Abstract: A process for the preparation of a polypeptide designated in the present invention as 1, composed of the following amino acid units in the structure, namely: L-alanine, L-glutamic acid, L-lysine and L-tyrosine randomly arranged in the polypeptide 1, or pharmaceutically acceptable salts thereof, comprising the steps of: (a) polymerization of a mixture of the N-carboxyanhydrides of L-alanine, L-tyrosine, a protected L-glutamate and a protected L-lysine to obtain protected copolymer 6 or salt thereof; (b) deprotection of the protected copolymer 6 (or salt thereof) to produce polypeptide 1 or a pharmaceutically acceptable salt thereof in one single step; (c) separation and purification of the polypeptide 1 (or a pharmaceutically acceptable salt) to obtain a purified polypeptide 1

Abstract: Novel metal binding ligands are disclosed that may be coupled to peptides for use in methods of diagnosis and therapy. Peptides containing the ligands are produced using a method wherein ligand introduction or cyclization can be conducted at any point during the synthesis of the peptide. Such peptide derivatives are readily labeled with radiometals, such as isotopes of rhenium or technetium, while retaining their ability to tightly bind specific peptide receptors.

Abstract: VLSIPS™ manufacturing processes are of increasing commercial importance. The present invention provides methods and compositions for monitoring the efficiency and quality of polymer synthesis in VLSIPS™ arrays. Methods for monitoring polymer synthesis in an array on a substrate are provided. Monoisomeric labels for the labeling of synthetic polymer arrays are provided. Methods and compositions for post-synthetically labeling polymers in polymer arrays are also provided.

Abstract: An process for the reversible modification of membrane interaction of a compound is described. Modification of membrane interaction can be used to facilitate delivery of molecules to cells in vitro and in vivo. The described modifiers, which are used to reversibly inactivate the membrane active compounds, can also be utilized as cross-linkers or to reverse the charge of a molecule.

Abstract: Nonnatural C-linked carbo-?-peptides with robust secondary structures, which involves the synthesis of a new class of ?-peptides called C-linked carbo-?-peptides. The compounds are favorably disposed for the formation of stable helical structures and are useful as biologically active carbo-?-peptides. The new class of ?-peptides have the following formula The new class of ?-peptides are useful as biologically active molecules to disrupt biological interactions of proteins, for molecular design and to synthesize peptide libraries.

Abstract: A peptide factor, its analogs and methods of using such peptide factor derived from murine epidermal growth factor peptide is disclosed wherein the peptide factor is modified to protect it from proteolytic degradation and the peptide binds to laminin receptors.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protecting groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Abstract: Synthetic methods and compounds involving amino amides, peptides and peptidomimetics. Amino amide derivatives are prepared via the one-step three-component reaction of a glyoxamide, an amine, and an organoboron derivative. Conversion of the product to another glyoxamide intermediate allows the iterative use of this chemistry for the synthesis of peptides and peptidomimetics.

Abstract: The invention provides apparatus and methods for determining the nucleotide sequence of target nucleic acids using hybridization to arrays of oligonucleotides. The invention further provides apparatus and methods for identifying the amino acid sequence of peptides that bind to biologically active macromolecules, by specifically binding biologically active macromolecules to arrays of peptides or peptide mimetics.

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: A method of synthesizing a modified therapeutic peptide capable of forming a peptidase-stabilized therapeutic peptide conjugate, the peptide having between 3 and 50 amino acids, is k. In a first step of the method, a therapeutic peptide having a carboxy terminal amino acid and amino terminal amino acid is synthesized. In a second step, pairs of cysteine residues present in the therapeutic peptide are sequentially and selectively oxidized to form disulfide bridges in the therapeutic peptide. In a third step, a protecting group is attached to remaining cysteine residues that do not form disulfide bridges in the therapeutic peptide. Finally, the peptide is coupled to a reactive group capable of reacting with amino groups, hydroxyl groups or thiol groups on a blood component to form a covalent bond therewith.

