-O-demethyl tacrolimus, and less than 1% with cyclosporin, rapamycin, mycophenolic acid, prednisone, hydrocortisol, and prednisolone are described. Further, immunoassays for measuring the concentration of tacrolimus using such antibodies are taught.

Abstract: The present invention provides methods for enhancing the fragmentation of peptides for mass spectrometry by modifying the peptides with a tagging reagent containing a functional group, such as a tertiary amine, having a greater gas-phase basicity than the amide backbone of the peptide. These high gas-phase basicity functional groups are attached to a peptide by reacting the tagging reagent to one or more available carboxylic acid groups of the peptide. Linking these high gas-phase functional groups to the peptides leads to higher charge state ions from electrospray ionization mass spectrometry (ESI-MS), which fragment more extensively during fragmentation techniques, particularly non-ergodic fragmentation techniques such as electron capture dissociation (ECD) and electron transfer dissociation (ETD).

Abstract: This invention relates to a collagen polypeptide comprising a tripeptide motif having the formula (ProYaaGly)n, where Yaa is an O-methylated amino acid residue and “n” is the number of motif repeats. Preferred O-methylated amino acid residues at the Yaa position include (2S,4R)-4-methoxyproline. Other suitable amino acid residues at that position include O-mono or O-di-halogenated methylproline. Also, disclosed is a method of making a synthetic or a semi-synthetic collagen polypeptide molecule having increased stability relative to natural collagen. The strengthened collagen molecules are suitable for use in biomaterials for the medical field or in leather-related products prepared by the tanning industry.

Abstract: The present disclosure relates to novel vascular endothelial growth factor receptor (VEGFR)-binding polypeptides and methods for using these polypeptides to inhibit biological activities mediated by vascular endothelial growth factors (VEGFs). The present disclosure also provides various improvements relating to single domain binding polypeptides.

Abstract: Novel compounds are provided, which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Y, wherein Y is a chemical structure as shown in FIG. 1. Also provided is a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support, using the protected compounds described above.

Abstract: The present invention applications for same. More particularly, the present invention relates to novel aziridine aldehydes and processes for preparing these novel compounds. The invention also relates to aziridine-conjugated amino derivatives, and processes for preparing the same. Pentacyclic compounds may be prepared using the aziridine aldehydes of the present invention, and the invention relates to these compounds and the processes by which they are made. The invention also relates to aziridine-conjugated bioactive molecules, such as amino acids and peptides, and processes for preparing such compounds.

Abstract: The invention provides methods and kits for characterizing the activity of an acetyl transferase or deacetylase. The method involves enzymatically acetylating or deacetylating in vitro a substrate that is a peptide fragment of a full-length polypeptide, and then non-enzymatically acylating the peptide substrate with acyl groups that differ in molecular weight from the enzymatically added or removed acetyl groups. Typically, deuterated acetic anhydride is used to non-enzymatically acylate the substrate. The fully acylated substrate is then characterized by mass spectrometry to determine the amino acid positions of the substrate that are enzymatically acetylated or deacetylated.

Abstract: A palladatepalladium-promoted hydrolytic polypeptide cleavage process which selectively cleaves the polypeptide at a Cys-His cleavage site comprising solubilizing the polypeptide in a reaction mixture comprised of a palladatepalladium promoter dissolved in a high-concentration acidic organic acid solvent.

Abstract: The invention concerns a method for inhibiting angiogenesis or for treating or preventing cancer or cancer metastasis in an individual. The method is based on the administration of an agent capable of counteracting the influence of or for down-regulating the expression of the vascular adhesion protein 1 (VAP-I). The inhibition of the catalytic activity of VAP-I is especially desirable for inhibiting angiogenesis and for treating or preventing of cancer or cancer metastasis.

Abstract: The present disclosure relates to novel vascular endothelial growth factor receptor (VEGFR)-binding polypeptides and methods for using these polypeptides to inhibit biological activities mediated by vascular endothelial growth factors (VEGFs). The present disclosure also provides various improvements relating to single domain binding polypeptides.

Abstract: One aspect of the invention relates to complexes of a radionuclide with various heteroaryl ligands, e.g., imidazolyl and pyridyl ligands, and their use in radiopharmaceuticals for a variety of clinical diagnostic and therapeutic applications. Another aspect of the invention relates to imidazolyl and pyridyl ligands that form a portion of the aforementioned complexes. Methods for the preparation of the radionuclide complexes are also described. Another aspect of the invention relates to imidazolyl and pyridyl ligands based on derivatized lysine, alanine and bis-amino acids for conjugation to small peptides by solid phase synthetic methods. Additionally, the invention relates to methods for imaging regions of a mammal using the complexes of the invention.

