Abstract: Effector functions are provided to a desired target with improved specificity by use of two or more complementary targeting components. The targeting components assemble a functional moiety at the target. At the target, the functional moiety itself provides an effector function or binds to additional components which provide an effector function. The effector function may be an enzymatic activity, a label or a signal. The binary or polynary targeting system may be used for analyte determination as well.

Abstract: Intracellular translocation of proteins, particularly protein kinase C (PKC) isoenzymes, provides a surrogate test system for determining toxicity of candidate compounds. The profile of translocation with respect to at least one and preferably two or more signal transduction proteins can be correlated with that of known toxins. In addition, databases of such profiles with respect to toxins of various types provide a useful set of standards for evaluating toxicity of candidate compounds. Moreover, to the extent that a toxin's profile mimics that found in a diseased state, the toxin can be used to construct screens for compounds alleviating the disease.

Abstract: Particulate labels that can be individually identified comprise particulate supports to which are bound at least two distinguishable signal generating moieties, such as fluorophores emitting at different wavelengths, which signals are detectable and measurable in situ. By varying the ratio and/or amounts of the signal generating moieties, a multiplicity of different and distinguishable labels is obtained. Each different label can then be coupled to a different reagent and the individual interactions of each reagent with a target observed in parallel.

Abstract: Intermolecular binding can be detected by formation of a “paratope” which results in an immediate generation of a signal. The substances to be tested for interaction are bound to demitopes, wherein said demitopes are components of a paratope which binds a reporter which provides said signal when bound. Known interactions measured in this way can also be employed to screen for compounds which interfere with the interactions. In addition to testing for individual interactions, the interaction of a compound with a library or library×library interactions can also be determined and the effect of potentially interfering substances evaluated.

Abstract: Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent.

Abstract: Methods to identify compounds which have at least one characteristic selected from the group consisting of a composition that

Abstract: Particulate labels that can be individually identified comprise particulate supports to which are bound at least two distinguishable signal-generating moieties, such as fluorophores emitting at different wavelengths, which signals are detectable and measurable in situ. By varying the ratio and/or amounts of the signal-generating moieties, a multiplicity of different and distinguishable labels is obtained. Each different label can then be coupled to a different reagent and the individual interactions of each reagent with a target observed in parallel.

Abstract: An apparatus for high resolution, high throughput, three-dimensional fluorescence microscopy with a rotatable circular disc for mounting samples to be viewed and multiple CCDs and beam splitters as detectors for the fluorescence emission.

Abstract: Modulation of the activity of the insulin receptor, enhancement of glucose uptake by cells, and other effects significant in the control and management of diabetes are accomplished using compounds of the formula 1

Abstract: Improvements in luminescence polarization assays. The improvements may include using confocal optics to increase sensitivity and accuracy, providing additional classes of tracers, providing improved methods to prepare specific luminescent tracers, and/or expanding the scope of assay targets, among others.

Abstract: Modulation of the activity of the insulin receptor, enhancement of glucose uptake by cells, and other effects significant in the control and management of diabetes are accomplished using compounds of the formula wherein each A is independently a proton-accepting substituent; each R is independently a noninterfering substituent; m is 0 or 1; n is 0, 1, or 2; and each linker is independently —NHCNHNH—, —NHCOO—, OCOO—,—CH═CH—, —CH═N—, —CH2CH2—, —NHCH2—, —OCO— or —COO—. Compounds in the genus of Formula (1) can also be used for structure activity studies to identify features responsible for the relevant activities.

Abstract: Particulate labels that can be individually identified comprise particulate supports to which are bound at least two distinguishable signal-generating moieties, such as fluorophores emitting at different wavelengths, which signals are detectable and measurable in situ. By varying the ratio and/or amounts of the signal-generating moieties, a multiplicity of different and distinguishable labels is obtained. Each different label can then be coupled to a different reagent and the individual interactions of each reagent with a target observed in parallel.

Abstract: Particulate labels that can be individually identified comprise particulate supports to which are bound at least two distinguishable signal generating moieties, such as fluorophores emitting at different wavelengths, which signals are detectable and measurable in situ. By varying the ratio and/or amounts of the signal generating moieties, a multiplicity of different and distinguishable labels is obtained. Each different label can then be coupled to a different reagent and the individual interactions of each reagent with a target observed in parallel.

