Abstract: The invention relates to novel tubulysin conjugates (e.g. of tubulysin A) and the use thereof in the treatment of cancer diseases.

Abstract: Compounds comprising two human GlxI inhibitors covalently linked via a chemical linker are provided, wherein each of said two human GlxI inhibitors, which may be the same or different, is an S-substituted glutathione or an S-substituted glutathione prodrug, wherein said GlxI inhibitors each have a ?-glutamyl amino group, wherein said chemical linker is covalently bound to each GlxI inhibitor via said ?-glutamyl amino group, and wherein said chemical linker has a length of at least 50 Angstroms. Monovalent irreversible inactivators of human GlxI are also provided. An antineoplastic composition is provided, which comprises a compound described above and a pharmaceutically acceptable carrier. In vitro and in vivo methods of preventing or inhibiting the growth and proliferation of neoplastic cells and/or tumors are also provided.

Abstract: The present invention relates to a compound according to Formula (I): A-(L-Y)p, wherein A comprises at least one substantially cell-membrane impermeable pendant group; L comprises any suitable linker and/or spacer group; Y comprises at least one arsenoxide or arsenoxide equivalent; p is an integer from 1 to 10; and the sum total of carbon atoms in A and L together, is greater than 6.

Abstract: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse CDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn IL Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.

Abstract: The present invention is directed to a method of preventing or treating Alzheimer's Disease or of inhibiting accumulation of amyloid-? deposits in a subject by administering to the subject an agent which inhibits interaction between amyloid-? and proteins which chaperone amyloid-? under conditions effective to prevent or treat Alzheimer's Disease in the subject or to inhibit accumulation of amyloid-? deposits in the subject's brain, respectively. Another embodiment of the present invention relates to a method of inhibiting interaction between apolipoprotein E and amyloid-? by administering an agent which blocks interaction of apolipoprotein E and amyloid-? under conditions effect to block such interaction.

Abstract: The present invention relates to compositions and methods for suppressing an immune response, e.g., by inhibiting class II MHC-mediated activation of T cells. The subject compounds and methods may be used to treat or prevent disorders such as rheumatoid arthritis and/or multiple sclerosis.

Abstract: The present invention provides a method for producing modified stable polypeptides introducing at least one non-natural amino acid into the hydrophobic region of the polypeptide. The thermal and chemical stability of such polypeptides is improved compared to those properties of its corresponding wild type proteins. The invention further provides purified leucine zipper and coiled-coil proteins in which the leucine residues have been replaced with 5,5,5-trifluoroleucines, and the modified proteins so produced demonstrate increased thermal and chemical stability compared to their corresponding wild-type natural proteins.

Abstract: The present invention provides novel polypeptides comprising a prion-aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; and methods of making and using the foregoing.

Abstract: The invention provides, in one aspect, compositions for delivering a bioactive metal ion to a mammal, the compositions comprising (a) an effective amount of a source of the bioactive metal ion, (b) a phosphoprotein preparation obtained by partially cross linking a partial hydrolysate of casein or a caseinate, and (c) one or more physiologically acceptable diluents or carriers. Also provided are compositions for remineralising tooth enamel and/or for treating or preventing dental caries, tooth erosion, dentinal hypersensitivity or gingivitis in a mammal, wherein the compositions comprise an effective amount of such a phosphoprotein preparation, in combination with one or more carriers or diluents. In related aspects, the invention provides methods of using such compositions. Also provided are novel phosphoprotein preparations suitable for use in such compositions and methods.

Abstract: The present invention provides preventive and/or therapeutic drugs for cancer and chronic rheumatoid arthritis which contain a peptide having a CXCR4 antagonism, its amide, its ester or its salt. Also, the present invention provides a novel peptide having a CXCR4 antagonism, its amide, its ester and its salt.

