Abstract: The invention relates to crystalline peptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions. This invention also relates to methods for the preparation of amino acid keto-epoxides. Specifically, allylic ketones are stereoselectively converted to the desired keto epoxides.

Abstract: The present invention is concerned with a novel composition of matter—a cyclic peptide derived from computer modeling studies that modulates the structure and function of the HIV main envelope protein gp120. The compound is capable of binding to the CD4-binding region of gp120 (this defines it as a CD4 mimic), and can be used for the purposes of: (1) controlling and preventing HIV infections, (2) detecting, isolating and purifying gp120. Contrary to examples of prior art that involved CD4 mimics being either small molecules or macromolecules, the present invention is concerned with the class of “large small molecules” that may offer a satisfactory balance between the activity and drug-like properties. Modified variants of the prototype compound that can be reasonably considered its derivatives are also claimed.

Abstract: Described herein are methods for forming two or more dicarba bridges, as well as new compounds containing dicarba bridges.

Abstract: A solvent system which comprises two or more single organic solvents or two or more mixed organic solvents, characterized in that the state of the solvent system can be reversibly changed, with changing temperature conditions, from one state which is a homogeneously compatibilized mixed solvent system in which the two or more single or more mixed organic solvents constituting the solvent system have been homogeneously compatibilized and mixed to the other state which is a separated solvent system made up of two or more separated phases respectively consisting mainly of the two or more single or mixed organic solvents constituting solvent system, and that when the solvent system is the homogeneously mixed solvent system, a chemical component which is soluble in only one of the single or mixed organic solvents can be evenly dissolved in the system; and a process for producing a compound with the solvent system.

Abstract: A nanoparticle-polypeptide complex comprising a bioactive polypeptide in association with a nanoparticle, wherein the bioactive polypeptide is modified by the addition of a chemical moiety that facilitates cellular uptake of the protein. The polypeptide can be a protein or a peptide. In some embodiments, the amino acid sequence of the protein or peptide is derived from the amino acid sequence of a tumor suppressor gene product.

Abstract: The disclosure is directed to methods and compositions that include MNTF peptides and their analogs for cosmetic and dermatological purposes.

Abstract: Methods for analyzing, selecting, characterizing or classifying compositions of a co-polymer, e.g., glatiramer acetate are described. The methods entail analysis of pyro-glutamate in the composition, and, in some methods, comparing the amount of pyro-glutamate present in a composition to a reference standard. In some cases, the methods entail treating the co-polymer with pyro-glutamate aminopeptidase to cleave N-terminal pyro-glutamate residues.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The following invention is directed to macromolecules having controlled stoichiometry and topology, processes for their production, and applications for their use. The macromolecules have a controlled functional moiety stoichiometry and include at least one dendritic motif having a surface layer formed from at least one surface building unit and at least one subsurface layer formed from at least one building unit, the surface building unit and building units having a hydrocarbon backbone bearing a carbonyl group and at least one amine group; and at least two different functional moieties on the building unit and/or surface building unit; where functional moiety stoichiometry refers to the number and type of functional moieties.

Abstract: The present invention relates to novel macrocyclic compounds and methods of treating a hepatitis C infection in a subject in need of such therapy with said macrocyclic compounds. The present invention further relates to pharmaceutical compositions comprising the compounds of the present invention, or pharmaceutically acceptable salts, esters, or prodrugs thereof, in combination with a pharmaceutically acceptable carrier or excipient.

Abstract: The present invention relates to compounds (e.g., peptidomimetics and non-peptides) that treat, prevent, or stabilize cellular proliferative disorders and methods of treating, preventing, or stabilizing such disorders. The invention also provides three-dimensional structures of a human BRCT domain-BACH1 phosphopeptide complex.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

Abstract: An apparatus for forming a surface reservoir to hold a sample for a desirable period of time is described. The apparatus contains a platform, a solid surface disposed onto the platform, and an assembly of a bottomless vessel mounted on the solid surface. Also described is an apparatus that forms an array of surface reservoirs on a solid surface when multiple bottomless vessels are used, which can be used for high throughput applications. The apparatus can be used in applications on a solid surface, such as immunohistochemistry (IHC), oligo synthesis, peptide synthesis, ELISA, DNA array, peptide array, protein array, antibody array, tissue array, cell culturing, etc.

