Abstract: Cyclic peptides having a random alternation of L-?-aminoacyl residues and aza-?3-aminoacyl residues and their uses.

Abstract: A heparin-binding growth factor (HBGF) analog having two substantially similar sequences (homodimeric sequences) branched from a single amino acid residue, where the sequences are analogs of a particular HBGF that binds to a heparin-binding growth factor receptor (HBGFR), or alternatively that bind to a HBGFR without being an analog of any particular HBGF. The homodimeric sequences may be derived from any portion of a HBGF. The synthetic HBGF analog may be an analog of a hormone, a cytokine, a lymphokine, a chemokine or an interleukin, and may bind to any HBGFR. Further provided are preparations for medical devices, pharmaceutical compositions and methods of using the same.

Abstract: Methods and compositions are described for classifying cells and/or peptides that associate or bind with a particular characteristic pattern to a plurality of cells or cell lines. Aspects of the invention also include the use of peptide(s) having an appropriate binding characteristic to deliver a drug to a cell or cell population.

Abstract: The present invention is directed to methods for treating or preventing Alzheimer's disease by administering therapeutically effective amounts of an agent that reduces Cyclophilin D expression in a patient, or that reduce Cyclophilin D activity or its ability to form a complex with Amyloid beta. Such agents include antisense nucleotides and small interfering RNAs, antibodies that selectively bind to Cyclophilin D, and cyclosporine A and D.

Abstract: Antitumoral compounds of Formula I, and pharmaceutically acceptable salts, derivatives, tautomers, prodrugs or stereoisomers thereof useful as antitumour agents.

Abstract: The present invention relates to a new cyclic peptide compound or a salt thereof, which has anti-hepatitis C virus activities based on inhibitory activity against the RNA replication of hepatitis C virus replicon, to a process for preparation thereof comprising a rearrangement reaction under a mild acidic condition and the following amino acid changing reactions etc., to a pharmaceutical composition comprising the same, and to a method for prophylactic and/or therapeutic treatment of hepatitis C in a human being or an animal.

Abstract: The present invention provides novel glycopeptides antibiotic derivatives. These glycopeptide antibiotic derivatives are characterized in that a sugar residue (I) represented by the formula: (wherein n is an integer of 1 to 5; Sugs are each independently a monosaccharide, (Sug)n is a divalent sugar residue formed by binding of same or different 1 to 5 monosaccharides; RA1 is optionally substituted lower alkyl, optionally substituted lower alkenyl, or optionally substituted cycloalkyl; and RE is OH or NHAc (Ac is acetyl)) is bound to an aromatic ring of the fourth amino acid residue in the glycopeptide skeleton. These derivatives have antibacterial activity against vancomycin-resistant bacteria.

Abstract: A novel cyclic heptapeptide that is useful as a preadipocyte differentiation-inhibitory agent or an adipocyte fat accumulation-inhibitory agent, and the use of such agents, are provided. A novel cyclic heptapeptide represented by the following formula is provided. wherein R is CH3, CH2CH(CH3)2, CH2OCH2C6H5, CH(OH)CH3, or CH2OH.

Abstract: The present invention relates to formulations containing cyclosporin analogs that are structurally similar to cyclosporin A, in particular isomeric mixtures of cyclosporin analogs that are structurally similar to cyclosporin A. The formulations form stable microemulsion preconcentrates and may provide superior drug bioavailability and/or may reduce one or more adverse effects associated with the administration of cyclosporin. Also disclosed are methods for using and preparing the formulations.

Abstract: The embodiments provide compounds of the general Formulae I through general Formula VIII, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract: Derivatives of Maurotoxin (MTX) in which the native disulfide bridge pattern (Cys3-Cys24, Cys9-Cys29, Cys19, Cys31-Cys34) has been disrupted are useful for the treatment of pathologies associated with dysfunctioning and/or activation of Ca2+-activated and/or voltage-gated K+ channel subtypes, such as IKCa1 or Kv1.2. In one group of derivatives, one or two of the amino acid residues of maurotoxin have been replaced by different amino acid residues resulting in the disulfide bridge pattern being changed to Cys3-Cys24, Cys9-Cys29, Cys13-Cys31, Cys19-Cys34. Exemplary substitutions include the Arg residue at position 14 and/or the Lys residue at position 15 replaced by a Gln residue and the Gly residue at position 33 replaced by an Ala residue. Pi1 and HsTx1 derivatives with disrupted native disulfide bridge patterns are similarly useful.

