Abstract: A compound of formula I wherein X represents an optionally halo-substituted (C2-4)alkynylene group bonded via vicinal unsaturated carbon atoms.

Abstract: Methods for identifying compounds that can be used for treatment of neurodegenerative diseases, for monitoring the progression of these diseases, and for monitoring therapeutic intervention of these diseases are provided. These methods are effected by determining the relative amount of .alpha.-sAPP and the ratio of .alpha.-sAPP to total sAPP in body fluids, tissues or in cell culture.

Abstract: Automated drug screening method and a method of studying receptor and ion-channel activity are provided.

Abstract: Isolated DNA encoding each of human calcium channel .alpha..sub.1 -, .alpha..sub.2 -, .beta.- and .gamma.-subunits, including subunits that arise as splice variants of primary transcripts, is provided. Cells and vectors containing the DNA and methods for identifying compounds that modulate the activity of human calcium channels are also provided.

Abstract: Automated assays for detecting and measuring ion channel and cell surface receptor activity and for identifying compounds that modulate or potentiate such activity are provided. Among the assays are fluorescent indicator-based assays that use cells containing effective levels of a fluorescent indicator that is responsive to changes in ion concentration. Activation of the ion channels or receptors is initiated in the automated measurement apparatus by injection into one or more predetermined cell-containing wells of a reagent which is a known or possible activator or inhibitor of the ion channels or receptors of interest. The resulting activity of the ion channels or receptors, which causes changes in ion concentration in the cytoplasm, is determined by measurement of fluorescence intensity changes of the indicator in response to an excitation wavelength.

Abstract: The isolation and characterization of genes involved in proteolytic processing in species of the genus Pichia is described. The availability of such genes has enabled the generation of strains of Pichia which are deficient in proteolytic activity, which strains are useful as hosts for the expression of proteolytically sensitive recombinant products. The isolation and characterization of additional genes from species of the genus Pichia is also described, as well as uses therefore.

Abstract: Methods of use of compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds provided for use in the methods are those of the formula: ##STR1## in which R.sub.1 is preferably 2-methylpropenyl, 2-butenyl, cyclohexyl or cyclohexylmethyl; R.sub.2, R.sub.4, and R.sub.8 are each preferably independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; R.sub.5 is preferably iso-butyl; R.sub.6 is preferably H or methyl; R.sub.7 --(Q).sub.n is preferably benzyloxycarbonyl or acetyl; Q is preferably --C(O)--; and X is preferably an aldehyde, .alpha.-ketoester or .alpha.-ketoamide.

Abstract: In accordance with the present invention, there are provided nucleic acids encoding human NMDA receptor protein subunits and the proteins encoded thereby. The NMDA receptor subunits of the invention comprise components of NMDA receptors that have cation-selective channels and bind glutamate and NMDA. In one aspect of the invention, the nucleic acids encode NMDAR1 and NMDAR2 subunits of human NMDA receptors. In a preferred embodiment, the invention nucleic acids encode NMDAR1, NMDAR2A and NMDAR2C subunits of human NMDA receptors. In addition to being useful for the production of NMDA receptor subunit proteins, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits.

Abstract: DNA encoding human neuronal nicotinic acetylcholine receptor alpha and beta subunits, mammalian and amphibian cells containing said DNA, methods for producing alpha and beta subunits and recombinant (i.e., isolated or substantially pure) alpha subunits (specifically .alpha..sub.4 and .alpha..sub.7) and beta subunits (specifically .beta..sub.4) are provided. In addition, combinations of subunits (i.e., .alpha..sub.1, .alpha..sub.2, .alpha..sub.3, .alpha..sub.4, and/or .alpha..sub.7 subunits in combination with .beta..sub.4 subunits; or .beta..sub.2, .beta..sub.3 and/or .beta..sub.4 subunits in combination with .alpha..sub.4 and/or .alpha..sub.7 subunits) are provided.

Abstract: Methods of use of compounds and compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds are those of formulae (I), (II) and (III): ##STR1## in which R.sub.1 is preferably 2-methyl propene, 2-butene, norleucine; R.sub.2, R.sub.4, and R.sub.8 are each independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; R.sub.5 is preferably iso-butyl; R.sub.6 is H or methyl; R.sub.7 --(Q).sub.n is preferably benzyloxycarbonyl or acetyl; Q is preferably --C(O)--; R.sub.B is preferbly iso-butyl; R.sub.A =--(T).sub.m --(D).sub.m --R.sub.1, is which T is preferably oxygen or carbon, and D is preferably a mono-unsaturated C.sub.3-4 alkenyl being more preferred; and X is an alcohol, particularly a secondary alcohol.