Abstract: A novel class of antimicrobial polymeric agents, which include a plurality of amino acid residues, such as positively charged amino acid residues, and at least one hydrophobic residue linking there between. such as an omega-amino-fatty acid residue designed to exert antimicrobial activity while being stable, non-toxic and avoiding development of resistance thereto and a process of preparing same are disclosed. Further disclosed are pharmaceutical compositions containing same and a method of treating medical conditions associated with pathological microorganisms, a medical device, an imaging probe and a food preservative utilizing same. Further disclosed are conjugates of an amino acid residue and a hydrophobic moiety residue and a process of preparing same.

Abstract: The present invention relates to a compound according to Formula (I): A-(L-Y)p, wherein A comprises at least one substantially cell- membrane impermeable pendant group; L comprises any suitable linker and/or spacer group; Y comprises at least one arsenoxide or arsenoxide equivalent; p is an integer from 1 to 10; and the sum total of carbon atoms in A and L together, is greater than 6.

Abstract: The present invention relates to new growth hormone secretagogue receptor 1A (GHS-R 1A) ligands, and pharmaceutical compositions comprising any of the new GHS-R1 A ligands. The ligands are suitable for a wide range of applications, and thus the present invention also relates to use of the GHS-R1 A ligands according to the present invention in the manufacture of a medicament for the treatment of an individual in need thereof. In another aspect, the present invention relates to a method of treatment of an individual in need thereof, comprising administering to said individual one or more of the GHS-R1A ligands disclosed herein, such as e.g. for treatment of cancer cachexia.

Abstract: A method of storing solutions of reduced glutathione for extended periods of time, by dissolving reduced glutathione in an aqueous medium having a pH of between 5.0 and 8.0 to produce a reduced glutathione solution; reducing the temperature of the reduced glutathione solution to a predetermined temperature which is sufficiently low to prevent oxidative dimerization of glutathione without freezing the aqueous medium; and storing the reduced glutathione solution at the predetermined temperature.

Abstract: The present invention relates to p21 derived peptides capable of inhibiting CDK/cyclin complexes, particularly cyclins A or E/CDK2, by modifying the interaction with their substrates. The peptides are derived from a C-terminal region of p21 and display selectivity for cyclin/CDK2 inhibition over cyclin/CDK4 inhibition. Variants of such peptides particularly involving certain alanine replacements are shown to be particularly potent.

Abstract: The invention describes HLA class II binding peptides encoded by the SSX-2 tumor associated gene, as well as nucleic acids encoding such peptides and antibodies relating to the peptides. The peptides stimulate the activity and proliferation of CD4+ T lymphocytes. Methods and products also are provided for diagnosing and treating conditions characterized by expression of the SSX-2 gene.

Abstract: This invention provides isolated peptides comprising a C-terminal fragment of an ARTS protein, isolated nucleotides encoding same, mimetics and small molecule analogues of same, and therapeutic applications comprising administering a peptide, nucleic acid, or mimetic compound of the present invention. This invention also provides isolated complexes comprising a C-terminal fragment of an ARTS protein and either an IAP protein, a Bir3 domain thereof, or a fragment thereof; compounds that bind or interact with same, and use of the compounds in therapeutic applications.

Abstract: Disclosed is a method for purifying teicoplanin A2 comprising: (i) a primary pre-purification step of purifying a filtrate of fermentation broth of a strain using a synthetic adsorbent; (ii) a secondary pre-purification step of purifying the primary pre-purification solution using a cation exchange resin having a high cross-linkage, a catalytic resin or a chelate resin; (iii) a final purification step of purifying the secondary pre-purification solution using a reversed phase resin; and (iv) a powder-forming step. According to the present invention, it is possible to obtain teicoplanin A2 with a higher purity through a relatively simple process without using an excessive amount of an organic solvent.

Abstract: The product of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide having a plasmin peptide substrate of 2-4 amino acids and mono- or di-peptide linkage, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by plasmin. Also disclosed are methods of making and using the prodrug compounds.