Abstract: The present invention provides constrained peptides and other organic molecules, that mimic the three dimensional characteristics of the HIV-1 V3 loop peptide when bound by a highly potent human neutralizing monoclonal antibody specific for a V3 conformational epitope, which structure is determined by NMR. Methods for screening for, and designing such molecules are disclosed. These molecules are useful as immunogens for inducing broadly-neutralizing antibodies against HIV-1 as well as antagonists for inhibiting the binding of HIV-1 to the relevant co-receptors, and may therefore be used in method of preventing or treating HIV-1 infection and disease.

Abstract: A construct comprising a cancer-homing peptide, an optional linker and a cell-penetrating peptide coupled to an anticancer drug and/or a diagnostic agent is disclosed. The homing peptide is for example a linear pentapeptide such as CREKA (SEQ ID NO:1), AREKA (SEQ 5 ID NO: 23) or CREKA0 (SEQ ID NO: 23), or a cyclic nonapeptide CPGPEGAGC (SEQ ID NO:2), and the cell-penetrating peptide is for example one of the peptides SEQ ID NO:3-SEQ ID NO:20. The anticancer drug may be selected from alkylating agents, antimetabolites and cytotoxic antibiotics, and the diagnostic agent may be a fluorescent label. Further, a method of delivering an anticancer drug and/or a diagnostic agent into a cancer cell 0 comprising administration of a construct according to the invention in vivo or in vitro is described.

Abstract: The present invention is directed to a composition comprising a nanoparticulate cyclosporine having improved bioavailability. The nanoparticulate cyclosporine particles of the composition have an effective average particle size of less than about 2000 nm in diameter and are useful in the prevention and treatment of organ transplant rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, and other related diseases. The invention also relates to a controlled release composition comprising a cyclosporine or a nanoparticulate cyclosporine that in operation delivers the drug in a pulsed or bimodal manner for the prevention and treatment of organ transplant rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, and other related diseases.

Abstract: A subject of the invention is a process for the preparation of the compounds of formula (I): R being as defined in the description as well as their salts, the intermediates, the use of the dihydrochloride as a medicament and the pharmaceutical compositions containing them. The process for preparing formula (I) leads to greater than 50% yield of isomer A, and its intended use, e.g. as an antifungal medicament.

Abstract: More efficient and/or economical methods for synthesizing heptapeptide alcohol analogs of oxytocin are provided along with novel intermediates which are useful in synthesizing such oxytocin analogs. Efficient and economical methods for synthesizing intermediates useful in synthesizing these oxytocin analogs are also provided.

Abstract: Conformationally constrained peptide mimetics in which a hydrogen bond interaction is replaced with a covalent hydrogen bond mimic are provided. Also provided are various methods of making these peptide mimetics.

Abstract: [Problems] To provide an antibacterial agent, particularly a novel polypeptide compound having an antifungal action. [Means for Solution] As a result of an extensive study on a novel antifungal agent, the inventors have found that an excellent anti-deep-fungal activity is exhibited by introducing a cyclohexylmethylamino group or a piperidylmethylamino group as a partial structure of a natural polypeptide compound, and completed the present invention. The compound of the present invention has an excellent antibacterial activity and is therefore useful as an agent for preventing or treating various fungal infections.

Abstract: This invention relates to new peptide-based compounds and their use in therapeutically effective treatments as well as for diagnostic imaging techniques. More specifically the invention relates to the use of such peptide-based compounds used as targeting vectors that bind to receptors associated with angiogenesis, in particular the ?v?3 integrin receptor. Such contrast agents may thus be used for diagnosis of for example malignant diseases, heart diseases, inflammation-related diseases, rheumatoid arthritis and Kaposi's sarcoma. Moreover such compounds may also be used in therapeutic treatment of these diseases.

Abstract: Provided are processes for the preparation and purification of high purity aza cyclohexapeptides.

