Abstract: Provided are peptidomimetic protein-binding arrays, their manufacture, use, and application. The protein-binding array elements of the invention include a peptidomimetic segment linked to a solid support via a stable anchor. The invention contemplates peptidomimetic array element library synthesis, distribution, and spotting of array elements onto solid planar substrates, labeling of complex protein mixtures, and the analysis of differential protein binding to the array. The invention also enables the enrichment or purification, and subsequent sequencing or structural analysis of proteins that are identified as differential by the array screen. Kits including proteomic microarrays in accordance with the present invention are also provided.

Abstract: Provided are protein microarrays, their manufacture, use, and application. Protein microarrays in accordance with the present invention are useful in a variety preoteomic analyses. Various protein arrays in accordance with the present invention may immobilize large arrays of proteins that may be useful for studying protein-protein interactions to improve understanding of disease processes, facilitating drug discovery, or for identifying potential antigens for vaccine development. The protein array elements of the invention are native or modified proteins (e.g., antibodies or fusion proteins). The protein array elements may be attached directly to a organic functionalized mirrored substrate by a binding reaction between functional groups on the substrate (e.g., amine) and protein (e.g., activated carboxylic acid). Techniques for chemical blocking of the arrays are also provided.

Abstract: Molecules having potential biological activity, particularly peptoids, that are conjugated to solid phase supports, spacer groups, and/or ligation moieties, and methods of their preparation, are described. In some instances, the molecules of the invention are made entirely by solid phase synthesis. In other instances, the spacer groups are hydrophilic and compositions containing them, and to solid phase synthesis of varied structure peptoids using chemoselective ligation moieties.

Abstract: This invention relates compositions and methods for increasing the uptake of polynucleotides into cells. Specifically, the invention relates to vectors, targeting ligands, and polycationic agents. The polycationic agents are capable of (1) increasing the frequency of uptake of polynucleotides into a cell, (2) condensing polynucleotides; and (3) inhibiting serum and/or nuclease degradation of polynucleotides.

Abstract: Different-sequence peptoids, including lipid- and sterol-conjugated peptoids, are found to be effective in transfection of cells with oligonucleotides. Combinatorial libraries of such peptoids can be screened efficiently in a high-throughput format, and selected peptoids are identified post-screening.

Abstract: An automated solid-phase method for the synthesis of poly (N-substituted glycines) (referred to herein as poly NSGs) taught here can be used to obtain poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side chain substituents. Each N-substituted glycine monomer is assembled from two “sub-monomers” directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a resin-bound secondary amine with an agent such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the halogen (as a resin-bound &agr;-haloacetamide) with an excess of primary amine. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology, as presented here, makes these polymers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of N-substituted glycines (i.e.

Abstract: Provided are peptidomimetic protein-binding arrays, their manufacture, use, and application. The protein-binding array elements of the invention include a peptidomimetic segment linked to a solid support via a stable anchor. The invention contemplates peptidomimetic array element library synthesis, distribution, and spotting of array elements onto solid planar substrates, labeling of complex protein mixtures, and the analysis of differential protein binding to the array. The invention also enables the enrichment or purification, and subsequent sequencing or structural analysis of proteins that are identified as differential by the array screen. Kits including proteomic microarrays in accordance with the present invention are also provided.

Abstract: Chimeric oligonucleotide of the formula 5′-W-X1-Y-X2-Z-3′, where W represents a 5′-O-alkyl nucleotide, each of X1 and X2 represents a block of seven to twelve phosphodiester-linked 2′-O-alkyl ribonucleotides, Y represents a block of five to twelve phosphorothioate-linked deoxyribonucleotides, and Z represents a blocking group effective to block nuclease activity at the 3′ end of the oligonucleotide, are described. These compounds exhibit high resistance to endo- and exonucleases, high sequence specificity, and the ability to activate RNAse H, as evidenced by efficient and long-lasting suppression of target mRNA.

Abstract: This invention relates compositions and methods for increasing the uptake of polynucleotides into cells. Specifically, the invention relates to vectors, targeting ligands, and polycationic agents. The polycationic agents are capable of (1) increasing the frequency of uptake of polynucleotides into a cell, (2) condensing polynucleotides; and (3) inhibiting serum and/or nuclease degradation of polynucleotides.

