Abstract: Dye reagents useful in labeling biological materials are provided along with methods for their use.

Abstract: Methods for the selective conjugation of peptides which comprises an enzymatic incorporation of a functional group at the C-terminal end of a peptide followed by reaction with a second compound comprising the moiety to be conjugated to the peptide, wherein said second compound comprises a functional group which selectively reacts with the incorporated functional group.

Abstract: This invention relates to a method of producing a modified (poly)peptide, said method comprising the step of modifying in an organic solvent a crown ether-bound (poly)peptide at one or more carboxylic groups by esterification or thioesterification and/or at the amino group of the N-terminal amino acid by amidation or alkylation. Furthermore provided are (poly)peptides and antibodies obtainable with the method of the invention as well as medical uses thereof.

Abstract: Polyaromatic sodium channel blockers represented by the formula: are provided where the structural variables are defined herein. The invention also includes a variety of compositions, combinations and methods of treatment using these inventive sodium channel blockers.

Abstract: Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and the 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 derivate compounds having one or more benzo nitrogens.

Abstract: The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

Abstract: A pharmacologically active peptide hormone derivative in which the parent peptide hormone has been modified by introducing either a lipophilic substituent, W, in the N-terminal amino acid or a lipophilic substituent, Z, in the C-terminal amino acid of the parent peptide hormone or an analogue thereof, said lipophilic substituent having from 8 to 40 carbon atoms, has a protracted profile of action.

Abstract: The present invention provides a chemically modified human Growth Hormone (hGH) receptor antagonists prepared by attaching a single polyethylene glycol moiety to the N-terminus. The chemically-modified protein according to the present invention have decreased PEGylation heterogeneity and which may also have increased binding affinity.

Abstract: Making a suspended or soluble macromolecular conjugate comprising binding a first macromolecule to a solid via a stable, disruptable bond, stably linking additional macromolecules, and releasing the macromolecular conjugate, as well as macromolecular conjugates prepared by the method.

Abstract: Protein particles are prepared by causing or allowing protein molecules dispersed in a liquid medium at a concentration of 8 mg.mL-1 or greater to react in the presence of a zero-length crosslinker, so as to produce protein particles comprising protein molecules that are covalently bonded together. The protein particles may be produced with sizes in the sub-micron range with closely defined sizes and size distributions. The particles have applications in many fields, but are useful inter alia for the delivery of therapeutic agents and other agents, eg imaging contrast agents, to the body.

Abstract: The present invention relates to compounds of Formula I: wherein variable substituents are defined herein, that modulate the activity of or bind to chemokine receptors such as CCR5. In some embodiments, the compounds of the invention are selective for CCR5. The compounds can be used, for example, to treat diseases associated with chemokine receptor expression or activity such as inflammatory diseases, immune diseases and viral infections.

Abstract: Compounds and methods are provided for the treatment of disease conditions in which modification of serotonergic receptor activity has a beneficial effect. In the method, an effective amount of a compound is administered to a patient in need of such treatment.

Abstract: Disclosed are compounds of formula (I) wherein D1 is a first dye moiety whose fluorescence properties may be modulated so as to be suitable as a donor or an acceptor in an energy transfer arrangement; D2 is a second dye moiety suitable as an acceptor or a donor in an energy transfer arrangement with said first dye; L is a linking group comprises 2-200 linked atoms, wherein said linking group optionally includes an enzyme cleavage site; and M is an enzyme cleavable group chosen to modulate the fluorescence properties of D1. The compounds of formula (I) may be used as reporter molecules for detecting biochemical cleavage events in assays that employ fluorescence resonance energy transfer.

Abstract: Methods and pharmaceutical compositions for regulations of Guanosine- (G-) and/or Guanosine-cytosine-rich (GC-rich) nucleic acid expressions are provided. The methods include a step of interacting the G- and/or GC-rich region of the nucleic acid with thalidomide, and the pharmaceutical compositions include the thalidomide and a pharmaceutical carrier.