Abstract: The present invention provides simple, cost effective, rapid, and scalable at industrial scale and provide high purity and yield of Echinocandin-type compounds at low cost as compared to prior art. Moreover the process allows for the removal of impurities by using economical salt-adsorbent complex and provide highly purified Echinocandin type compounds which is highly improved in terms of purity and sufficient for further processing to obtain an active pharmaceutical ingredient such as, the antifungals caspogungin, anidulafungin, and micafungin.

Abstract: Pramlintide, a peptide having the 37 amino acid sequence KCNTATCATQRLANFLVHSSNNFGPILPPT-NVGSNTY-NH2 is prepared via a convergent three-fragment synthesis strategy from the fragments comprising the amino acid residues 1-12, 13-24 and 25-37, respectively.

Abstract: A novel peptides are complexed with HIV-I envelope protein gp120, and causes the protein to assume a CD4i conformation but without occluding the CD4 binding-site of gp120. This peptide-gp120 complex is immunogenic and, upon immunization of subjects, induces broadly-neutralizing antibodies directed to the CD4 binding site of gp120. The peptide preferably consists of a sequence of 8-20 amino acid residues which comprises (a) a core sequence Arg-Xaa1-Asp-Leu-Pro-Xaa2-Trp-Ala (SEQ ID NO: 1) in which Xaa1 and Xaa2 is any amino acid, or (b) certain substitution variants of SEQ ID NO:1.

Abstract: The invention relates to new peptides formed of at least seven subsequent amino acids of the amino acids in position 12-40, counted from the N-terminal end, in the sequence constituting human lactoferrin, and preferably modifications thereof. The invention also relates to medicinal products comprising such peptides, especially intended for treatment and prevention of infections, inflammations and tumours. Furthermore, the invention relates to food stuff, e.g. infant formula food, comprising the above mentioned peptides.

Abstract: The invention relates to methods for the preparation of polypeptides. The polypeptides are prepared in high purity of at least about 98.5%, and preferably at least about 99% by HPLC.

Abstract: The present invention relates to certain biologically active peptides and polypeptides which can be used as therapeutics or prophylactics against diseases or disorders linked to NGF as the causative agent. In one aspect of the present invention, pharmacologically active polypeptides comprising peptides linked to one or more Fc domains are provided.

Abstract: The present invention relates to a process for preparation of a trans ISATX247 compound of the formula: where R1?H or D; R2?H or D; and R3?H or D, by application of organozirconium chemistry. The process involves reacting an acetyl cyclosporin aldehyde with an organozirconium reagent to provide acetyl cyclosporin diene (the acetate of trans ISATX247) and deacetylating the acetyl cyclosporin diene to produce the trans-isomer of ISATX247. The present invention also relates to a process for preparing the same trans ISATX 247 compound, using olefin cross metathesis. The process involves: olefin cross metathesis of acetyl cyclosporin A to afford acetyl cyclosporin ?,?-unsaturated aldehyde; Wittig reaction of the acetyl cyclosporin ?,?-unsaturated aldehyde to provide acetyl cyclosporin diene; and deacetylation of the acetyl cyclosporin diene to produce the trans ISATX247 compound.

Abstract: A method of treatment of inflamed, pre-cancerous or cancerous tissue or polyps in a mammalian subject is disclosed. The treatment involves administration of a composition of at least one peptide agonist of a guanylate cyclase receptor and/or other small molecules that enhance intracellular production of cGMP. The at least one peptide agonist of a guanylate cyclase receptor may be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The inhibitor may be a small molecule, peptide, protein or other compound that inhibits the degradation of cGMP. Without requiring a particular mechanism of action, this treatment may restore a healthy balance between proliferation and apoptosis in the subject's population of epithelial cells, and also suppress carcinogenesis.

Abstract: Devices, compositions, and methods are described which provide a tubular nanostructure targeted to a lipid bilayer membrane. The targeted tubular nanostructure can have a surface region configured to pass through a lipid bilayer membrane of a cell, a hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cellular organelle, and at least one ligand configured to bind one or more cognates on the lipid bilayer membrane of the cellular organelle. The target cell can be, for example, a tumor cell, an infected cell, or a diseased cell in a subject. The tubular nanostructure can form a pore in the lipid bilayer membrane of the cellular organelle, e.g., mitochondria, which can permit transit or translocation of at least one compound across the membrane and cause cell death of the target cell.