Abstract: Based on our identification of a polypeptide (Angiopep-7) that is efficiently transported to cells such as liver, lung, kidney, spleen, and muscle, the invention provides polypeptides, conjugates including the polypeptides, and methods for treating diseases associated with these cell types. Unlike other aprotinin related polypeptides identified herein (including Angiopep-3, Angiopep-4a Angiopep-4b Angiopep-5, and Angiopep-6) which efficiently cross the blood-brain barrier (BBB), Angiopep-7 is not efficiently transported across the BBB.

Abstract: The present invention relates to a cell-penetrating peptide/fluorescence-labeled magnetic nanoparticle complex and the use thereof. More specifically, relates to a cell-penetrating peptide/fluorescence-labeled magnetic nanoparticle complex in which a cell-penetrating peptide is chemically linked to a fluorescence-labeled magnetic nanoparticle, such that fluorescence-labeled magnetic nanoparticle can be stably introduced directly into cells without endocytosis, and a composition for cell imaging containing the complex. The disclosed invention suggests an innovative therapeutic technology which shows high stability, maximizes the effect of imaging diagnosis through optimal targeting and minimizes side effects, unlike existing viral peptide transporters.

Abstract: Pharmaceutical agents, compositions containing the same and methods for their use for enhancing the bioavailability and pharmacological efficacy of therapeutic peptides. The pharmaceutical agents have the formula Carrier-Linker-Peptide Wherein Peptide is a therapeutically active peptide species having the formula aan wherein n is the number of amino acid residues in the peptide and n is 2 to 40, Carrier is benzoyl, phenylacetyl, cinnamoyl, 3-OH-cinnamoyl, 3,4-OH-cinnamoyl, 3,4-dimethoxycinnamoyl, 3,4-methylenedioxycinnamoyl, 3-methoxycinnamoyl, 3,4-diethoxy-cinnamoyl, 3,4,5-trimethoxy-cinnamoyl, t-butoxycarbonyl, benzyloxycarbonyl, pivaloyl, N-9-fluorenylmethoxycarbonyl, fumaroyl and derivatives thereof and Linker is a C6 to C16 lipidic chain or a derivative thereof, an 8-amino-3,6-dioxaoctanoic acid or polymeric derivative thereof, pseudo peptide, or peptide mimic. Methods of use of compositions having the formula Carrier-Peptide wherein Carrier and Peptide are as just defined are also disclosed.

Abstract: The present invention relates to hydrogels and methods for producing and using the same. In particular, some embodiments of the invention relate to hydrogels and methods for patterning the same.

Abstract: A nanostructure composed of a plurality of peptides, each peptide containing at least one aromatic amino acid, whereby one or more of these peptides is end-capping modified, is disclosed. The nanostructure can take a tubular, fibrillar, planar or spherical shape, and can encapsulate, entrap or be coated by other materials. Methods of preparing the nanostructure, and devices and methods utilizing same are also disclosed.

Abstract: Novel conjugates that are capable of inhibiting GSK-3 activity, a process of producing same, pharmaceutical compositions including same and methods of using same in the treatment of GSK-3 mediated conditions are disclosed. Methods of treating affective disorders using GSK-3 inhibitors are further disclosed.

Abstract: The present invention features HCV NS3 protease substrates containing a europium label and a quenching group. The europium label and quenching group are located on different sides of an ester HCV NS3 protease cleavage site. The substrate can be used in a time-resolved fluorescence (TRF) assay to measure HCV protease activity.

Abstract: The invention relates to peptoid reagents that interact preferentially with a pathogenic form of a conformational disease protein as compared to a nonpathogenic form of the conformational disease protein where the peptoid reagent comprises an amino-terminal region, a carboxy-terminal region, and at least one peptoid region between the amino-terminal region and the carboxy-terminal region where the peptoid region comprises 3 to about 30 N-substituted glycines, and optionally one or more amino acids. The invention also relates to methods of using the peptoids in detecting and isolating prions, and in the treatment and prevention of prion-related diseases.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: The present invention relates to gold binding peptides and shape- and size-tunable synthesis of gold nanostructures. The present inventions are very useful for the production of well-designed, gold-based architectures. The size- and shape-specific gold nanostructure materials prepared by the present invention may find use as: highly conductive interconnections for single-electron transistors, catalysts for the oxidation of carbon monoxide; biological and chemical sensors; and as contrasting agents for electron microscopic and medical imaging applications.

Abstract: The present invention relates to methods and materials for killing cancer cells with proteins derived from bacteria. The invention specifically relates to Azurin, Laz, Pa-CARD, and fusion proteins Azu-H.8 and H.8-Azu, and their use in killing leukemia cells and/or ovarian cancer cells.