Abstract: This disclosure relates to equipment utilized to manufacture chemical agents, particularly biopharmaceuticals. In some embodiments, reactor systems comprising a mobile carriage assembly; a disposable reaction container removably attached to the carriage assembly; and, a carriage holder into which the mobile carriage assembly may be removably inserted are provided.

Abstract: The present invention provides a peptide degradation reagent with the following characteristics: 1) it has no marked toxicity such as carcinogenicity, 2) it does not produce metastable peaks resulting from excessive degradation property, 3) it does not produce multiply-charged ion peaks which are interference peaks, and 4) it can secure separation and sharpness of peaks. The present invention also provides a method for specifically cleaving N—C? bonds on a peptide backbone using the above-described reagent, and a method of determining the amino acid sequence of a peptide utilizing this specific cleavage. A method for specifically cleaving N—C? bonds on the backbone of a peptide, comprising irradiating the peptide with laser light in the presence of 5-amino salicylic acid. A method for determining the amino acid sequence of a peptide, comprising irradiating the peptide with laser light in the presence of 5-amino salicylic acid to thereby specifically cleave N—C? bonds on the peptide backbone.

Abstract: The present invention identifies biomarkers that are diagnostic of nerve cell injury, organ injury, and/or neuronal disorders. Detection of different biomarkers of the invention are also diagnostic of the degree of severity of nerve injury, the cell(s) involved in the injury, and the subcellular localization of the injury.

Abstract: This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.

Abstract: The present invention provides a clinically usable radiolabeled compound that is precisely directable in vivo to a target tissue. The compound of the present invention has a first polypeptide or an analogue thereof, and a second polypeptide bonded to an N-terminus of the first polypeptide or the analogue thereof. In the compound, the first polypeptide is a polypeptide that specifically binds with a protein expressed in a target tissue, the second polypeptide has an amino acid region that has a high affinity for a radioactive metal nuclide, and the radioactive metal nuclide that has a high affinity for the amino acid region is held in the amino acid region.

Abstract: The present invention relates to treating and preventing pain. More particularly the present invention demonstrates the involvement of K2P potassium channels in the antalgic effect of morphine. The present invention therefore provides a screening method for identifying antalgics.

Abstract: The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: A chemoselective chemical ligation method is disclosed. The method joins two peptide segments efficiently to produce a larger peptide or protein, by generating a natural peptide bond (Xaa-Ser and Xaa-Thr) at the ligation site (Xaa represents any 5 amino acid). The method requires two steps (FIG. 1 (a)): a) reacting the starting peptide(s) to form an acetal intermediate with an acetal group at the ligation site; b) converting said acetal intermediate to a desired peptide or protein with said natural peptide bond.

Abstract: The present invention provides a double-stranded nucleic acid in which at least one nucleic acid strand includes an unnatural base that forms a self-complementary base pair or an unnatural base that forms a base pair with any natural base with substantially the same thermal stability. The present invention also provides a method of hybridizing a first nucleic acid strand with a second nucleic acid strand, wherein the first nucleic acid strand includes an unnatural base that forms a self-complementary base pair or an unnatural base that forms a base pair with any natural base with substantially the same thermal stability, and a method of applying the nucleic acid to SNP detection, a DNA chip, DNA/RNA computing, or an in vitro translation system. The present invention provides a method of introducing an unnatural base into a nucleic acid strand and thereby controlling the thermodynamic stability in hybridization of the nucleic acid strand.