Abstract: A method to follow the uptake of labeled materials into scintillant-marked compartments, cells, tissue and organelles in real time by monitoring the location of scintillant-emitted light is disclosed.

Abstract: Compounds of the formula ##STR1## or the alkyl (1-6C), alkenyl (1-6C), or arylalkyl (7-12C) amides or salts including the cycloamido forms thereof;whereinn is 1 or 2;whereinwhen n is 1, X is a mono- or disubstituted or unsubstituted hydrocarbyl (1-20C) moiety optionally containing 1 or 2 nonadjacent heteroatoms (O, S or N), and wherein said substitution is selected from the group consisting of halo, OR, and SR, wherein R is H or lower alkyl (1-4C); when n is 2, one X is as above defined and the other X is lower alkyl (1-4C);Y is selected from the group consisting of ##STR2## wherein m is 1 or 2; andAA.sub.C is an amino acid coupled through a peptide bond to the remainder of the compound of formula 1, are useful as affinity ligands, elution reagents, solution inhibitors, diagnostic reagents and therapeutics. These compounds and analogous tripeptide glutathione analogs can be used as members of panels to obtain specific characteristic profiles for various glutathione-S-transferases.

Abstract: Compounds of the formula ##STR1## and the esters, amides, amide/esters and salts thereof, wherein YCO is .gamma.-glu or .beta.-asp;G* is phenylglycine or glycine;Z is CH.sub.2, O or S; andX is a hydrocarbon radical selected from C.sub.6 -C.sub.8 alkyl or selected aromatic groupsare useful in modulating hematopoiesis in bone marrow, mitigating the bone-marrow-destructive effects of a chemotherapeutic agent, and in potentiating the toxicity of chemotherapeutic agents.

Abstract: Compounds of the formula ##STR1## or of the formula ##STR2## or the amides, esters or salts thereof, wherein: S.sup.x is S.dbd.O, O.dbd.S.dbd.O, S.dbd.NH, HN.dbd.S.dbd.O, Se.dbd.O, O.dbd.Se.dbd.O, Se.dbd.NH, HN.dbd.Se.dbd.O, S.sup.+ R.sup.3 wherein R.sup.3 is alkyl (1-6C) or O--C.dbd.O or HN--C.dbd.O;each R of R.sup.1, and R.sup.2 is independently H or a noninterfering substituent;wherein (conj) represents a conjugated system capable of transmitting electrons;n is 0 or 1;YCO is selected from the group consisting of .gamma.-Glu, .gamma.-Glu-Gly, Glu, Glu-Gly, .beta.Asp, .beta.-Asp-Gly, Asp and Asp-Gly;AA.sub.C is an amino acid linked through a peptide bond to the remainder of said compound of Formula 1; andN(Z) represents a reduced nitrogen-containing leaving group and L represents an electron-withdrawing leaving group,are useful as prodrugs and to generate active components released by the activity of glutathione S-transferase.

Abstract: Compounds wherein a biologically active molecule is coupled to a glutathione analog through a conjugated system which permits activation of the biologically active molecule while retaining the biologically active molecule tethered to the glutathione analog are useful as tethered prodrugs that slow the rate of clearance of an active biomolecule through the multidrug resistance pump.

Abstract: Modulation of the activity of the insulin receptor, enhancement of glucose uptake by cells, and other effects significant in the control and management of diabetes are accomplished using compounds of the formula ##STR1## whereineach A is independently a proton-accepting substituent;each R is independently a noninterfering substituent;n is 0, 1, or 2; andeach linker is independently an isostere of --NHCONH-- or of --N.dbd.N-- or of --NHCO--.Compounds in the genus of Formula (1) can also be used for structure activity studies to identify features responsible for the relevant activities.

Abstract: Improved methods for determining interactions between peptides or proteins and small molecules are disclosed. The invention methods can be used to screen libraries of either the small molecules or the proteins. In general, the methods comprise contacting an agent/ligand complex consisting essentially of an agent to be tested for binding to a target protein coupled to a ligand capable of binding a proteinaceous ligand-binding domain with a first fusion protein comprising said target protein and a first complementary portion of a segregable protein; and a second fusion protein comprising a proteinaceous ligand-binding domain and a second complementary portion of said segregable protein; and detecting whether the first complementary portion and second complementary portion are brought into proximity.