Abstract: The present invention relates to compounds comprising modified corticotrophin releasing factor peptide and specifically urocortin and urocortin-related peptides, modified derivatives thereof, and conjugates of such modified peptides and derivatives to serum components, preferably serum proteins or peptides. The compounds and conjugates of the invention comprise a reactive group, which is covalently attached to a modified peptide or derivative, optionally through a linking group. The present invention also provides methods for the covalent attachment of a modified peptide or derivative to a serum protein or peptide to form a conjugate of the invention. The conjugates of the invention preferably exhibit a longer in vivo circulating half-life compared to the corresponding unconjugated peptides. The conjugates of the invention also retain at least some of the biological activity of the unconjugated peptides, and preferably exhibit increased biological activity compared to the unconjugated peptides.

Abstract: The invention provides crystals of N2-(N,N-dimethyl-L-valyl)-N-[(1S,2R)-2-methoxy-4-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[(2-phenylethyl)amino]propyl]-1-pyrrolidinyl]-1-[(S)-1-methylpropyl]-4-oxobutyl]-N-methyl-L-valinamide or salts thereof which possess potent antitumor activity and methods for their preparation.

Abstract: The present invention provides a new use of DP IV-inhibitors. The compounds of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, are useful in treating conditions mediated by DP IV or DP IV-like enzymes, such as immune, autoimmune or central nervous system disorder selected from the group consisting of strokes, tumors, ischemia, Parkinson's disease and migraines. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of multiple sclerosis.

Abstract: Disclosed are compositions and methods for performing an immuno-assay that includes measuring the amount of an isomerised or optically inverted non-collagen protein derived from cartilage.

Abstract: The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4+ T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C—C? loop of the D1 domain; residues 317-323, the C—C? loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

Abstract: The present invention relates to novel anti-hypertensive molecules. The present invention also provides a process for the preparation of novel antihypertensive molecules. The present invention particularly relates to the preparation of novel Angiotensin Converting Enzyme Inhibitors (ACEI) with prolonged activity. ACE inhibitors play an important role in Renin-Angiotensin-Aldosteron system (RAAS) by inhibiting the activity of Angiotensin Converting Enzyme (ACE) and therefore are used to regulate blood pressure. ACE inhibitors synthesized by the process of present invention have a peptide moiety and nonpeptide moiety. ACE inhibitors, synthesized by this present invention, show enhanced bioavailability and fewer side effects.

Abstract: Methods and products for suppressing a class II MHC-restricted immune response in a mammal, or in mammalian cells, are described. The methods depend upon inhibiting invariant chain proteolysis by cathepsin S from class II MHC/invariant chain complexes, thereby reducing the competency of class II MHC molecules for binding antigenic peptides, reducing presentation of antigenic peptides by class II MHC molecules, and suppressing immune responses. The methods may be employed in the treatment of autoimmune diseases, allergic responses, and organ or tissue graft rejection. Pharmaceutical and therapeutic compositions which are peptide-based inhibitors of cathepsin S are also described.

Abstract: Dipeptide derived inhibitors of the ?-secretase enzyme are provided which are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A? peptide in a mammal. The compounds of the invention provide useful methods of treatment by administration of these inhibitors to reduce A? peptide formation and in pharmaceutical compositions.

Abstract: A method is provided for the preparation of compounds of the formula (R1)(R2)NC(?X)S(O)nR3 or (R1)(R2)NC(?X)OS(O)nR3, wherein R1, R2 and R3, X and n have any of the meanings defined in the specification. A method is also provided for the detection and quantitation of compounds of the formula (R1)(R2)NC(?X)OS(O)nR3. A method to link a therapeutic agent to a compound that is conjugated to glutathione is also provided for the purpose of improving the therapeutic properties of the therapeutic agent. Novel compounds, intermediates, pharmaceutical compositions and methods of use are also provided.

Abstract: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn II. Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.

