Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.

Abstract: The present invention is directed to novel dipeptides thereof, represented by the general Formula I: where R1-R3 and AA are defined herein. The present invention relates to the discovery that compounds having Formula I are potent inhibitors of apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.

Abstract: The present invention relates to the field of immunology, and more particularly to the regulation of antibody idiotypes. Provided are compositions and methods for determining and quantitating immunoglobulin germline transcript expression. As disclosed herein, these methods can be used to screen a plurality of candidate agents to identify a candidate agent capable of modulating an immunoglobulin germline transcript. Further, these methods can be used to identify a candidate agent having different modulatory effects on distinct immunoglobulin germline transcripts.

Abstract: N-terminally modified RANTES derivatives are disclosed. The derivatives effectively block the inflammatory effects of RANTES, and are useful for the treatment of asthma, allergic rhinitis, atopic dermatitis, atheroma/atherosclerosis, and rheumatoid arthritis. Additionally, the compounds are useful for the treatment of HIV infection.

Abstract: Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.

Abstract: The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugates comprise a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Abstract: The invention provides peptide derivatives designed to deliver peptides having growth factor inhibitory activity, especially somatostatin analogs, to the retina by sequential metabolism. The peptide derivatives, which comprise a dihydropyridine pyridinium salt-type redox targetor moiety, a bulky lipophilic function and an amino acid/dipeptide/tripeptide spacer, are used in the prevention and treatment of diabetic retinopathy.

Abstract: The invention involves identification of a mechanism of ?-amyloid peptide cytotoxicity, which enables treatment of conditions caused by ?-amyloid peptide aggregates by administration of compounds which antagonize the mechanism of cytotoxicity. The invention includes the identification and isolation of compounds which can antagonize the aggregation of ?-amyloid peptides and the neurotoxic effects of such aggregates. The compounds include isolated peptides which were selected for their ability to form a complex with a ?-amyloid peptide, or are derived from peptides so selected. Methods for treating conditions resulting from neurotoxic ?-amyloid peptide aggregates and pharmaceutical preparations are provided. Also provided are methods for selecting additional compounds which can antagonize the aggregation of ?-amyloid peptides and the neurotoxic effects of such aggregates.

Abstract: Assay methods for determining whether a peptide is likely to be immunogenic are based on a computer modeling of binding to a Class II MHC DR1 receptor. This is confirmed by competitive inhibition binding assays. The peptides are useful for eliciting an immune response for vaccination or the production of antibodies or T-cells.

Abstract: Compounds which inhibit certain activities of amylin but which also act as amylin agonists with respect to other amylin activities are disclosed. Such compounds are useful in treating disturbances in fuel metabolism in mammals, including but not limited to, diabetes, mellitus, including Type I diabetes and Type II diabetes, impaired glucose tolerance, insulin resistance and Syndrome X. The present invention also relates to methods of treating Type I diabetes, beneficially regulating gastrointestinal motility, treating impaired glucose tolerance, treating postprandial hyperglycemia, treating obesity and treating Syndromne X, comprising administration of a therapeutically effective amount of certain compounds, as described herein.

Abstract: The use of azetidinone compounds that are inhibitors of cholesterol absorption as tools for discovering and characterizing proteins involved in trafficking or absorption of cholesterol and/or cholesteryl esters in biological systems is presented. These compounds can serve as tools for competitive binding assays to discover and characterize other chemical agents useful as cholesterol absorption inhibitors. New compounds of the present invention are also highly efficacious inhibitors of cholesterol absorption.

Abstract: This invention provides methods of protein/polypeptide screening based on the provision of libraries of individual proteins/polypeptides, which in turn can be screened for a number of activities, including cell binding and biological activity. Methods for recovering genes encoding such proteins/polypeptides are also provided.

Abstract: S-nitrosohemoglobin (SNO-Hb) can be formed by reaction of Hb with S-nitrosothiol and by other methods described herein which do not result in oxidation of the heme Fe. Other methods can be used which are not specific only for thiol groups, but which nitrosate Hb more extensively, and may produce polynitrosated metHb as a product or intermediate product of the method. SNO-Hb in its various forms and combinations thereof (oxy, deoxy, met; specifically S-nitrosylated, or nitrosated or nitrated to various extents) can be administered to an animal or human where it is desired to oxygenate, to scavenge free radicals, or to release NO+ groups to tissues. Thiols and/or NO donating agents can also be administered to enhance the transfer of NO+ groups. Examples of conditions to be treated by SNO-Hbs or other nitrosated or nitrated forms of Hb include ischemic injury, hypertension, angina, reperfusion injury and inflammation, and disorders characterized by thrombosis.

Abstract: A method for multiplexed detection and quantification of analytes by reacting them with probe molecules attached to specific and identifiable carriers. These carriers can be of different size, shape, color, and composition. Different probe molecules are attached to different types of carriers prior to analysis. After the reaction takes place, the carriers can be automatically analyzed. This invention obviates cumbersome instruments used for the deposition of probe molecules in geometrically defined arrays. In the present invention, the analytes are identified by their association with the defined carrier, and not (or not only) by their position. Moreover, the use of carriers provides a more homogenous and reproducible representation for probe molecules and reaction products than two-dimensional imprinted arrays or DNA chips.

Abstract: Mixtures of chemical compounds are provided having antibacterial and other utility. The mixtures are formed, preferably in solution phase, from the reaction of a purine or pyrimiding heterocyclic scaffold with a set of related chemical substituients, optionally through employment of a tether moiety. Libraries formed in accordance with the invention have utility per se and are articles of commerce. They can be used to screen for pesticides, drugs and other biologically active compounds.

Abstract: The invention provides a new process for the preparation of polypyrrolinones (I) of various sizes which have found to be useful peptidomimetics. One aspect of the invention is a new process utilizing ?-amino-?-substituted-valerolactones as synthons. A second aspect of the invention is a process for the synthesis of polypyrrolinones using solid-phase techniques.

Abstract: Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.

Abstract: Diseases which can be ameliorated by delivery of NO to tissues affected by the disease can be treated by administration of nitrosyl-heme-containing donors of NO, including nitrosylhemoglobin. Nitrosylhemoglobin can be made by the reaction of NO with hemoglobin under certain conditions in which the NO:hemoglobin ratio is critical, and is converted to SNO-Hb under physiological conditions.

Abstract: An effective technique for the high throughput screening of displacers is described. In this technique, potential displacers are employed to displace a biomolecule (e.g., protein) adsorbed on a chromatographic resin in small-scale batch displacement experiments. The amount of protein displaced from a specific resin by a defined concentration of displacer is determined by monitoring the supermatant for the protein. By evaluating the displaced protein rather than the displacer itself, this technique enables a single detection technique (e.g., absorbance, fluorescence, etc.) to be employed for all batch displacement experiments. By monitoring the amount of protein displaced, the effacy of a large number of potential displacers can be rapidly evaluated. The entire experimental procedure can be carried out rapidly and is thus amenable to high throughput parallel screening of molecules possessing a large range of affinities and physico-chemical properties.

Abstract: Peptide sequences capable of binding to insulin and/or insulin-like growth factor receptors with either agonist or antagonist activity and identified from various peptide libraries are disclosed. This invention also identifies at least two different binding sites, which are present on insulin and insulin-like growth factor receptors, and which selectively bind the peptides of this invention. As agonists, certain of the peptides of this invention may be useful for development as therapeutics to supplement or replace endogenous peptide hormones. The antagonists may also be developed as therapeutics.