Abstract: The invention is directed to methods for purifying Troponin I, particularly recombinant Tropnin I produced in a bacterial expression system. Recombinant Tropnin I can be advantageously purified after reversibly protecting the free sulfhydryl groups, e.g., by forming sulfates. In a specific example, Tropnin I reacted with sodium tetrafhionate yielded sulfitolyzed Tropnin I, which was purified by chromatography on an anion exchanger, followed by hydrophobic interaction chromatography. Facile deprotection of the sulfhydryl groups yields a highly purified product ready for refolding.

Abstract: Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an acetate group, an alkyl amide group, an aryl amide group or a hydroxy group.

Abstract: Process for the preparation of the cyclic pentapeptide cyclo(Arg-Gly-Asp-DPhe-NMeVal) by cyclization of a linear pentapeptide selected from the group consisting of H-Arg(Pbf)-Gly-Asp(OBzl)-DPhe-NMeVal-OH, H-Gly-Asp(OBzl)-DPhe-NMeVal-Arg(Pbf)-OH, H-Asp(OBzl)-DPhe-NMeVal-Arg(Pbf)-Gly-OH, H-DPhe-NMeVal-Arg(Pbf)-Gly-Asp(OBzl)-OH or H-NMeVal-Arg(Pbf)-Gly-Asp (OBzl)-DPhe-OH, subsequent protective group removal and, if appropriate, further conversion into its physiologically acceptable salts.

Abstract: A method is described for a method for the regioselective liquid-phase pegylation of GRF, which increases the yield of the GRF-PEG conjugate having 1 PEG molecule covalently bound to the e-amino group of Lys12. This method is characterized in that the reaction is carried out in a structuring solvent, such as trifluorethanol.

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: In this application is described substrates for high-throughput assays of clostridial neurotoxin proteolytic activities. Two types of substrates are described for use in assays for the proteolytic activities of clostridial neurotoxins: (1) modified peptides or proteins that can serve as FRET substrates and (2) modified peptides or proteins that can serve as immobilized substrates. In both types a fluorescent molecules is present in the substrate, eliminating the requirement for the addition of a fluorigenic reagent. The assays described can be readily adapted for use in automated or robotic systems.

Abstract: Polypeptides of A1-Arg-A2-Cys-Tyr-A3-A4-X-A5-A6-Cit Cys-A7 (I) or their salts (wherein A1 is hydrogen or a residue of arginine, lysine, ornithine, citrulline, alanine, or the like; A2 is an aromatic amino acid residue; A3, A4 and A6 are each a residue of arginine, lysine, ornithine, citrulline, or alanine; A5 is a residue of tyrosine, phenylalanine, alanine, naphthylalanine, or citrulline; A7 is a lysine or arginine residue whose carboxyl group may be converted into amido; and X is a residue of D-ornithyl-proline, prolyl-D-ornithine, D-lysylproline, or the like, with the proviso that any one of A1, A3, A4, A5, A6 and A7 is a residue of alanine or the like or that X is citrulline or the like).

Abstract: A method for preparing a solid support material for carrying out a chemical reaction, said method comprising the following steps: (i) reacting an amino functionalised solid material with a carboxylic acid having at least two similarly protected amino groups to form amide bonds between them, (ii) removing protecting groups in a single step, (iii) optionally repeating steps (i) and (ii) one or more times using the product of the preceding step as the amino functionalised solid material, and (iv) connecting a linkage agent to at least some of the free NH2 groups of the product. The method increases the loading capacity of the solid support material. It is particularly useful in connection with peptide synthesis.

Abstract: The invention relates to peptidomimetic compounds with formula wherein Z═CH2 and Y═CH2, or Z═O and Y═O═O, which are novel analogs of glutathion and are inhibitors of glutathione S-transferase, in particular of GST P1-1. Such inhibition has beneficial effects in therapy against cancer. In particular compounds in which R3 is H, R4 is benzyl and R5 is phenyl are stable towards &ggr;GT activity and are selective for GST P1-1.