Abstract: Methods of use of compounds and compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided Among the compounds are those of formulae I and II: ##STR1## in which R.sub.1 is preferably 2-methyl propene, 2-butene, cyclohexyl or cyclohexylmethyl; R.sub.2, R.sub.4, and R.sub.8 are each independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; R.sub.5 is preferably iso-butyl; R.sub.6 is H or methyl; R.sub.7 --(Q).sub.n is preferably benzyloxycarbonyl or acetyl; Q is preferably --C(O)--; R.sub.B is preferbly iso-butyl; --R.sub.A =--(T).sub.m --(D).sub.m --R.sub.1, is which T is preferably oxygen or carbon, and D is preferably a mono-unsaturated C.sub.3-4 alkenyl being more preferred; and X is preferably an .alpha.-ketoester or .alpha.-ketoamide or aldehyde.

Abstract: Calcium channel (alpha).sub.1 -subunit and (alpha).sub.2 -subunit-encoding DNA, and related compositions and methods, are provided.

Abstract: In accordance with the present invention, there are provided nucleic acids encoding human metabotropic glutamate receptor subtypes and the proteins encoded thereby. In a particular embodiment, the invention nucleic acids encode mGluR1, mGluR2, mGluR3 and mGluR5 subtypes of human metabotropic glutamate receptors. In addition to being useful for the production of metabotropic glutamate receptor subtypes, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits. In addition to disclosing novel metabotropic glutamate receptor subtypes, the present invention also comprises methods for using such receptor subtypes to identify and characterize compounds which affect the function of such receptors, e.g., agonists, antagonists, and modulators of glutamate receptor function.

Abstract: In accordance with the present invention, there are provided nucleic acids encoding human NMDA receptor protein subunits and the proteins encoded thereby. The NMDA receptor subunits of the invention comprise components of NMDA receptors that have cation-selective channels and bind glutamate and NMDA. In one aspect of the invention, the nucleic acids encode NMDAR1 and NMDAR2 subunits of human NMDA receptors. In a preferred embodiment, the invention nucleic acids encode NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C and NMDAR2D subunits of human NMDA receptors. In addition to being useful for the production of NMDA receptor subunit proteins, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits.

Abstract: Human neuronal nicotinic acetylcholine receptor subunits are described, as are methods for producing cells containing functional receptors employing such subunits. Also described are assay methods for determining the presence of functional HnAChRs in transfected cells, and for determining the agonist or antagonist activity of compounds with respect to such cells.

Abstract: Methods of use of compounds and compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds are those of formulae (I), (II) and (III): ##STR1## in which R.sub.1 is preferably 2-methyl propene, 2-butene, norleucine; R.sub.2, R.sub.4, and R.sub.8 are each independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; R.sub.5 is preferably iso-butyl; R.sub.6 is H or methyl; R.sub.7 --(Q).sub.n is preferably benzyloxycarbonyl or acetyl; Q is preferably --C(O)--; R.sub.B is preferbly iso-butyl; R.sub.A =--(T).sub.m --(D).sub.m --R.sub.1, is which T is preferably oxygen or carbon, and D is preferably a mono-unsaturated C.sub.3-4 alkenyl being more preferred; and X is an alcohol, particularly a secondary alcohol.

Abstract: Methods of use of compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds provided for use in the methods are those of the formula: ##STR1## in which R.sub.1 is preferably 2-methylpropenyl, 2-butenyl, cyclohexyl or cyclohexylmethyl; R.sub.2, R.sub.4, and R.sub.8 are each preferably independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; Q is preferably --C(O)--; R.sub.B is preferably iso-butyl; R.sub.A is --(T).sub.m --(D).sub.m --R.sub.1, in which T is preferably oxygen or NH, m is 0 or 1, and D is preferably C.sub.1-4 alkyl or C.sub.2-4 alkenyl; and X is preferably an aldehyde, .alpha.-ketoester or .alpha.-ketoamide.

Abstract: In accordance with the present invention, there are provided nucleic acids encoding human metabotropic glutamate receptor subtype mGluR6, and the proteins encoded thereby. In addition to being useful for the production of metabotropic glutamate receptor subtype mGluR6, nucleic acids of the invention are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits. In addition to disclosing a novel metabotropic glutamate receptor subtype, mGluR6, the present invention also comprises methods for using the invention receptor subtype to identify and characterize compounds which affect the function of such receptor subtype, e.g., agonists, antagonists, and modulators of glutamate receptor function.

Abstract: Nucleic acid encoding human neuronal nicotinic acetylcholine receptor alpha and beta subunits, mammalian and amphibian cells containing said DNA, methods for producing alpha and beta subunits and recombinant (i.e., isolated or substantially pure) alpha subunits (specifically .alpha..sub.4 and .alpha..sub.7) and beta subunits (specifically .beta..sub.4) are provided. In addition, combinations of subunits (i.e., .alpha..sub.1, .alpha..sub.2, .alpha..sub.3, .alpha..sub.4, and/or .alpha..sub.7 subunits in combination with .beta..sub.4 subunits; or .beta..sub.2, .beta..sub.3 and/or .beta..sub.4 subunits in combination with .alpha..sub.4 and/or .alpha..sub.7 subunits) are provided.

Abstract: Human calcium channel .alpha..sub.1 -, .alpha..sub.2 -, .beta.- and .gamma.-subunit encoding cDNAs, and related compositions and methods, are provided.