Abstract: The present invention relates to a process for the selective enzymatic hydrolysis of C-terminal esters of peptide substrates in the synthesis of peptides, comprising hydrolysing C-terminal tert-butyl esters using the protease subtilisin. This process is useful in the production of protected or unprotected peptides.

Abstract: Non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides are disclosed. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. The non-natural amino acid polypeptides are further modified post-translationally. The non-natural amino acid polypeptides and modified non-natural amino acid polypeptides have many uses, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The instant invention provides methods and compositions for the treatment and diagnosis of cancer, e.g., cancers characterized by the expression of prostate specific membrane antigen (PSMA).

Abstract: The invention provides high-yield protein dimerization methods using highly reactive bis-thioimidates that may be used in the manufacture of a highly potent anti-cancer peptide dimers.

Abstract: Disclosed are peptide structures that are stable in aqueous and non-aqueous media where a first linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini is joined by at least one turn region to a second linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini. The peptide chains can be joined at the C terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain, a C terminus of one of the linear peptide chains with a C terminus of the other linear peptide chain, or an N terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain.

Abstract: The present invention concerns 2-amino-3-methyl-hex-5-enoic acid, its use for the production of peptides such as bacitracins and a method for producing it.

Abstract: The present invention includes fusion peptides comprising fragments of the cancer-related protein Her2/neu, methods of preparing such fusion peptides, virosomes comprising such fusion peptides, and uses of such fusion peptides or virosomes for the prevention, treatment or amelioration of a cancer characterized by expression or over-expression of the Her2/neu protein.

Abstract: The present invention relates to a product comprising a solid substrate and a moiety of formula (I) linked thereto: wherein X, X? and R are as defined herein. The product is useful for immobilising target molecules such as molecules of biochemical interest to solid substrates for numerous applications, such as affinity chromatography, ELISA, biotechnological assay techniques and solid phase peptide synthesis.

Abstract: Macrocylic compounds having inhibitory activity on the replication of the hepatitis C virus (HCV) of the general formula (I) X is N, CH and where X bears a double bond it is C; R1a and R1b are hydrogen, C3-7cycloalkyl, aryl, Het, C1-6alkoxy, C1-6alkyl optionally substituted with halo, C1-6alkoxy, cyano, polyhaloC1-6alkoxy, C3-7cycloalkyl, aryl, or with Het; or R1a and R1b together with the nitrogen to which they are attached form a 4 to 6 membered heterocyclic ring which may be optionally substituted; Het being a heterocyclic ring; L is a direct bond, —O—, —O—C1-4alkanediyl-, —O—CO—, —O—C(?O)—NR5a— or —O—C(?O)—NR5a—C1-4alkanediyl-; n is 3, 4, 5, or 6; p is 1, or 2; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl, amino, mono- or diC1-6alkylamino; R4 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system

Abstract: The invention relates to the production of ovoproducts containing bioactive peptides from the egg white subjected to enzymatic treatment. Said peptides have an inhibiting activity of the angiotensin converting enzyme (ACE inhibiting activity) in vitro and/or anti-hypertensive activity in rats and/or antioxidant activity. Said ovoproducts, complete hydrolyzates, the fractions thereof with low molecular weight or their constituent peptides could be used as therapeutic substances with ACE inhibiting activity and/or anti-hypertensive activity and/or anti-oxidant activity, either as functional food products, food additives or ingredients or pharmaceutical products for the treatment and/or prevention of hypertension in all its forms in humans or animals and for the treatment and/or prevention of any disorder associated with hypertension in humans or animals.

Abstract: Disclosed is a process for preparing a macrocyclic compound of the formula (I) wherein a hydroxyl-substituted macrocyclic compound of formula (3) is reacted with a sulfonyl-substituted compound of formula QUIN: The compounds of formula (I) are potent active agents for the treatment of hepatitis C virus (HCV) infection.