Abstract: Disclosed herein are peptides which include an isoDGR motif and which selectively inhibit ?v?3 integrin. In some embodiments, the isoDGR motif results from the deamidation of an NGR motif.

Abstract: Compounds having the Formula I and pharmaceutically acceptable salts thereof are provided in which the variables are described herein. Methods of making the compounds of Formula I are also disclosed.

Abstract: Provided are compounds of the formula (1): wherein R? is hydrogen, methyl or NH2C(O)CH2—; R? and R?? are independently methyl or hydrogen; R adn Ry are independently hydroxy or hydrogen; R1 is hydroxy, hydrogen, or hydroxysulfonyloxy; R7 is hydroxy, hydrogen, hydroxysulfonyloxy or phosphonooxy; R2 is a novel acyl side chain. Also provided are novel formulations, methods of inhibiting fungal and parasitic activity, and a process for preparing dideoxy (R?H) forms of the compounds.

Abstract: Novel peptoid oligomers are disclosed that have a formula represented by the following formula I: The peptoids demonstrate antimicrobial activity and may be prepared as pharmaceutical compositions and used for the prevention or treatment of a variety of conditions in mammals including humans where microbial invasion is involved. The present cyclic and linear peptoids are particularly valuable as their effect is rapid, broad in spectrum and mostly indifferent to resistance provoked by standard antibiotics.

Abstract: The invention relates to nonadepsipeptides and methods for their preparation and their use for the production of medicaments for the treatment and/or prophylaxis of diseases, in particular bacterial infectious diseases.

Abstract: The present invention concerns a chimeric polypeptide, capable of detecting the antibodies generated in rheumatoid arthritis, comprising at least two citrulinated peptide subunits: (i) one derived from the ? or ? chain of the fibrin and (ii) a second derived from the filaggrin. In addition, the invention comprises an antigenic composition, a method and a kit for the diagnosis of rheumatoid arthritis, from the detection of the autoantibodies generated during the course of said disease.

Abstract: This invention relates to methods, compositions, and apparatuses for producing macrocyclic compounds. First, one or more reactants are provided in a reaction medium, which are capable of forming the macrocyclic compound through a desired reaction pathway that includes at least cyclization, and which are further capable of forming undesired oligomers through a undesired reaction pathway that includes undesirable oligomerization. Oligomerization of such reactions in the reaction medium is modulated to reduce formation of undesired oligomers and/or to reduce separation of the undesired oligomers from the reaction medium, relative to a corresponding unmodulated oligomerization reaction, thereby maximizing yields of the macrocyclic compound. The macrocyclic compound so formed is then recovered from the reaction medium. Preferably, the macrocyclic compound spontaneously separates from the reaction medium via phase separation.

Abstract: The present invention relates generally to methods and carriers for cross-linking or immobilising biomolecules such as polypeptides. In particular, the present invention relates to methods and carriers useful for coupling a polypeptide to a carrier via at least one disulphide bond. The carrier coupled to the biomolecules has applications in the fields of e.g. molecular biology, biochemistry, pharmacology, and medical diagnostic technology.

Abstract: The present invention relates generally to receptor-selective variants of the low-density lipoprotein receptor-associated protein (RAP) and compositions thereof, methods of generating such variants and methods of using such receptor-selective RAP variant compositions for therapeutic purposes.

Abstract: The present invention relates generally to tissue differentiation factor (TDF) analogs. More specifically, the invention relates to structure-based methods and compositions useful in designing, identifying, and producing molecules, which act as functional modulators of TDF-like receptors. The invention further relates to methods of detecting, preventing, and treating TDF-associated disorders.

Abstract: The present invention provides cyclosporin analogues of formula I, and compositions comprising these compounds, as well as processes for their preparation, intermediates in their synthesis, and methods of use thereof for prevention of organ transplantation rejection, the treatment of immune disorders and inflammation, and treatment of viral (particularly hepatitis C viral) infection.