Abstract: This invention relates generally to dipeptides and tripeptides and to methods for pharmaceutical treatment of mammals using analogs of such dipeptides and tripeptides. More specifically, the invention relates to tripeptides and their analogs, to pharmaceutical compositions containing such dipeptides and tripeptides and to methods of treatment of mammals using such dipeptides and tripeptides. In addition, the invention relates to methods of treatment of mammals using such dipeptides and tripeptides for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm.

Abstract: A process for the preparation of a polypeptide designated in the present invention as 1, composed of the following amino acid units in the structure, namely: L-alanine, L-glutamic acid, L-lysine and L-tyrosine randomly arranged in the polypeptide 1, or pharmaceutically acceptable salts thereof, comprising the steps of:

Abstract: The present invention relates to novel templates useful for generating novel compounds and to compounds produced utilizing the templates. The templates comprise quaternary amino acids that may be linked to solid supports. These templates make possible the production of novel classes of chemical compounds through a plurality of chemical reactions. The templates are advantageous for use in drug discovery regimes.

Abstract: Novel peptide dimers are provided that bind and activate the erythropoietin receptor (EPO-R) or otherwise act as an EPO agonist. The novel compounds have a first peptide chain R1 and a second peptide chain R2, wherein R1 and R2 may be the same or different, and are linked through a linking moiety. R1 is approximately 10 to 40 amino acid residues in length and comprises the sequence X3X4X5GPX6TX7X8X9 (SEQ ID NO: 1) wherein X3 is C or Hoc, X4 is R, H, L or W, X5 is M, F, I or nor-leucine (J), X6 is any one of the 20 genetically coded L-amino acids or J, X7 is W, 1-naphthylalanine (B) or 2-naphthylalanine (U), X8 is D, E, 1, L or V, and X9 is C or Hoc. Similarly, R2 comprises the sequence X′3X′4X′5GPX′6TX′7X′8X′9 (SEQ ID NO: 2) wherein X′3 is C or Hoc, X′4 is R, H, L or W, X′5 is M, F, I or J, X′6 is any one of the 20 genetically coded L-amino acids or J, X′7 is W, B or U, X8′ is D, E, I, L or V, and X′9 is C or Hoc.

Abstract: This invention provides amino acid N-carboxyanhydrides, each of which has an N-acyl substituent on its nitrogen atom, is represented by the following formula (1): readily reacts with nucleophilic reagents such as free amino acids, alcohols, anions or the like, and are intermediates useful for the high-yield production of amino acid derivatives, optically active compounds, peptides, polypeptides and the like useful in many fields lead by the fields of pharmaceuticals and agrochemicals, and also provides a process for the production of the amino acid N-carboxyanhydrides. Further, the present invention also provides a process for the production of diamides, which uses the compounds of the formula (1) and amine derivatives represented by the following formula (7): These diamides can also be suitably used for the production of amino acid derivatives, optically active compounds, peptides, polypeptides and the like.

Abstract: Peptidomimetic azatides and combinatorial oligoazitide libraries are produced by means of a stepwise synthesis. Combinatorial library construction of this new biomimetic polymer provides a means to fabricate global peptidomimetic libraries.

Abstract: Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbonhydrate fragments each linked to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inparts enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from Streptococcus pneumoniae which may be serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F), or Neisseria meningitidis, which may be serotype (A, B, C) W-135 or Y. Such oligosaccharide fragments may be sized from about 2 to about 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, LeY or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule.

Abstract: Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Abstract: Specially designed non-mammalian GnRH analog decapeptides resistant to degradation by the placental enzyme, C-ase-1, or a post-proline peptidase, are disclosed. The GnRH analogs are further defined as analogs of chicken II GnRH or salmon GnRH. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine, D-Trp or other active D amino acids at position 6 and ethylamide, aza-Gly-amide or other Gly amide at position 10. The D-Arg (6)-chicken II GnRH-ethylamide, D-Arg (6)-chicken II GnRH-aza-Gly(10)-amide, the D-Arg (6)-salmon GnRH ethylamide, and D-Arg (6)-salmon GnRH-aza-Gly(10)-amide analogs are also provided, and demonstrate preferential binding to chorionic GnRH, ovarian, endometrial, tubal, uterine, prostate and testicular receptors. Biopotency is greater at the ovary and endometrium than at the pituitary. These non-mammalian GnRH analogs may be used in pharmaceutical preparation, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent.