Abstract: Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins are provided. Aspects of the methods include screening libraries of 20 residue or more L-peptidic compounds for specific binding to 40 residue or more D-target proteins. Once a L-peptidic compound has been identified that specifically binds to the D-target protein, the D-enantiomer of that compound may be produced.

Abstract: The invention relates 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 ?-carbon.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

Abstract: A library of macrocyclic compounds of the formula (I) where part (A) is a bivalent radical, a —(CH2)y— bivalent radical or a covalent bond; where part (B) is a bivalent radical, a —(CH2)z— bivalent radical, or a covalent bond; where part (C) is a bivalent radical, a —(CH2)t- bivalent radical, or a covalent bond; and where part (T) is a -Y-L-Z- radical wherein Y is CH2 or CO, Z is NH or O and L is a bivalent radical. These compounds are useful for carrying out screening assays or as intermediates for the synthesis of other compounds of pharmaceutical interest. A process for their preparation of these compounds in a combinatorial manner, is also disclosed.

Abstract: A novel gene 0193P1E1B (also designated 193P1E1B) and its encoded protein, and variants thereof, are described wherein 193P1E1B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 193P1E1B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 193P1E1B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 193P1E1B can be used in active or passive immunization.

Abstract: The present invention relates to novel complex peptidomimetic products comprising multiple homogeneous or heterogeneous pendant groups that are site-specifically positioned along a linear oligomer or polymer scaffold and methods of making thereof. More specifically, the invention relates to N-substituted glycine peptoid oligomers or peptoids and their use as substrates for azide-alkyne [3+2]-cycloaddition conjugation reactions and subsequent additional rounds of oligomerization and cycloaddition. The methods of the invention may also be used to generate peptoid-peptide hybrid or peptide products comprising multiple homogeneous or heterogeneous pendant groups, which are positioned precisely along the linear oligomer or polymer scaffold.

Abstract: A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.

Abstract: The peptides Ac-D-2Nal-D-4ClPhe-D-3Pal-OH and Boc-D-2Nal-D-4ClPhe-D-3Pal-OH are intermediates useful in the synthesis of LHRH analogs by coupling with suitable heptapeptides, in particular with the heptapeptides P1-Ser(P2)-MMeTry(P3)-D-Lys(Nic)-Leu-Lys(iPr,P4)-Pro-D-AlaNH2 and P1-Ser(P2)-NMeTry(P3)-D-Asn-Leu-Lys(iPr,P4)-Pro-D-AlaNH2.

Abstract: The present invention relates to the synthesis of depsipeptides on solid phase support. Said depsipeptides are then implicated in a solution phase O—N acyl shift enabling to obtain the corresponding peptide alcohols.

Abstract: The invention relates to a method for providing a multispecific peptide ligand comprising a polypeptide covalently linked to a molecular scaffold at three or more amino acid residues and capable of binding to two or more separate targets, comprising the steps of: (a) providing a first repertoire of polypeptides, each polypeptide comprising two or more reactive groups capable of covalent linkage to a molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; (b) providing a second repertoire of polypeptides as described in (a); (c) joining at least one loop of one or more members of the first repertoire to at least one loop of one or more members of the second repertoire to form at least one polypeptide comprising two loops, and (d) conjugating the composite polypeptide(s) to a molecular scaffold at at least three amino acid positions.

Abstract: Disclosed is a method of making peptide structures that are stable in aqueous and non-aqueous media where a first linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini is joined by at least one turn region to a second linear peptide chain comprising alternating D,L- or L,D-amino acids having an N and C termini. The peptide chains can be joined at the C terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain, a C terminus of one of the linear peptide chains with a C terminus of the other linear peptide chain, or an N terminus of one of the linear peptide chains with an N terminus of the other linear peptide chain.

Abstract: The present invention relates to a prodrug comprising at least one cytostatic agent, wherein said prodrug is cleavable by prostate-specific antigen (PSA), a process for preparing said prodrug and a pharmaceutical composition containing said prodrug in a pharmaceutically effective amount, for use in the treatment of cancer.