Abstract: A method for reducing or substantially preventing formation of a trisulfide derivative of a polypeptide in a liquid medium containing the polypeptide ijn question comprises stripping the liquid medium with a gas, suitably a chemically unreactive gas such as nitrogen or argon.

Abstract: Substituted benzoimidazole compounds useful as anti-infectives that decrease resistance, virulence, or growth of microbes are provided. Methods of making and using substituted benzoimidazole compounds, as well as pharmaceutical preparations thereof, in, e.g., reducing antibiotic resistance and inhibiting biofilms.

Abstract: The present invention provides labeling reagents and methods for labeling primary antibodies and for detecting a target in a sample using an immuno-labeled complex that comprises a target-binding antibody and one or more labeling reagents. The labeling reagents comprise monovalent antibody fragments or non-antibody monomeric proteins whereby the labeling proteins have affinity for a specific region of the target-binding antibody and are covalently attached to a label. Typically, the labeling reagent is an anti-Fc Fab or Fab? fragment that was generated by immunizing a goat or rabbit with the Fc fragment of an antibody.

Abstract: Described herein are compounds that have a spiro structural feature. Also described herein are methods for making such compounds, methods for using such compounds to modulate the activity of steroid hormone nuclear receptors, and pharmaceutical compositions and medicaments comprising such compounds. Also described herein are methods of using such compounds, pharmaceutical compositions and medicaments to treat and/or prevent diseases or conditions associated with the activity of steroid hormone nuclear receptors.

Abstract: An assay for determining compounds that inhibit activity of a BCl-2 protein, or affect conversion of Bcl-2 from an antiapoptotic to a proapoptotic form are described. In addition, compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified.

Abstract: An objective of the present invention is to provide methods for stabilizing proteins and methods for suppressing protein aggregation, which comprise the step of adding for suppressing protein aggregation, which comprise meglumine. Still another objective of the present invention is to provide pharmaceutical compositions comprising antibody molecules stabilized by meglumine, methods for producing the pharmaceutical compositions, and kits comprising the pharmaceutical compositions. To achieve the objectives described above, the present inventors assessed the antibody-stabilizing effect of meglumine, an amino sugar. As a result, the inventors discovered that meglumine was useful as a stabilizer for antibody molecules and also as an excipient for freeze-dried preparations.

Abstract: A polysaccharide derivative having a high solubility in an aqueous solvent is produced. The production method of the present invention uses a compound shown by the general formula (1) as a condensing agent and allows a polysaccharide having a carboxyl group to react with an an organic compound having a functional group capable of condensing with the carboxyl group to prepare the polysaccharide derivative: R1 and R2 independently represent a substituent selected among alkyl groups of 1 to 4 carbon atoms and aryl groups of 6 to 8 carbon atoms; Z?represents a counter anion; and E+represents an organic group shown as: R3, R4, and R5 independently represent an organic group having at least one carbon atom directly bound to a quaternary nitrogen atom and any two or all of R3, R4, and R5 may link together to form a cyclic structure.

Abstract: Naphthalimide compounds are used in tissue bonding and protein cross-linking applications. When activated by an activating agent, such as light in the 400-500 nm absorption range, the naphthalimide compounds form chemically-reactive species that cross-link proteins, bond connective tissues together, and bond tissues and other biomaterials together. A naphthalimide-labeled biomolecule, such as a naphthalimide-labeled chitosan, is also capable of bonding tissues without subsequent direct illumination of the contacted tissue area. The naphthalimide compounds may be used in tissue or arterial repair, stabilization of an expanded arterial wall after angioplasty, tethering pharmaceutical agents to tissue surfaces to provide local drug delivery, and for chemically bonding skin care products, sunscreens, and cosmetics to the skin.

Abstract: This present disclosure relates to compounds of formula (I): The present disclosure also relates to pharmaceutical compositions comprising the compounds of formula (I) and to their methods of use in therapy.