Abstract: In accordance with the present invention, there are provided lipid-conjugated polyamide compounds and related compositions and methods thereof. Lipid-conjugated polyamide compounds of the present invention are particularly useful as vehicles for delivering biologically active agents to a target site. In particular, the invention compounds are effective at facilitating the delivery of polynucleotides to cells. The present invention also provides a method for producing stable formulations of polynucleotides complexed with a delivery vehicle.

Abstract: An apparatus is provided for conducting solid phase oligomer synthesis. The apparatus includes a reaction vessel in which a solid phase support is contained. The reaction vessel has a top opening through which gases and solvents can be delivered by way of a series of conduits and valves. The reaction vessel is interconnected through a bottom opening therein and through a series of conduits and valves with a vessel or series of vessels containing a reagent or series of reagents, respectively, required for the synthetic reaction. The reagent vessel serves a both a source of reagent delivered to the reaction vessel and as a repository for unused reagent returned thereto from the reaction vessel. Reagent delivery and mixing is gas-driven using an associated source of an inert gas.

Abstract: A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two "sub-monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a solid support-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like.

Abstract: Method and apparatus for synthesizing biopolymers, such as polypeptides and polynucleotides. The apparatus includes plural reaction vessels in which subunit coupling to biopolymers in a particle suspension is carried out. The vessels are connected to common valving structure for use in mixing the suspension and removing suspension liquid. In one embodiment, a robotic arm in the apparatus is operable to transfer reaction solution to the reaction vessels, and to transfer particle suspensions from the reaction vessels to a mixing vessel and back to the reaction vessels. The method can be used to produce preferably equi-molar amounts of different-sequence biopolymers, such as polypeptides and polynucleotides.

Abstract: Method and apparatus for synthesizing biopolymers, such as polypeptides and polynucleotides. The apparatus includes plural reaction vessels in which subunit coupling to biopolymers in a particle suspension is carried out. The vessels are connected to common valving structure for use in mixing the suspension and removing suspension liquid. In one embodiment, a robotic arm in the apparatus is operable to transfer reaction solution to the reaction vessels, and to transfer particle suspensions from the reaction vessels to a mixing vessel and back to the reaction vessels. The method can be used to produce preferably equi-molar amounts of different-sequence biopolymers, such as polypeptides and polynucleotides.

Abstract: Compounds of Formula 1 bind opioid receptors: which binds to the opioid receptor: ##STR1##

Abstract: Compounds of Formula 1 bind opioid receptors: ##STR1## wherein X and Y are each independently ##STR2##

Abstract: Compounds of Formula 1 bind to the opioid receptors: ##STR1## wherein R.sub.1 is a group of the formula ##STR2## where W is --(CH.sub.2).sub.a -- (where a is 0, 1, or 2), --O--, --NH--, --S--, --SO--, or --SO.sub.2 --, and Ar is phenyl, phenyl-alkyl, phenyl substituted with 1-3 halo, nitro, lower alkyl, hydroxy, amino, alkylamino, dialkylamino, and/or hydroxy-lower alkyl groups, and n is 0, 1, 2, 3, or 4;R.sub.2 and R.sub.3 are each independently H, lower alkyl, or ##STR3## where X is H, OH, lower alkyl, or lower alkoxy, and p is 0, 1, 2, or 3; R.sub.4 is ##STR4## where m is 0, 1, 2, or 3, and R is 1-3 halo, nitro, lower alkyl, hydroxy, amino, alkylamino, dialkylamino, and/or hydroxy-lower alkyl groups;R.sub.5 is cycloalkyl, bicycloalkyl, or tricycloalkyl; andR.sub.6, R.sub.7, R.sub.8, and R.sub.9 are each independently H or lower alkyl.

Abstract: Compounds of Formula 1 bind opioid receptors: which binds to the opioid receptor: ##STR1##

Abstract: Compounds of the formula: ##STR1## are useful for treating conditions modulated by .alpha..sub.1 -adrenergic receptors.

Abstract: Compounds of the formula: ##STR1## are useful for treating conditions modulated by .alpha..sub.1 -adrenergic receptors.