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: 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: 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: 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: 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 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: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: Cyclic peptides and pharmaceutically acceptable salts and esters thereof are provided. The cyclic peptides and pharmaceutically acceptable salts and esters thereof mimic surface features of the C-terminus of endothelin and thereby can be used modulate or alter the activity of the endothelin family of peptides. More particularly, cyclic pentapeptides, cyclic hexapeptides, cyclic heptapeptides and pharmaceutically acceptable derivatives of the peptides that specifically inhibit the activity of endothelin are provided. Among the cyclic peptides are those that have the formula: cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -D-Trp): X.sup.1 is D-Tyr or D-Asp; X.sup.2 is Phe, Ala, Ac.sub.3 c or Pro; X.sup.3 is D-His, D-Ala, D-Val, Gly or .beta.-Ala; and X.sup.4 is His, Ala, .beta.-Ala, Aib, Gly, D-His-gly or Leu; cyclo(X.sup.1 -L-Phe-X.sup.3 -X.sup.4 -X.sup.5) in which X.sup.1 is D-Tyr, D-Asp or D-Glu, X.sup.3 is selected from among D-His, .beta.-Ala-D-His or gly-D-His; X.sup.4 is Ser, Gly or .beta.-Ala, and X.sup.

Abstract: Calcium channel .gamma.-subunit-encoding cDNAs, and related compositions and methods, are provided.

Abstract: DNA fragments and methods for obtaining them are disclosed which when put into mammalian cells together with a dominant marker gene are able to generate functional centromeres. The sequences can be used to form probes for these centromeres. Cell lines containing the functional centromeres are also provided. Methods are taught for isolating mammalian centromeric DNA as well as for producing cell lines carrying an excess of mammalian centromeres linked to a dominant selectable marker gene.

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

Abstract: [DNAs] DNA molecules encoding mammalian calcium channel a.sub.1 and a.sub.2 subunits are provided. The [DNAs] DNA molecules are used to transform host cells which may also contain a reporter gene, the transcription of which is responsive to an ion or molecule capable of entering the cell through a calcium channel.

Abstract: Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: Thiophenyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, isoxazolyl-thiophenyl-sulfonamides, isoxazolyl-furyl-sulfonamides and isoxazolyl-pyrrolyl-sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: A method of rational drug design includes simulating polypeptides in a way that predicts the most probable secondary and/or tertiary structures of a polypeptide, e.g., an oligopeptide, without any presumptions as to the conformation of the underlying primary or secondary structure. The method involves computer simulation of the polypeptide, and more particularly simulating a real-size primary structure in an aqueous environment, shrinking the size of the polypeptide isobarically and isothermally, and expanding the simulated polypeptide to its real size in selected time periods. A useful set of tools, termed Balaji plots, energy conformational maps, and probability maps, assist in identifying those portions of the predicted peptide structure that are most flexible or most rigid. The rational design of novel compounds, useful as drugs, e.g., bioactive peptidomimetic compounds, and constrained analogs thereof, is thus made possible using the simulation methods and tools of the described invention.

Abstract: Sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided. The sulfonamides have formula I: ##STR1## in which Ar.sup.1 is a 3- or 5-isoxazolyl and Ar.sup.2 is selected from among alkyl, including straight and branched chains, aromatic rings, fused aromatic rings and heterocyclic rings, including 5-membered heterocycles with one, two or more heteroatoms and fused ring analogs thereof and 6-membered rings with one, two or more heteroatoms and fused ring analogs thereof. Ar.sup.2 is preferably thiophenyl, furyl, pyrrolyl, naphthyl, and phenyl. Compounds in which Ar.sup.

Abstract: Compounds of formula (I) and pharmaceutical compositions containing the compounds of formula (I): ##STR1## are provided. In formula (I): Ar is a substituted or unsubstituted aromatic or heterocyclic group; R is H or a substituted or unsubstituted straight or branched chain, cyclic or mixture of straight branched and cyclic alkyl, alkenyl, or alkynyl group having from 1-20 carbon atom; A is a functional group that bears a polar moiety; R.sub.1 is R, R--C=0, R substituted with one or more heteroatoms, a substituted or unsubstituted aryl group, or is aryl-(CH.sub.2).sub.n ; R.sub.2 is (CH.sub.2).sub.n, CHR, C(R).sub.2, COO, OCO, NHCO, CONH, SO, SO.sub.2 or NR; R.sub.3 and R.sub.4, which are the same or different or each may be absent, and are .dbd.O, H, O-aryl, OR, O-alkyl or alkyl, aryl, SR, S-aryl, NHR, NH-aryl, NR, or are other heteroaromatic groups; R.sub.5 is H, OH or R; E and F, which are the same or are different, are either N or (CH.sub.2).sub.

Abstract: N-(4-halo-isoxazolyl)sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(4-halo-3-isoxazolyl)sulfonamides and N-(4-halo-5-isoxazolyl)benzenesulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: Methods for covalent attachment of oligonucleotides to solid supports such that substantially all of the oligonucleotides are attached via their 5'-ends are provided. The solid supports with attached oligonucleotides are produced. Thiol-oligonucleotides are attached to bromoacetyl-derivatized polyacrylamide supports, or conversely, bromoacetyl-oligonucleotides are immobilized on thiol-polyacrylamide supports. In a further aspect, bromoacetyl-derivatized oligonucleotides, and polyacrylamide supports with linked oligonucleotides produced by coupling bromoacetyl-derivatized oligonucleotides with thiol-derivatized polyacrylamide solid supports or by coupling thiol-derivatized oligonucleotides with bromoacetyl-derivatized polyacrylamide supports as well as methods for capture of nucleic acids by oligonucleotides attached to polyacrylamide solid supports, either by direct capture or in sandwich hybridization formats are provided.