Abstract: Novel phosphine and phosphine oxide ligands are prepared using polymeric supports. These compounds can be easily cleaved from the support, and along with the corresponding supported compounds, used as ligands in the preparation of novel, metal-complexed catalysts. The ligands are obtained by combinatorial synthesis. A process for preparing coumarin by contacting salicylaldehyde with an acrylate is also provided.

Abstract: The invention relates to peptides which contain N-methylated amino acid units and have improved water solubility. Medicaments in which the peptides according to the invention are contained can be used for the treatment of hormone-dependent tumours and hormone-influenced non-malignant disorders.

Abstract: Disclosed are &bgr;-peptides containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the &agr; and &bgr; carbons of the peptide backbone. The &bgr;-peptides adopt stable helical and sheet structures in both the solid state and in solution. Method of generating combinatorial libraries of peptides containing &bgr;-peptide residues and the libraries formed thereby are disclosed.

Abstract: Cyclic pentapeptides are disclosed having the following formula (I)-Cyclo(-A1-A2-A3-A4-A5-)-wherein A1, A2, A3, A4 and A5 are amino acid residues. The pentapeptide has amino acid residues in positions 1-2-3 to form a &ggr;-turn, and amino acid residues in positions 3-4-5-1 to form a &bgr;-turn in combination with the &ggr;-turn. D-&agr;-amino acid residues are selected for A1, A3, and A5 and L-&agr;-amino acid residues are selected for A2 and A4. Compounds having &ggr;-turns and &bgr;-turns can be synthesized, regardless of the kinds of amino acid residues, and it is possible to synthesize compounds in which desired amino acid residues are introduced into sites of &bgr;-turn and &ggr;-turn based on their importance from the viewpoint of biological activity. The present invention is therefore available for design of compounds having biological activity.

Abstract: Multifunctionalized support resin for the solid phase synthesis of combinatorial libraries is disclosed. The support resin comprises a resin backbone to which is attached a template containing at least two more attachment points which carry mutiple functionalized benzyl-type linkers. Each linker displays differing chemical stability under cleavage conditions so that products can be selectively and sequentially cleaved and separated from the reaction vessel. The linkers are independently different benzyl-type moieties, and each product synthesized on the linkers may have a different chemical structure. The support resin may further comprise an additional linker which is directly attached to the resin backbone. This linker can benzyl-type linkers or other traditional cleavable-linkers. The invention is further directed to a method for the production of mutiple combinatorial libraries in a simultaneous fashion utilizing the above described support resin.

Abstract: Universal solid supports suitable for use synthesizing of oligonucleotides. The solid supports may be used irrespective of the first RNA or DNA nucleotide to be synthesized, and irrespective of the type of monomer reagent used during the synthesis, that is, irrespective of the type of substitution of the phosphate group in the 3′ position or in the 5′ position depending on whether the synthesis is carried out in the 5′ to 3′ or 3′ to 5′ direction. Following synthesis of the oligonucleotide, deprotection of protecting groups and cleavage of the oligonucleotide from the solid support is accomplished with treatment with standard basic media such as NH4OH, NaOH, methylamine.

Abstract: Compounds of the formula are useful in the treatment of various disorders including, but not limited to, cancer (tumor metathesis, tumorgenesis/tumor growth), angiogenesis (as in cancer, diabetic retinopathy, rheumatoid arthritis), restenosis (following balloon angioplasty or stent implantation), inflammation (as in rheumatoid arthritis, psoriasis), bone diseases (osteopenia induced by bone metastases, immobilization and glucocortocoid treatment, periodontal disease, hyperparathyroidism and rheumatoid arthritis), and as antiviral agents. Novel method of making compounds of formula I are also provided.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Abstract: Disclosed is an improved method for preparing an activated carboxylic acid in the form of a pentafluorophenyl ester, an improved method for making a carboxamide from a pentaflourophenyl ester, and a carboxamide and carboxamide library prepared using both of these methods.