Abstract: The present invention provides boronic acid compounds, boronic esters, and compositions thereof that can modulate apoptosis such as by inhibition of proteasome activity. The compounds and compositions can be used in methods of inducing apoptosis and treating diseases such as cancer and other disorders associated directly or indirectly with proteasome activity.

Abstract: Indirectly labelled assay conjugates prepared by a method that includes the step of submitting the binding member comprised by the conjugate to denaturing conditions prior to labelling the binding member. The indirectly labelled assay conjugates demonstrate an increased sensitivity when employed in diagnostic assays compared to assay conjugates prepared by methods that do not include a step of submitting the binding member to denaturing conditions prior to labelling. Processes for the preparation of the indirectly labelled assay conjugates, methods of detecting an analyte comprising the use of the indirectly labelled assay conjugate and kits comprising the indirectly labelled conjugates are also provided.

Abstract: The present invention relates to a novel class of selective estrogen receptor modulators (SERMs). The SERM compounds are applicable for use in the prevention and/or treatment of a variety of diseases and conditions including prevention and treatment of cancers such as prostate and breast cancer, osteoporosis, hormone-related diseases, hot flashes or vasomotor symptoms, neurological disorders, cardiovascular disease and obesity.

Abstract: The present invention concerns methods for treating or preventing neurological disorders characterized by dysfunction of nicotinic acetylcholine receptors by administering 2,2,6,6-tetramethylpiperidin-4-yl heptanoate (TMPH), or a pharmaceutically acceptable salt thereof, to the patient. In another aspect, the present invention pertains to pharmaceutical compositions containing TMPH, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In another aspect, the present invention pertains to methods for selectively inhibiting nicotinic acetylcholine receptors that lack an ?5, ?6, or ?3 subunit by contacting an effective amount of TMPH, or a pharmaceutically acceptable salt thereof, to the receptor. The method for selectively inhibiting nicotinic acethylcholine receptors that lack an ?5 subunit can be carried out in vivo or in vitro.

Abstract: Substituted indoles of the formula (I) and physiologically acceptable derivatives and salts thereof, in which R1, D, E, R12, p, X1, E, G, X2 and Z are as defined in claim 1, exhibit particular actions on the central nervous system, especially 5HT reuptake-inhibiting and 5 HTx-agonistic and/or -antagonistic actions and in particular serotonin-agonistic and -antagonistic properties and can be employed as antipsychotics, neuroleptics, antidepressants, anxiolyties and/or antihypertonics.

Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.

Abstract: Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

Abstract: The invention provides a method for stably cross-linking a first nucleic acid sequence selected for being stably cross-linked in the presence of a second nucleic acid sequence selected for not being stably cross-linked in a nucleic acid molecule. The method comprises providing a nucleic acid sequence that is complementary to the first nucleic acid sequence; hybridizing the first nucleic acid sequence to its complementary sequence; and stably cross-linking the first nucleic acid sequence to the complementary sequence.

Abstract: The present invention relates to compounds represented by formula (I): where the structural variables are as defined herein. The compounds are useful for promoting hydration of mucosal surfaces.

Abstract: A protein according to the invention can be used to detect or measure calcium ions is provided. Further the protein is useful as a reporter protein or a luminescence marker. A polynucleotide according to the invention is also useful as a reporter gene.

Abstract: Compositions and methods for detecting carbonyl functional groups on polypeptides are disclosed.

Abstract: This invention relates to novel compounds having the structural formula I below: and their pharmaceutically acceptable salts, tautomers or in vivo-hydrolysable precursors, compositions and methods of use thereof, wherein R1, R2, R3, R4, R5, and R6 are defined in the specification. These novel compounds provide a treatment or prophylaxis of anxiety disorders, schizophrenia, cognitive disorders, and/or mood disorders.

Abstract: Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: The present invention relates to compositions and methods for the preparation of modified nucleic acids. In particular, the present invention provides novel reagents and chemistries for the generation of linkers, modified phosphoramidites, and modified solid supports.