Abstract: The invention is based on the discovery that STM/Hop promotes proliferation of human glioblastoma-derived cells but not of normal astrocytes and that the proliferation requires the binding of STM/Hop to PrPC. The invention is directed to methods for treating cancer which rely on interfering with the Hop-PrPC interaction and to peptides, and antibodies raised against the peptides, which directly provide that interference. The invention is further based on the discovery that STI1230-245 peptide and its human homologue Hop23o-245 provide the desired interference with the STI1/Hop-Pre interaction and inhibit the STI 1/Hop-induced proliferation of glioma and glioblastoma cells. The invention is thus further directed to methods of treating cancer that employ these peptides and functional derivatives thereof, and antibodies directed to the peptides and derivatives. The invention is further directed to means of treating cancer which involve reducing the effective amount of Hop or reducing the expression of Hop.

Abstract: The present invention relates to novel ?-AR homologous cyclopeptide-mutants comprising only two cysteine residues able to form an intramolecular linkage, to linear peptides that can form these cyclopeptide-mutants and to nucleic acid molecules encoding these cyclopeptide-mutants and linear peptides. Moreover, vectors and recombinant host cells comprising said nucleic acid molecule and a method for producing the disclosed cyclopeptide-mutants are provided. Further provided is a composition comprising the peptides, nucleic acid molecules, vectors or host cells of the invention. The present invention also relates to therapeutic and diagnostic means, methods and uses taking advantage of the peptides of the invention and to means, methods and uses for detecting anti-?-adrenergic receptor antibodies like anti-?radrenergic receptor antibodies.

Abstract: The present invention relates to various novel substituted dipeptide derived nitrogen-containing heterocyclic compounds, their pharmaceutically acceptable salt derivatives, and their methods of use. In one aspect the present invention relates to compositions and methods for the treatment and prevention of disease in a mammal comprising administering the compounds of the invention in a pharmaceutically acceptable form to a mammal. In particular, the invention relates to medicaments comprising various novel substituted dipeptide derived nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salt derivatives and methods for administration to a mammal for the treatment and prevention of malarial diseases. The compounds of the invention may optionally be administered with at least one pharmaceutically acceptable excipient, another biologically active agent or a combination thereof.

Abstract: The present invention is directed to the use of the peptide compound Cyclo(-Gly-Ile-Cys-Arg-Cys-Ile-Cys-Gly-Arg-Gly-Ile-Cys-Arg-Cys-Ile-Cys-Gly-Arg) as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilisate or liquid buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Cyclo(-Gly-Ile-Cys-Arg-Cys-Ile-Cys-Gly-Arg-Gly-Ile-Cys-Arg-Cys-Ile-Cys-Gly-Arg) optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.

Abstract: An oral cyclosporin composition comprises minicapsules having a core containing a cyclosporin, especially cyclosporin A in a solubilised liquid form. The minicapsules have a release profile to release the pre-solubilised cyclosporin, at least in the colon. The composition may be used for treating a range of intestinal diseases [FIG. 10].

Abstract: The present invention relates to a novel class of diagnostically or therapeutically effective compounds comprising novel peptides able to bind fibrin, to a process for their preparation and to compositions thereof for use in therapy and diagnostics. The compounds of the invention bind, in particular, to fibrin present in the extracellular matrix (EC) of tumor or connective tissue of stroma thus acting as targeting moieties able to bring and successfully bound an active moiety linked thereto to fibrin depositions inside solid tumors.

Abstract: An isolated polypeptide, Z domain, derived from B domain of Staphylococcal protein A, comprising a pair of anti-parallel alpha helices that are capable of binding a target, is provided herein. Introduction of an engineered disulfide bridge between two natural or un-natural amino acids in the polypeptide is provided here. Also provided are methods of using the two-helix binders.

Abstract: A method for treating a subject with multiple sclerosis is disclosed herein. In one embodiment, a method is provided for treating a subject with multiple sclerosis that includes administering to the subject a therapeutically effective amount of a cyclosporin compound.

Abstract: In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snfl-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin.

Abstract: A process and device for the precipitation of an organic compound comprising the steps: (a) providing a first stream comprising an organic compound and a solvent for the organic compound; (b) providing a second stream comprising an anti-solvent for the organic compound; (c) providing a third stream comprising a second stabilising agent; (d) intermixing the first and second streams to form a precipitate of the organic compound in particulate form; and (e) following step (d), intermixing the third stream with the intermixed first and second streams containing the precipitated organic compound in particulate form wherein the first and/or the second stream comprises a first stabilising agent.