Abstract: The invention relates to a method for producing structured, self-organized molecular monolayers of individual molecular species. The invention is preferably used to create solid-phase bonded substance libraries. To this end, a) a substrate (2) suitable for the first monolayer is provided; b) a microstructured polymer mask (1) having openings is applied to the subtrate (2) at least once in a defined direction.

Abstract: A novel method for generating hydroxylamine, hydroxamic acid, hydroxyurea, and hydroxylsulfonamide compounds is disclosed. The method involves the nucleophilic attack of an alkoxyamine on a suitable solid phase support. Techniques of combinatorial chemistry can then be applied to the immobilized alkoxyamine to generate a diverse set of compounds. Cleavage of the compounds from the support yields a library of hydroxylamine or hydroxylamine derivative compounds, which can be screened for biological activity (e.g., inhibition of metalloproteases).

Abstract: Novel peptide analogs derived from the native sequences of CAP37 peptides 20-44 and 23-42, and their use as therapeutics against bacterial infections and diseases caused by bacterial infection. The peptide analog includes a serine or threonine substitution at one of the two cysteine residues at positions 26 and 42. Substitutions of the native peptide are also contemplated.

Abstract: A method of synthesis of a material corresponding to the general formula: R3—X—H characterized in that it comprises a material corresponding to the following general formula: being cleaved as indicated enzymatically or non-enzymatically using acid catalysis in the presence of a nucleophile, wherein: R1 represents a group providing the site for exo-enzyme or acid hydrolysis; R2 represents an intermediate linked to a solid support; R3 represents a carbohydrate, (oligo-)saccharide, (glyco-)peptide, (glyco-)lipid or an organic molecule which is at least one of heterocyclic and aromatic in structure; X represents O, N(H), N(R″), C(O)O, S, C(O)N(H) or C(O)N(R″), R″ being a non-interfering group; and Support represents a solid support.

Abstract: The invention realtes to improved liquid phase processes for the preparation of the 21 residue protein component, (Lys-Leu4)4-Lys, of the pulmonary surfactant KL-4. These process are amenable to large scale synthesis and one process employs a method of saponifying an ester which reduces the inherent racemization of the &agr;-carbon.

Abstract: The invention relates to novel peptides synthesized according a method utilizing the hypusine reagent: wherein: Q1 Q2 and Q3 may be the same or different and are amino protective groups, provided that Q3 is orthogonal to Q1 and Q2; and Z is a hydroxy protective group, as well as improved methods of peptide synthesis wherein the above-described hypusine reagent is employed to prepare novel hypusine-containing peptides.

Abstract: The invention involves the reception of particular nonapeptides by HLA molecules. The nonapeptides are derived from expression products of the MAGE gene family. The resulting complexes are identified by cytolytic T cells. Such recognition may be used in diagnostics, or therapeutically.

Abstract: Embodiments of the present invention generally relate to carrying out organic chemistry on solid supports comprising derivatised functionalities, methods for synthesizing said supports, methods for synthesizing compounds comprising amine groups or N-containing heterocycles using said solid supports, intermediate compounds linked to said supports and uses thereof.

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog either directly or via a bifunctional linker molecule, such as an amino acid, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.

Abstract: This invention provides method and apparatus for performing chemical and biochemical reactions in solution using in situ generated photo-products as reagent or co-reagent. Specifically, the method and apparatus of the present invention have applications in parallel synthesis of molecular sequence arrays on solid surfaces.

Abstract: A method for synthesizing oligonucleotides on a solid substrate. The method provides for the irradiation of a first predefined region of the substrate without irradiation of a second predefined region of the substrate. The irradiation step removes a protecting group therefrom. The substrate is contacted with a first nucleotide to couple the nucleotide to the substrate in the first predefined region. By repeating these steps, an array of diverse oligonucleotides is formed on the substrate.