Abstract: A chemiluminescent assays for the determination of the presence or amount of a biopolymer in bound assays using 1,2-dioxetanes in connection with AttoPhos.TM. as chemiluminescent substrates for enzyme-labeled targets or probes is provided. Further disclosed is a kit for conducting a bioassay for the presence or concentration of a biopolymer comprising a) an enzyme complex; b) a 1,2-dioxetane; and c) AttoPhos.TM..

Abstract: An improved method for determining binding compounds from a mixture of similar compounds, particularly a phage peptide library, is provided. The method comprises contacting a mixture of candidate compounds with a target molecule presented on two or more different substrates.

Abstract: A combinatorial library composition and method for using the library to construct oligomers effective to bind to a selected ligand is disclosed. The library composition includes at least two sets of ar oligomer libraries, each library set having selected oligomer subunit positions filled by known subunits, and other subunit positions containing permutations of subunits. In the selection method, oligomers from each library set are identified, and a new permutation library formed of subunits corresponding to the highest binding affinity oligomers in each library is screened for binding affinity to the selected ligand.

Abstract: A method of detecting substances, if desired in biological fluids, by using detection reactions based on chemiluminescence, wherein a luminophore, preferably having an emission wavelength longer than about 500 nm, is raised from its non-excited state into an excited state by electron transfer due to the detection reaction, and subsequently the radiation emitted by the luminophore when falling back into its non-excited state is measured. The chemiluminescence reaction is based on the oxidative decomposition of optionally substituted oxalates or oxamides, the radiation emitted by the luminophore when falling back into its non-excited state is of longer wavelength than the nonspecific background radiation of the reaction. The luminophore can be accumulated prior to the chemiluminesence reaction. Nonspecific background radiation of the reaction can be quenched.

Abstract: A dry, removable analytical element can be used to detect chemiluminescent signals produced from the reaction of peroxidase and a chemiluminescent detection system. The analytical element contains at least two layers, the outer layer being non-tacky and water-soluble or water-permeable, and used to contact a gel plate or transblotting membrane in which multiple analytes are located. The resulting signal can be recorded using a photosensitive element. Test kits include the various packaged components needed to use the analytical element for analyte detection. Within the element are critical amounts of oxidase and an oxidase substrate for highly sensitive analyte detection.

Abstract: Disclosed is a method of evaluating an anti-proliferative compound by contacting the compound with a Raf and determining its ability to bind to Ras, and methods of inhibiting cell proliferation in an animal by administering a compound which reduces the interaction of Ras with Raf.

Abstract: A chemical moiety is disclosed which comprises a chemical, biochemicals, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organo-metallic compounds. Methods are disclosed for detecting low concentrations of the chemical moiety using chemiluminescent, electrochemiluminescent, and photo-luminescent means. Compounds are disclosed which are useful for labeling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labeled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labeled substances are of particular use in homogeneous binding assays.

Abstract: Provided is a method for reproducible production of cytokeratin antigen immunogen. Cytokeratins from whole carcinoma cells are purified by preparative SDS-PAGE. Bands corresponding to cytokeratins 8, 18, and 19 are eluted from the gel, and these cytokeratins are digested to produce fragments in the size range of 10-50 Kd. The invention also relates to use of these fragments as immunogens for the production of antibodies. Furthermore, the invention relates to an immunochemical test kit to detect cancer of epithelial origin in body fluids. The kit comprises cytokeratin fragments produced by the method of the invention and antibodies to these fragments.

Abstract: A chemiluminescent assay method, compositions, kits and chemiluminescent acridan compounds are described which use a two-step chemiluminescent reaction process. The reaction involves an acridan compound, preferably a derivative of an N-alkylacridan-9-carboxylic acid, which undergoes a reaction with a peroxide compound, a peroxidase enzyme and an enhancer under conditions of time, temperature and pH which permit the accumulation of an intermediate compound, which is subsequently induced to produce a burst of light by raising the pH. The result is generation of very high intensity light from the reaction. The peroxidase enzyme is present alone or linked to a member of a specific binding pair in an immunoassay, DNA probe assay or other assay where the hydrolytic enzyme is bound to a reporter molecule. The method is particularly amenable to automated assays because of the separation of the incubation and light generating steps.