Abstract: Reagents and methods are provided for crosslinking and immobilizing biomolecules, drugs and synthetic polymers. The reagents possess (i) a thiol or amino reactive group; and (ii) a hydrazino or oxyamino moiety. Conjugates and immobilized biomolecules are also provided.

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: The present invention provides a method of reducing and/or neutralizing the allergenic protein content of natural rubber latex articles by exposing the natural rubber latex from which the article is made or the final natural rubber latex to an allergenic protein reducing compound. The allergenic protein reducing compounds for use in the present invention fall generally into two classes: (1) cationic compounds and (2) nitrogen-containing compounds. Quaternary ammonium salts are particularly preferred allergenic protein reducing compounds.

Abstract: The invention relates to a carrier-drug conjugate comprising a carrier containing a polypeptide sequence having one or several cysteine radicals and a pharmacon containing a pharmaceutical and/or diagnostic active substance, a spacer molecule and a thiol binding group, whereby over 0.7 mol pharmacon per mol of cysteine radical is bound to the carrier by the thiol binding group. The invention also relates to a method for the production of said conjugate and to medicaments and diagnostic kits containing said conjugate.

Abstract: The present invention provides luminescent lanthanide metal chelates comprising a metal ion of the lanthanide series and a complexing agent comprising at least one phthalamidyl moiety. Also provided are probes incorporating the phthalamidyl ligands of the invention and methods utilizing the ligands of the invention and probes comprising the ligands of the invention.

Abstract: Useful materials are produced from keratin containing raw materials by a process that includes gentle lanthionization of cystine disulfide bonds. Hydratable materials are produced for use in medical and cosmetic applications.

Abstract: The present invention is directed to a therapeutic composition in which human PDGF is bound directly to peptides that self assemble into a biologically compatible gel. When implanted in a patient's body, the composition provides for the slow, sustained release of PDGF. The composition will be especially useful in treating patients who have undergone a myocardial infarction.

Abstract: Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

Abstract: This invention relates to: a labeled amino acid that can be introduced into a protein with the aid of a protein synthesis system; a functional protein having functions derived from a label compound; a labeled amino acid comprising an aromatic ring bound to an amino acid side chain and a label compound bound thereto via the aromatic ring; a functional protein to which the labeled amino acid has been introduced; and a novel method for effectively obtaining a labeled amino acid-tRNA complex.

Abstract: The invention provides a CR2-FH molecule comprising a CR2 portion comprising CR2 protein or a fragment thereof and a FH portion comprising a factor H protein or a fragment thereof, and pharmaceutical compositions comprising a CR2-FH molecule. Also provided are methods of using the compositions for treatment diseases in which the alternative complement pathway is implicated, such as age-related macular degeneration, rheumatoid arthritis, and ischemia reperfusion.

Abstract: Transport molecules include a dendrimer and a biologically active molecule. The dendrimer of such transport molecules includes at least one guanidine group, at least one protonated guanidine group, at least one protected guanidine group, at least one amidine group, at least one protonated amidine group, at least one protected amidine group, at least one ureido group, at least one protonated ureido group, at least one protected ureido group, at least one thioureido group, at least one protonated thioureido group, or at least one protected thioureido group. The biologically active molecule is bonded to the dendrimer. A method of increasing the bioavailability of a drug includes bonding the drug to a dendrimer of the invention.

Abstract: This invention relates to a process for purifying a polypeptide, a capture tag useful for purifying a polypeptide and a periodate-cleavable amino acid derivative useful for purifying a polypeptide. The polypeptide to be purified comprises a vicinal-amino-thiol, vicinal-amino-hydoxyl, vicinal-diol or vicinal-diamino group. The purification process comprises attaching the polypeptide to a purification matrix by contacting the polypeptide with a purification matrix comprising aldehyde or ketone groups under conditions which favor formation of a heterocyclic ring system, washing the purification matrix, and releasing the polypeptide from the purification matrix.

Abstract: Aspects of the present invention include methods of synthesizing phosphocholine analogues and the phosphocholine conjugates formed therefrom and their use in preventing infections caused by microorganisms.