Abstract: The invention presents vaccine formulations comprising highly antigenic epitopes identified within the semi-conserved loop-I of domain III that are capable of eliciting parasite growth inhibitory antibodies. The cyclized or linear peptides can be applied by known adjuvants or be encapsulated by or attached onto the surface of liposomes or virosomes (IRIVs) which serve as human compatible antigen delivery systems. Both cyclized and linear versions of the peptide antigens are surprisingly effective in eliciting immune responses that are cross-reactive with parasite-expressed AMA-1.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: The present invention provides a method of treatment and/or prophylaxis of arthritis in a vertebrate comprising administering to said vertebrate in need of said treatment and/or prophylaxis a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable carrier, diluent or excipient, wherein said compound of formula (I) is defined as: A—(L—Y)p, wherein: A comprises at least one substantially cell-membrane impermeable pendant group; L comprises any suitable linker and/or spacer group; Y comprises at least one arsenoxide or arsenoxide equivalent; p is an integer from 1 to 10; and the sum total of carbon atoms in A and L together, is greater than 6.

Abstract: A dipeptide or tripeptide carrier system for active agent delivery to cells has an N-terminus natural amino acid and an active agent covalently bonded to a side chain of one of the remaining amino acid bases. The system is amenable to formulation as an oral administrant. The active agent being a therapeutic, a fluorescent dye, or contrast agent where the active agent has a molecular weight of less than 500 atomic mass units. An optional linker is provided intermediate between the active agent and the linking side chain.

Abstract: Tuberculosis in an animal is treated by administration of a therapeutically effective amount of an immunomodulator of formula A. In formula (A), n is 1 or 2, R is hydrogen, acyl, alkyl or a peptide fragment, and X is an aromatic or heterocyclic amino acid or a derivative.

Abstract: The invention provides isolated HLA DRB1*15-binding peptides consisting of the amino acid sequence set forth as SEQ ID NO:7 with 0–10 amino acids added to either or both ends of the amino acid sequence set forth as SEQ ID NO:7, and an endosomal targeting signal comprising an endosomal targeting portion of human invariant chain Ii or LAMP-1.

Abstract: The present invention provides crystals of glutathione oxidized n hydrate (wherein n is an integer or a fraction of not less than 0 and less than 8) useful, for example, as final products of, as raw materials for, or as intermediates of health foods, pharmaceuticals, cosmetics or the like, and a process for producing crystals of glutathione oxidized, which comprises a step of crystallizing glutathione oxidized from a mixture of an aqueous solution containing glutathione oxidized and a water-miscible organic solvent and which is suitable for large-scale synthesis or industrialization.

Abstract: Dendrimers comprising a dentritic polypeptide with one dendron having terminal cationic groups and a lipidic anchor, preferably comprising C6-24-alkyl group containing ?-amino acyl groups, preferably joined to the focal group, are used to assist transfection of cells in vitro and in vivo by DNA. The complex of dendrimer and DNA may be used in gene therapy, for instance to delivery clotting factor genes to cells.

Abstract: Method for reducing the level and/or activity of a target protein in a eukaryotic cell via activation of ubiquitination of the target protein wherein the cell is contacted with the compound having a ubiquitination recognition element covalently linked to a target protein binding element. The ubiquitination and recognition element can bind to either the E3 or E2 elements of the ubiquitination system and the target protein binding element is able to bind specifically to the target protein. The target protein binding element has a molecular weight of less than 30,000 and has a binding affinity for the target protein greater than 105M31 1.

Abstract: Peptides derived from amino acids 307 to 356 of the human blood coagulation factor Va are provided. Such peptides comprise: i) a length of between 3 and 50 amino acids, ii) a minimum of 3 contiguous amino acids from the 307–356 heavy chain region of factor Va, excluding peptide segments comprising amino acids 311 to 325 and amino acids 321 to 335, iii) optional additional amino acids at one or both ends of the contiguous amino acids such that the entire peptide is at least 60% identical to a sequence within 307 to 356 of factor Va, and iv) have an IC50 of between 50 nM to 500 ?M for inhibition of prothrombinase. The present invention also provides a pharmaceutical composition comprising one or more prothrombinase-inhibiting peptide segments. The present invention also provides administration of the pharmaceutical composition to human subjects for the purpose of preventing thrombotic disorders.