Abstract: Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle.

Abstract: A labeled complex formed by combining a labeling agent with a biological substance, where the labeling agent is a trinucleus dye represented by the general formula (I)' or (II)':ring(Xa)-La-ring(Xb)-Lb-ring(Xc) (I)'?ring(Xa)-La-ring(Xb)-Lb-ring(Xc)!.sup..sym. Y.sup..crclbar.(II)'where the ring(Xa), ring(Xb), and ring(Xc), which mean rings having Xa, Xb, or Xc respectively, are independently a heterocyclic ring having one to three heteroatoms of oxygen, sulfur, nitrogen, or selenium, the heterocyclic ring being unsubstituted or substituted by any of a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted aralkyl group; La and Lb are independently a methine chain composed of one to six substituted or unsubstituted methine linkage, and one of La and Lb may be omitted to link directly the heterocyclic rings; and Y.sup..crclbar. represents an anion.

Abstract: Disclosed and claimed are methods and apparatus for performing a binding assay for an analyte of interest present in a sample based upon measurement of electrochemiluminescence at an electrode. The method uses magnetically responsive particles. The method and apparatus call for a plurality of electromagnets or permanent magnets in north-south orientation for imposing a magnetic field so as to collect the particles.

Abstract: A chemiluminescent assay utilizing a precomplex reagent of a probe comprising an enhancer compound such as a hapten and a conjugate comprising a chemiluminescent signal generating compound. Kits for performing such an chemiluminescent assay are also provided.

Abstract: The present invention provides a process for identifying compounds which bind to a specific target molecule. The process includes the steps of a) generating a first two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of a .sup.15 N-labeled target molecule; b) exposing the labeled target molecule to one or a mixture of chemical compounds; c) generating a second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of the labeled target molecule that has been exposed to one or a mixture of compounds in step (b); and d) comparing said first and second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: A technique for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

Abstract: A chemiluminescent assay method, compositions and kits are described which use a protected phenolic enhancer compound which is deprotected by a hydrolytic enzyme and then enhances a chemiluminescent reaction. The reaction involves an acridan compound, preferably a derivative of an N-alkylacridan-9-carboxylic acid, which is activated to produce light by a peroxide compound and a peroxidase enzyme in the presence of the deprotected enhancer. The result is enhanced generation of light from the reaction. The hydrolytic enzyme is present alone or linked to a member of a specific binding pair in an immunoassay, DNA probe assay or other assay where the hydrolytic enzyme is bound to a reporter molecule.

Abstract: Disclosed in the present application are methods for the identification of favored and suppressed patterns of hydrophobic and nonhydrophobic amino acids in naturally occuring proteins and polypeptides. Methods are disclosed which enable protein structure alteration based on information gained from hydrophobicity pattern analysis.

Abstract: A chemiluminescent method is provided for the analysis of a target. A peroxidase is first bound as a labelling substance to the target by using a target specific binding reagent. The target so labelled is isolated and then reacted with luminol, hydrogen peroxide and an enhancer in an aqueous solvent. The luminescence of light is detected and measured. The aqueous solvent contains at least one protein selected from the group consisting of skim milk and egg albumin. Preferably, the aqueous solvent also contains a non-ionic surfactant such as a polyoxyethylene ether and/or a sugar alcohol such as mannitol.

Abstract: The precision of identification of analyte composition in a sample, where the possible analytes each provide a series of values for characteristic parameters; in particular where the parameters are generated by cross-reaction with specific binding reagents, is enhanced by applying pattern recognition techniques. Samples to be tested are evaluated with respect to each survey parameter to obtain a pattern of parameter values with respect to each analyte at a given concentration. In the case of the use of a panel of specific binding reagents, the samples to be tested are reacted with this panel and the affinities at various analyte concentrations are determined. This results in a databank of "SC profiles" for known concentrations of each analyte. This databank is stored in a computationally accessible form, which then can be matched against SC profiles obtained by testing unknown samples.