Abstract: The present invention relates to a compound according to Formula (I): A-(L-Y)p, wherein A comprises at least one substantially cell-membrane impermeable pendant group; L comprises any suitable linker and/or spacer group; Y comprises at least one arsenoxide or arsenoxide equivalent; p is an integer from 1 to 10; and the sum total of carbon atoms in A and L together, is greater than 6.

Abstract: Anticancer peptides which incorporate furanoid sugar amino acids and compositions made using these peptides are described. Methods for synthesis of the peptides and for preparing the furanoid sugar amino acids are disclosed. The peptides and compositions made using the peptides have pharmacological applications of these peptides especially in the treatment and prevention of cancer and tumors.

Abstract: Embodiments relate to the discovery that certain tripeptide amides and glycine amide can be used to inhibit viral infection, including human immunodeficiency virus (HIV) infection. More specifically, medicaments comprising said tripeptide amides and/or glycine amide and methods of using said compounds for the prevention and treatment of viral infection, such as HIV infection, are provided.

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: The invention relates to a compound suitable for inhibiting the influx of polymorphonuclear leukocytes (PMNs) into a tissue involved in a chronic inflammatory disease. The compound according to the invention is capable of forming a complex with N-acetyl-Pro-Gly-Pro. The invention also relates to a method of selecting such a compound, a pharmaceutical composition and an application of the compound.

Abstract: Disclosed are polypeptide compounds containing at least one residue comprising a cyclically-constrained ?-amino acid residue. The compounds have the formula where A is a hydrogen, hydroxy, amino- or carboxy-protecting group, Y is a single bond or a prolyl-containing linking group, and X and Y are ?-amino acid residues, provided that one of X or Y is a conformationally-restrained ?-amino acid residue, and “a,” “c,” and “d” are positive integers. The compounds find use as non-enzymatically degradable probes to mimic protein behavior in solution.

Abstract: The present invention provides a basic amino acid derivative represented by the formula (1): The present invention also provides a method of making a gelled product by employing the aforementioned compound, as well as a gel, perfumery, and/or cosmetic containing the same.

Abstract: Disclosed are ?-peptides and ?-peptide conjugates that are capable of diffusing or otherwise being transported across the cell membranes of living cells. The ?-peptides contain at least six ?-amino acid residues, at leastsix of which are preferably ?3-homoarginine residues. It has been found that when pharmacologically-active agents are conjugated to these types of ?-peptides, the resulting conjugates (also disclosed herein) are also capable of diffusing or otherwise being transported across the cell membranes of living cells, including mammalian cells.

Abstract: It is described a process for preparing, in high yields and purity and without the need of carrying out several steps and/or isolating many intermediates which could lead to undesired by-products, a distamycin derivative of formula wherein R is a bromine or chlorine atom; or a pharmaceutically acceptable salt thereof. The compounds of formula (I) are useful in therapy as antitumor agents.

Abstract: The synthesis of peptides comprising disulphide bridges is challenging since it is difficult to ensure that the correct cysteine residues combine to form the desired disulphide bridges. The present invention describes novel protection techniques useful in the preparation of peptides. Described is a process for the deprotection of an Acm-, MBzl- and/or tBu-protected thiol which comprises reacting said protected thiol with an acid in the presence of an oxidising agent at a temperature sufficient to effect deprotection and generation of disulphide bonds.

Abstract: Fluorinated oligopeptides, especially those having 4,4-difluoro-2-amino butyric acid at the C terminus, may be effective inhibitors of hepatitis C virus NS3 protease. Examples of hexapeptides of the invention, optimized for binding in the S1 specificity pocket of the enzyme, may display IC50s at the sub-micromolar level. Embodiments of tripeptides of the invention, having a keto-acid group at the C-terminus are, likewise, potent inhibitors of NS3 protease.